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125 articles found

T0050 – Local motions in L-iditol glass: Identifying different types of secondary relaxations

The sub-Tg relaxations in amorphous L-iditol have been studied by Thermally Stimulated Depolarisation Current (TSDC). The effect of aging on these motional processes was analyzed during annealing at 253K and 243K, respectively 19K and 29K below its calorimetric glass tranaition at Tg=272K.
Joaquim J. Moura Ramos, Herminio P. Diogo, Susanna S. Pinto, Thermochimica Acta 467 (2008) 107-112

T0049 – The nature of crystal disorder in milled pharmaceutical materials

The purpose of this study was to study the nature of disorder in milled crystalline materials. Specifically to elucidate if the induced disorder represents crystal defects or amorphous regions. Felodipine and griseofulvin were chosen as model drugs and subjected to milling. Cryomilling was chosen in order to mitigate the influence of heat generated by the process. Amorphous drug samples were produced by quenching the melt. Crystalline, amorphous and cryomilled drug samples were characterized by powder X-ray diffraction (PXRD), thermal analysis (DSC), thermal polarization (thermally stimulated polarization current), and surface energy (inverse gas chromatography). The PXRD analysis shows that cryomilling reduces the crystallinity of the two drugs, while maintaining the same crystal form. Heat capacity measurements (DSC) show that milled material for either drug does not exhibit a glass transition but shows instead an exothermic (crystallization like) event. The thermal polarization profiles revealed that none of the modes of molecular motion (polarization peaks) characteristic of the amorphous formwere observed in either the unmilled crystalline or milled forms for either drug. For each drug, the polarization spectra of milled forms were similar, but not identical, to those of the corresponding unmilled crystalline materials. Inverse gas chromatography (IGC) measurements showed that the surface energy of cryomilled samples was higher than those of the unmilled and amorphous forms for both drugs. The polarization and heat capacity measurements show that the disorder induced by milling either griseofulvin or folodipine consists of crystal defects rather than amorphous regions. The exothermic event in the milled samples is attributed to the crystallization of defects in the crystal. These results when combined with the IGC measurements indicate that the milled material retains its crystalline character, making it more stable (at the core) than the amorphous form. However, the milled material has also the most active surface, making itthe more interactive with other surfaces as an activated powder.
Sai Prasanth Chamarthy, Rodolfo Pinal, Colloids and Surfaces A: Physicochem. Eng. Aspects 331 (2008) 68–75

T0048 – Weak solid–solid transitions in pharmaceutical crystalline solids detected via thermally stimulated current

To demonstrate the ability of thermally stimulated current (TSC), normally used to study amorphous systems, in detecting weak solid–solid transitions in crystalline pharmaceutical compound. Methods: Polymorphs of a new chemical entity, LAU254, were generated and characterized using conventional and hot plate X-ray diffraction, DSC and TSC. Equilibration of 50:50 mixtures of the different polymorphs and solubility studies were conducted in aqueous and organic solvent at 25 and 50 ?C and then analyzed by X-ray and DSC. Results: Four crystalline forms (A–D) were isolated. formBshowed one single endotherm at 180 ?Cwhile the other forms showed lower melting endotherms, a crystallization exotherm and eventually a final melting endotherm corresponding to that of form B (180 ?C). The heat of fusion of form B was the highest. In contrast, solubility as well as mixture equilibration studies resulted in all forms converting to form A. TSC analysis revealed a well-defined reproducible peak with a maximum at ?130 ?C which was suspected to be a solid–solid transition. This was confirmed by hot plate X-ray diffraction where careful probing around 120–130 ?C revealed three different forms; form A (the initial form), a second form that appears above 150 ?C, melts, crystallizes and produces form B. Careful inspection of larger sample sizes in DSC showed a small endotherm at ?130 ?C. Conclusions: TSC, normally used to study amorphous systems, proved to be useful in detecting weak solid–solid transitions in crystalline pharmaceuticals, an application that has never been explored or reported previously. This resulted in identifying a form, obtainable only at temperatures above the transition temperature (related enantiotropically to the form that is most stable at ambient temperatures) and in reconciling the DSC and solubility data. TSC can be very useful in detecting and probing those transitions that occur in the solid state due to subtle dipolar motion and are not associated with large changes in global motion and heat capacity that is needed for detection by DSC and therefore can be complementary to DSC in obtaining a more complete assessment of the polymorphism behavior of crystalline solids.
Rama A. Shmeis, Steven L. Krill Thermochimica acta (2004) article in press

T0044 – A mechanistic investigation of an amorphous pharmaceutical and its solid dispersions. Part II: Molecular mobility and activation thermodynamic parameters

The ability of TSDC to characterize further amorphous materials beyond that possible with DSC was presented in part I (16) of this work. The purpose of part II presented here is to detect and quantitatively characterize time-scales of molecular motions (relaxation times) in amorphous solids at and below the glass transition temperature, to determine distributions of relaxation times associated with different modes of molecular mobility and their temperature dependence, and to determine experimentally the impact upon these parameters of combining the drug with excipients (i.e., solid dispersions at different drug to polymer ratios). The knowledge gleaned may be applied toward a more realistic correlation with physical stability of an amorphous drug within a formulation during storage. Methods. Preparation of amorphous drug and its solid dispersions with PVPK-30 was described in part I (16). Molecular mobility and dynamics of glass transition for these systems were studied using TSDC in the thermal windowing mode. Results. Relaxation maps and thermodynamic activation parameters show the effect of formulating the drug in a solid dispersion on converting the system (drug alone) from one with a wide distribution of motional processes extending over a wide temperature range at and below Tg to one that is homogeneous with very few modes of motion (20% dispersion) that becomes increasingly less homogeneous as the drug load increases (40% dispersion). This is confirmed by the high activation enthalpy (due to extensive intra- and intermolecular interactions) as well as high activation entropy (due to higher extent of freedom) for the drug alone vs. a close to an ideal system (lower enthalpy), with less extent of freedom (low entropy) especially for the 20% dispersion. The polymer PVPK-30 exhibited two distinct modes of motion, one with higher values of activation enthalpies and entropy corresponding to -relaxations, the other with lower values corresponding to -relaxations characterized by local noncooperative motional processes. Conclusions. Using thermal windowing, a distribution of temperature- dependent relaxation times encountered in real systems was obtained as opposed to a single average value routinely acquired by other techniques. Relevant kinetic parameters were obtained and used in mechanistically delineating the effects on molecular mobility of temperature and incorporating the drug in a polymer. This allows for appropriate choices to be made regarding drug loading, storage temperature, and type of polymer that would realistically correlate to physical stability.
R.A. Shmeis, Z. Wang and S.L. Krill, Pharmaceutical Research 21 (2004) 2031-2039

T0043 – A mechanistic investigation of an amorphous pharmaceutical and its solid dispersions. Part I: A comparative analysis by Thermally Stimulated Depolarization Current and Differential Scanning Calorimetry

To explore using thermally stimulated depolarization current (TSDC), in comparison to differential scanning calorimetry (DSC), for the characterization of molecular mobility of an amorphous pharmaceutical new chemical entity (LAB687), an amorphous polymer (PVPK-30), and their combination as solid dispersions at different % drug loadings. Methods. Amorphous drug was prepared by quenching from the melt. Solid dispersions containing 10-60% of drug in polymer were prepared by solvent evaporation method. Glass transition temperatures (Tg) were determined by DSC and TSDC. Results. In comparison to a single Tg obtained from DSC for the drug substance, TSDC shows two overlapping relaxations. Both peaks correspond to -relaxations that are associated with the glass transition, with the second peak corresponding to the rigid fraction that is difficult to be detected by DSC because it is associated with only small changes in heat capacity. Two overlapping relaxations were also observed for the polymer vs. one Tg by DSC. The lower temperature relaxation is believed to be a beta-relaxation, whereas the higher temperature transition corresponds to an alpha-relaxation. For the solid dispersions, one single peak was obtained for each of the 20% and 30% dispersions in excellent agreement with the DSC results. However, at the 40% drug load, a small shoulder was observed by TSDC at the low temperature of the main peak. This shoulder becomes more pronounced and overlaps with the main peak as the drug load increases to 50% and 60%. Agreement between the Tg values calculated by the Gordon-Taylor equation and the DSC and TSDC experimental data, especially for the 20% and 30% drug loading, indicate ideal miscibility. At higher drug loads, only by TSDC was it possible to detect the saturation level of the drug in the polymer. Conclusions. TSDC proved to be very sensitive in detecting small reorientational motions in solids and in separating overlapping events with only slight differences in molecular motion exhibited as broad events in DSC. This allowed for detection of the rigid fraction of the amorphous drug, the sub-glass transition beta-relaxation in the polymer, and the limit of miscibility between the drug and the polymer in the solid dispersions.
R.A. Shmeis, Z. Wang and S.L. Krill, Pharmaceutical Research 21 (2004) 2025-2030

T0041 – Detection of low levels of the amorphous phase in crystalline pharmaceutical materials by Thermally Stimulated Current Spectrometry

To demonstrate the applicability of thermally stimulated current (TSC) spectrometry for the detection of low levels of the amorphous phase in crystalline pharmaceutical materials. Methods. A crystalline drug substance was melt quenched to produce an amorphous material. Blends of the crystalline and amorphous phases in different ratios (from 75:25 to 99:01) were prepared by serial dilution. TSC studies were performed by applying an electric field at a temperature above the glass transition temperature (Tg) to orient the dipoles, rapidly cooling to 0°C, short circuiting for 1 min, and scanning at 7°C/min to measure the depolarization current. The temperature of the peak in the spectrum corresponds to the Tg of the amorphous phase. Modulated differential scanning calorimtery (DSC) studies were performed using three different test protocols (varying linear heating rate, modulation amplitude, and time period). Powder X-ray diffraction (XRD) studies were performed using a Siemens D500 diffractometer. Results. The ability to detect the amorphous phase by powder XRD is beset with problems due to indirect inference, orientation effects, and instrument-related intensity variations. Even using a consistent sampling procedure and an internal standard, the XRD could quantify the amorphous phase at a level of 5%. In the conventional or modulated DSC, the amorphous phase manifests itself as a shift in the baseline. Using modulated DSC it was possible to detect the amorphous phase at a level of 5% when tested at a heating rate of 2°C/min and an amplitude of ±1.0°C with a period of 30 s. The moisture sorption method appears to have a similar detection capability. In TSC scans, the glass transition event due to molecular/segmental mobility in the amorphous phase was manifested as a peak/shoulder on the low-temperature side of the depolarization peak of the crystalline phase. The amorphous phase was unambiguously detected at 2% with a lower detection limit of ~1%. Conclusions. On the basis of the results of this preliminary investigation, TSC appears to be capable of detecting the amorphous phase at as low as ~1% in crystalline pharmaceuticals, thus offering a much needed capability in discerning factors.
G.M. Venkatesh, M.E. Barnett, C. Owusu-Fordjour, and M. Galop, Pharmaceutical Research 18 (2001) 98-103

T0037 – Weak solid-solid transitions in pharmaceutical crystalline solids detected via thermally stimulated current

To demonstrate the ability of thermally stimulated current (TSC), normally used to study amorphous systems, in detecting weak solid-solid transitions in crystalline pharmaceutical compound. Methods: Polymorphs of a new chemical entity, LAU254, were generated and characterized using conventional and hot plate X-ray diffraction, DSC and TSC. Equilibration of 50:50 mixtures of the different polymorphs and solubility studies were conducted in aqueous and organic solvent at 25 and 50°C and then analyzed by X-ray and DSC. Results: Four crystalline forms (A-D) were isolated. Form B showed one single endotherm at 180°C while the other forms showed lower melting endotherms, a crystallization exotherm and eventually a final melting endotherm corresponding to that of form B (180°C). The heat of fusion of form B was the highest. In contrast, solubility as well as mixture equilibration studies resulted in all forms converting to form A. TSC analysis revealed a well-defined reproducible peak with a maximum at 130°C which was suspected to be a solid-solid transition. This was confirmed by hot plate X-ray diffraction where careful probing around 120-130°C revealed three different forms; form A (the initial form), a second form that appears above 150°C, melts, crystallizes and produces form B. Careful inspection of larger sample sizes in DSC showed a small endotherm at 130°C. Conclusions: TSC, normally used to study amorphous systems, proved to be useful in detecting weak solid-solid transitions in crystalline pharmaceuticals, an application that has never been explored or reported previously. This resulted in identifying a form, obtainable only at temperatures above the transition temperature (related enantiotropically to the form that is most stable at ambient temperatures) and in reconciling the DSC and solubility data. TSC can be very useful in detecting and probing those transitions that occur in the solid state due to subtle dipolar motion and are not associated with large changes in global motion and heat capacity that is needed for detection by DSC and therefore can be complementary to DSC in obtaining a more complete assessment of the polymorphism behavior of crystalline solids.
R.A. Shmeis and S.L. Krill, Thermochimica Acta 427(2005) 61-68

T0036 – The determination of the activation energy of a relaxational process from thermally stimulated depolarisation currents (TSDC) data: an illustration with the beta-relaxation of maltitol

Three different and independent procedures to obtain the activation energy of a motional process from thermally stimulated depolarisation currents (TSDC) data are reported. One of the procedures requires a single thermal sampling (TS) experiment: the activation energy is calculated from the temperature dependence of the relaxation time associated with this TS peak. The other two procedures are based on the influence of the heating rate on the features of the TS peak namely, on the temperature location Tm and on the intensity of the maximum I(Tm) of the peak. The illustration with the case of an elementary component of the beta-relaxation of maltitol shows that the values of the activation energy provided by these procedures are in good mutual agreement. The fact that the TSDC technique provides different and independent procedures to obtain the kinetic parameters of a motional process is a unique feature in the context of the experimental techniques most often used to study molecular mobility.
J.J. Moura Ramos and N.T. Correia, Thermochimica Acta 426 (2005) 185-190

T0012 – Dielectric study of the molecular mobility and the isothermal crystallization kinetics of an amorphous pharmaceutical drug substance

During the development of new pharmaceutical products based on drug substances in their amorphous form, the molecular mobility of an amorphous active ingredient was characterized in detail within a very broad time-temperature range. The relation between the isothermal crystallization kinetics and the dynamics of this amorphous substance was investigated. First, dynamic dielectric spectroscopy (DDS) and the thermostimulated current (TSC) techniques were used to analyze the molecular mobility of the amorphous drug substance over a wide frequency and temperature range (the drug substance is referred to as SSR in this text and was chosen as a model glassforming system). Two relaxation processes, corresponding to different molecular motions, were identified. The beta(a)-relaxation process, associated with intramolecular oscillation of small dipolar groups, followed Arrhenius temperature behavior over the entire time-temperature domain that was studied. However, the main alpha(a)-relaxation process, assigned to the dielectric manifestation of the dynamic glass transition of the amorphous phase, was described by Vogel-Fulcher-Tammann (VFT) and Arrhenius behavior above and below the glass transition temperature (Tg) respectively. The physical meaning of these complex dynamics is explained in the context of the Adam and Gibbs (AG) model, by the temperature dependence of the size of cooperatively rearranging regions (CRR) that govern the time scale of delocalized molecular motions. The distinction between the molecular mobility and the structural relaxation of amorphous systems below Tg is discussed. This work shows that the complementary nature of bothDDSandTSCtechniques is essential to directly analyze the intramolecular and molecular motions of disordered phases over a wide time-temperature range above and below the Tg. Second, real-time dielectric measurements were carried out to determine the isothermal crystallization kinetics of the SSR amorphous drug. Whatever the crystalline form obtained over time in the crystallization process, the decrease of the dielectric response of amorphous phase, which is characteristic of the isothermal crystallization, was studied to monitor the time dependence of the degree of crystallinity. The characteristic crystallization time, derived from Kohlrausch-Williams-Watt (KWW)- Avrami analyses performed at different temperatures, followed an Arrhenius temperature dependence. Behaviors specific to the molecular mobility of the amorphous drug substance were compared with the characteristic crystallization time. It was concluded that the crystal growth process of the SSR drug seems to be controlled by the intramolecular motions involving the beta(a)-relaxation mode and not by the molecular motions responsible for the alpha(a)-relaxation mode in the range of temperatures >Tg. Subsequent studies will focus on the crystallization process of the SSR drug in the glassy state (T
J. Alie, J. Menegotto, P. Cardon, H. Duplaa, A. Caron, C. Lacabanne, M. Bauer, Journal of Pharmaceutical Science 93 (2004) 218-233

T0002 – Thermal analysis of amorphous phase in a pharmaceutical drug

Thermally Stimulated Current (TSC) spectroscopy and Differential Scanning Calorimetry (DSC) have been applied to the characterization of the microstructure of a pharmaceutical drug. The dielectric relaxation spectrum shows two modes located in the temperature range of the glass transition. They have been attributed to the molecular mobility in the true amorphous phase and in the rigid amorphous region.
F. Fagegaltier, A. Lamure, C. Lacabanne, A. Caron, H. Mifsud and M. Bauer, Journal of Thermal Analysis and Calorimetry 48 (1997) 459-464

T0001 – Molecular mobility study of amorphous and crystalline phases of a pharmaceutical product by thermally stimulated current spectroscopy

Two crystalline forms and the amorphous state of irbesartan, a pharmaceutical drug chosen as a model, were analyzed by Thermally Stimulated Current (TSC) spectroscopy, a powerful technique currently used in polymer science to investigate the molecular dynamics of heterogeneous and complex materials. Whereas no specific dielectric response was noted for the B crystalline form, the A form of irbesartan exhibited molecular motions localized inside its channel structure. The dynamics involved in the dielectric glass transition of amorphous samples followed a compensation law characteristic of highly cooperative relaxation processes. Concerning the amorphous content in physical mixtures, a calibration curve and a limit of detection (2.5%) were established. The limit of detection could be improved by optimizing the TSC experimental parameters. The amorphous sample recrystallized at a single temperature was interpreted by the "idealized one-state model" defined here to describe systems composed of identical semicrystalline particles in which amorphous and crystalline phases are independent of each other (i.e., no chemical and physical interaction between the two phases). Therefore, the idealized one-state model may be simulated by a twostate model, which is representative of the two-phase model. Other samples recrystallized through a complex annealing stage were explained by the classical one-state model in agreement with the three-phase model used to describe bulk semicrystalline systems. These results demonstrate that, as for polymers, the semicrystalline state of pharmaceutical drugs should not be considered as a single state but as a more complex system that can be described as an idealized one-state model or a one-state model depending on the applied thermal treatment. These results give a new view that should be taken into account in the development of amorphous pharmaceutical drugs and formulations
N. Boutonnet-Fagegaltier, J. Menegotto, A. Lamure, H. Duplaa, A. Caron, C. Lacabanne, M. Bauer, Journal of Pharmaceutical Sciences 91(2002) 1548-1560

E0102 – Thermal study of complex formation of triamterene with B-cyclodextrin by spray-drying and co-grinding

The formation of crystalline inclusion complex of triamterene with beta-cyclodextrin (beta-CD) was studied, evaluating the thermal behaviour and dispersion state of this drug in different types of binary systems. Spray-drying and co-grinding (oscillating mill) mixtures of triamterene with beta-CD were prepared in 1:1 molar ratio. The changes of crystalline properties of original (untreated) triamterene, beta-CD, and composites obtained by co-grinding and spray-drying were investigated in comparison with those produced in simple physical mixtures. The thermal behaviour of the different samples was investigated using DTA. X-ray diffraction was applied as a complementary technique. The results have been explained by formation of amorphous drug particles on spray-drying samples and co-grinding or alternatively by means of a solid dispersion formation or a combination of these two. A contamination effect by grinding media was also observed as increasing grinding time.
J.M. Ginés, M.J. Arias, C. Novak, P.J. Sanchez-Soto, A. Ruiz-Conde, E. Morillo, Journal of Thermal Analysis and Calorimetry 45 (1995) 659-666

B3362 – Mitigation of diabetes-related complications in implanted collagen and elastin scaffolds using matrix-binding polyphenol

There is a major need for scaffold-based tissue engineered vascular grafts and heart valves with long-term patency and durability to be used in diabetic cardiovascular patients. We hypothesized that diabetes, by virtue of glycoxidation reactions, can directly crosslink implanted scaffolds, drastically altering their properties. In order to investigate the fate of tissue engineered scaffolds in diabetic conditions, we prepared valvular collagen scaffolds and arterial elastin scaffolds by decellularization and implanted them subdermally in diabetic rats. Both types of scaffolds exhibited significant levels of advanced glycation end products (AGEs), chemical crosslinking and stiffening -alterations which are not favorable for cardiovascular tissue engineering. Pre-implantation treatment of collagen and elastin scaffolds with penta-galloyl glucose (PGG), an antioxidant and matrix-binding polyphenol, chemically stabilized the scaffolds, reduced their enzymatic degradation, and protected them from diabetes-related complications by reduction of scaffold-bound AGE levels. PGG-treated scaffolds resisted diabetes-induced crosslinking and stiffening, were protected from calcification, and exhibited controlled remodeling in vivo, thereby supporting future use of diabetes-resistant scaffolds for cardiovascular tissue engineering in patients with diabetes.
James P. Chow, Dan T. Simionescu, Harleigh Warner, Bo Wang, Sourav S. Patnaik, Jun Liao, Agneta Simionescu, Biomaterials 34 (2013) 685-695

B3358 – On the correlation between hydrogen bonding and melting points in the inositols

Inositol, 1,2,3,4,5,6-hexahydroxycyclohexane, exists in nine stereoisomers with different crystal structures and melting points. In a previous paper on the relationship between the melting points of the inositols and the hydrogen-bonding patterns in their crystal structures [Simperler et al. (2006). CrystEngComm 8, 589], it was noted that although all inositol crystal structures known at that time contained 12 hydrogen bonds per molecule, their melting points span a large range of about 170 °C. Our preliminary investigations suggested that the highest melting point must be corrected for the effect of molecular symmetry, and that the three lowest melting points may need to be revised. This prompted a full investigation, with additional experiments on six of the nine inositols. Thirteen new phases were discovered; for all of these their crystal structures were examined. The crystal structures of eight ordered phases could be determined, of which seven were obtained from laboratory X-ray powder diffraction data. Five additional phases turned out to be rotator phases and only their unit cells could be determined. Two previously unknown melting points were measured, as well as most enthalpies of melting. Several previously reported melting points were shown to be solid-to-solid phase transitions or decomposition points. Our experiments have revealed a complex picture of phases, rotator phases and phase transitions, in which a simple correlation between melting points and hydrogen-bonding patterns is not feasible
Sandor L. Beko, Edith Alig, Martin U. Schmidt, Jacco van de Streek, IUCrJ (2014). 1, 61–73

B3357 – Ordered mesoporous silica and aluminosilicate-type matrix for amikacin delivery systems

Amikacin, which belong to aminoglycosides class of antibiotics, was used to obtain drug delivery systems based on MCM-41-type supports. In order to study the factors that influence the adsorption and in vitro release of amikacin, a series of mesostructured silica and aluminosilicates were employed as carriers. The toxicity of the supports was evaluated by proliferation tests on murine fibroblastic cells (3T3) and no significant toxic effect was observed. Small-angle and wide-angle X-ray diffraction data, N2 adsorption/desorption isotherms, as well as DSC analyses proved the presence of drug molecules in amorphous state into the channels of mesostructured MCM-41-type supports. It was found that the amikacin uptake depends mainly on the total pore volume of the carrier. The aluminum content in the mesostructured matrix with average pore size smaller than 2.4 nm is favorable to the drug uptake. In vitro release profiles in phosphate buffer solution, pH 7.4, exhibited a burst effect of 40% drug in the first hour of the assay, followed by a slow rate of amikacin delivery. Slower release kinetics and a lower amikacin cumulative release amount from mesostructured aluminosilicates than silica carriers were noticed.
Silviu Nastase, Laura Bajenaru, Cristian Matei, Raul Augustin Mitran, Daniela Berger, Microporous and Mesoporous Materials 182 (2013) 32–39

B3354 – Enhanced water-solubility of Licorice extract microparticle prepared by antisolvent precipitation process

In this study, Licorice extract (LE) microparticles were successfully prepared using antisolvent precipitation process. Ethyl acetate and dimethyl sulfoxide, were used as the antisolvent and solvent, respectively. By means of orthogonal experimental design, the influences of several process parameters on the mean particle size (MPS) were investigated. The concentration range of the LE solution, the volume ratio of solvent to antisolvent, dripping speed, and temperature were 4.3–34.5 mg/mL, 1:1–1:12, 1–10 mL/min, and 20–35 °C, respectively. Based on the above orthogonal experiments, the optimum antisolvent precipitation process conditions were found to be: temperature 20 °C, concentration of the LE solution 17.2 mg/mL, volume ratio of solvent to antisolvent 1:4, dripping speed 10 mL/min. The LE microparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform-infrared (FT-IR) spectroscopy, thermal gravimetric analysis (TG), differential scanning calorimetry (DSC), HPLC analysis and dissolution test. And the morphology, crystalline state and chemical structure, drug purity, dissolution rate and bioavailability of LE microparticles were investigated. Under optimum antisolvent precipitation process conditions, the MPS of LE microparticles reached to 85.3 nm, and with uniform distribution. And the LE microparticles had the same chemical structure as the unprocessed drug, but the crystallinity was reduced, purity was increased. Furthermore, the water solubility increased from 4.82 mg/mL to 16.10 mg/mL, and bioavailability is increased by 64.36%.
Chang Zu, Xiaowei Du, Xiuhua Zhao, Advanced Powder Technology (2013)

B3340 – Biophysical changes induced by xenon on phospholipid bilayers

Structural and dynamic changes in cell membrane properties induced by xenon, a volatile anesthetic molecule, may affect the function of membrane-mediated proteins, providing a hypothesis for the mechanism of general anesthetic action. Here, we use molecular dynamics simulation and differential scanning calorimetry to examine the biophysical and thermodynamic effects of xenon on model lipid membranes. Our results indicate that xenon atoms preferentially localize in the hydrophobic core of the lipid bilayer, inducing substantial increases in the area per lipid and bilayer thickness. Xenon depresses the membrane gel-liquid crystalline phase transition temperature, increasing membrane fluidity and lipid head group spacing, while inducing net local ordering effects in a small region of the lipid carbon tails and modulating the bilayer lateral pressure profile. Our results are consistent with a role for nonspecific, lipid bilayer-mediated mechanisms in producing xenon's general anesthetic action.
Ryan D. Booker, Amadeu K. Sum, Biochimica et Biophysica Acta 1828 (2013) 1347–1356

B3333 – Thermotropic and structural effects of poly(malic acid) on fully hydrated multilamellar DPPC–water systems

The thermotropic and structural effects of low molecular weight poly(malic acid) (PMLA) on fully hydrated multilamellar dipalmitoylphosphatidylcholine (DPPC)-water systems were investigated using differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), and freeze-fracture transmission electron microscopy (FFTEM). Systems of 20wt% DPPC concentration and 1 and 5wt% PMLA to lipid ratios were studied. The PMLA derivatives changed the thermal behavior of DPPC significantly and caused a drastic loss in correlation between lamellae in the three characteristic thermotropic states (i.e., in the gel, rippled gel and liquid crystalline phases). In the presence of PBS or NaCl, the perturbation was more moderate. The structural behavior on the atomic level was revealed by FTIR spectroscopy. The molecular interactions between DPPC and PMLA were simulated via modeling its measured infrared spectra, and their peculiar spectral features were interpreted. Through this interpretation, the poly(malic acid) is inferred to attach to the headgroups of the phospholipids through hydrogen bonds between the free hydroxil groups of PMLA and the phosphodiester groups of DPPC.
Szilvia Berényi, Judith Mihály, Sándor Kristyán, Lívia Naszályi Nagy, Judit Telegdi, Attila Bóta, Biochimica et Biophysica Acta 1828 (2013) 661–669

B3302 – The Binary Phase Diagram of Propranolol Hydrochloride and Crystallization-Based Enantioseparation

Inconsistent results were reported for the solid-state nature of the racemic species of the pharmaceutical relevant compound propranolol hydrochloride. In this work the binary phase diagram of the propranolol hydrochloride enantiomers is studied. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and high performance liquid chromatography (HPLC) were used as analytical methods. The type of the racemic species, the presence and extent of partial solid solutions and the stability regions of polymorphic forms in the system were investigated. The identified binary phase diagram is sketched. Finally, the feasibility of crystallization-based resolution is discussed.
Daniel Polenske, Heike Lorenz, Andreas Seidel-Morgenstern, Journal of Pharmaceutical Sciences, VOL. 99, NO. 4, April 2010

B3287 – An ester derivative of the drug gabapentin: pH dependent crystal stability

Gabapentin solutions with different pHs were prepared and slow crystallization was allowed to occur. Different crystalline forms were obtained at pHs up to 7, whereas alkaline media (pH 9) gave rise to an amorphous product. A new crystal structure of an ethyl ester derivative, obtained at pH 2 under Fischer esterification conditions, is described herein. Esterification blocked the supramolecular interactions typically observed through the carboxyl group of gabapentin, which resulted in a dramatic change in the solid-state structure. As it is known, this change could have a marked influence on the physiological absorption characteristics of the drug, which supports the search for ester-based gabapentin prodrugs as a means of improving the limited bioavailability of the drug.
Vânia André, M. Matilde Marques, M.F. Minas da Piedade, M. Teresa Duarte, Journal of Molecular Structure 973 (2010) 173–179

B3281 – Influence of polymer content on stabilizing milled amorphous salbutamol sulphate

The study investigates the influence of polyvinyl pyrrolidone (PVP) concentration on stabilizing the amorphous form of salbutamol sulphate (SS) before and after storage under ambient and elevated humidity conditions. Different mass ratios of SS and PVP (0-90wt%) were co-milled using a planetary ball mill. X-ray powder diffraction (XRPD), high sensitivity differential scanning calorimetry (HSDSC), dynamic vapor sorption (DVS), infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and Raman microscopy (RM) were used to analyze the stability of the co-milled mixtures against heat and humidity treatments as well as storage at different humidity conditions. Prior storage, DSC and DVS analyses revealed that re-crystallization of amorphous SS was suppressed above PVP content of 33 wt%. Probable hydrogen bond interaction between SS and PVP was found in FT-IR analysis. XRPD diffractograms and SEM analysis showed stability against re-crystallization was achieved in the co-milled mixtures with a minimum PVP content of 80 wt% after storage. Homogeneous distribution of SS and PVP from RM analysis showed fine clustering of SS and PVP, suggesting the formation of an amorphous dispersion at molecular level. The results provide insights on the application of thermal and humidity treatments, accelerated stability testing and investigations on drug-excipient interactions to predict the minimum ratio of an excipient for stabilizing the amorphous state of a milled API.
P.N. Balani, S.Y. Wong, W.K. Ng, E. Widjaja, R.B.H. Tan, S.Y. Chan, International Journal of Pharmaceutics 391 (2010) 125–136

B2657 – Influence of dilution on the thermophysical properties of Dax peloid (TERDAX®)

In thermotherapy, the efficiency of a peloid depends in particular on its thermal quality and an appropriate and detailed chemical and physical characterization is necessary to understand the thermal behaviour of these products. The most influential physical properties are the specific heat capacity, the thermal conductivity and the density. This work focuses on the study of the evolution of those properties of Dax peloid mixed with thermal and mineral water as a function of the mud concentration. The experimental specific heat capacity data were measured using a Calvet calorimeter, SETARAM BT 2.15, which permits studying with high precision all kind of substances and materials (oils, polymers, hydrates, powders) and simulate almost any process condition (reactions, crystallisation, freezing, etc.) and in the temperature range from 298.15 to 314.15 K. The pycnometer method and an Anton-Paar DMA-4500 vibrating-tube densimeter were used to measure density values while the thermal conductivity was determined by the Model KD2 Pro, Decagon Devices Inc. The experimental data show the expected behaviour: the specific heat capacity increases with temperature and decreases with concentration whereas density decreases with temperature and increases with concentration. Besides the thermal conductivity increases with both temperature and concentration. The results of this study will be used to determine the best proportion between peloid and mineral water for an individual mud bath.
A. Knorst-Fouran, L.M. Casás, J.L. Legidb, C. Coussina, D. Bessièrec, F. Plantier ,J. Lagièra, K. Duboura, Thermochimica Acta 539 (2012) 34– 38

B2544 – Use of isothermal microcalorimetry for prediction of oxidative stability of several amino acids

Isothermal microcalorimetry has been applied as a method for predicting (in)stability of ascorbic acid and several amino acids that undergo oxidative degradation in aqueous media. The fast and simple method involved the addition of different amounts of hydrogen peroxide. The appearance of the heat flow curves gave a clear general indication of how stability was influenced. The accuracy of the microcalorimetric result was investigated by comparing it with an HPLC assay and a good agreement between the results of both methods was demonstrated. It was also established that susceptibility to oxidative degradation decreases in the following order: cysteine, methionine, ascorbic acid, tyrosine and tryptophan
R. Roskar, M. Vivoda, V. Kmetec, Journal of Thermal Analysis and Calorimetry, Vol. 92 (2008) 3, 791–794

B2464 – The redox state influences the interaction of ubiquinones with phospholipid bilayers. A DSC study

Differential scanning calorimetry (DSC) has been used to study the interaction of ubiquinones (UQn) and their reduced forms, ubiquinols (UQnH2), with dipalmitoylphosphatidylcholine (DPPC) in multilamellar vesicles. The influence of the redox state has been investigated by comparing the effect of two ubiquinones with four (UQ4) and ten isoprene units (UQ10). In the presence of increasing amounts of UQ4 or UQ4H2, concomitant shift of the gel to liquid crystalline phase transition towards lower temperatures and vanishing of the pre-transition are observed. Short-chain homologues are thus inserted parallel to phospholipid chains, their quinone ring close to the polar headgroups of the DPPC, with a larger degree of penetration for the reduced form. In addition, broadening and skewing of the main transition peak claim for a lateral self-organization in highly concentrated regions of UQ4 and UQ4H2, with a redox state influence on the distribution in size and shape of lipid domains. The lipid thermotropic behavior is not affected by the presence of UQ10 which remain homogeneously dispersed within the midplane of the phospholipid bilayer, while effect of reduced UQ10H2 argues for a different organization.
Y. Roche, P. Peretti, Sophie Bernard, Journal of Thermal Analysis and Calorimetry, Vol. 89 (2007) 3, 867–873

B2449 – Role of structural and macrocrystalline factors in the desolvation behaviour of cortisone acetate solvates

A combined analysis of structural data and experimental results (DSC, temperature-resolved XRPD and hot stage optical microscopy) revealed that the dehydration mechanism of cortisone acetate monohydrate (CTA·H2O) involves a collective and anisotropic departure of water molecules followed by a cooperative structural reorganization toward the anhydrous polymorph CTA (form 2). In spite of the lack of crystal structure data, it can be postulated from experimental data that thermal decomposition of the dihydrated form (CTA·2H2O) and of the tetrahydrofuran solvate (CTA·THF) toward another polymorph (CTA (form 3)) also proceeds according to a cooperative mechanism, thus giving rise to probable structural filiations between these crystalline forms of CTA. The crystal structure determination of two original solvates (CTA·DMF and CTA·DMSO) indicates that these phases are isomorphous to the previously reported acetone solvate. However, their desolvation behaviour does not involve a cooperative mechanism, as could be expected from structural data only. Instead, the decomposition mechanism of CTA·DMF and CTA·DMSO starts with the formation of a solvent-proof superficial layer, followed by the partial dissolution of the enclosed inner part of crystals. Hot stage optical microscopy observations and DSC measurements showed that dissolved materials (resulting from a peritectic decomposition) is suddenly evacuated through macroscopic cracks about 30°C above the ebullition point of each solvent. From this unusual behaviour, the necessity to investigate rigorously the various aspects (thermodynamics, kinetics, crystal structures and physical factors) of solvate decompositions is highlighted, including factors related to the particular preparation route of each sample.
S. Petit, F. Mallet, M.-N. Petit, G. Coquerel, Journal of Thermal Analysis and Calorimetry, Vol. 90 (2007) 1, 39–47

B2445 – Thermal stability evaluation of doping compounds before GC-MS analysis by DSC

The Medical Commission of the International Olympic Committee forbids the use of anabolic androgenic steroids, b-agonists, stimulant and narcotic compounds to improve athletic performance. In this work, we evaluated the thermal stability of 17 compounds by the use of the DSC for their potential GC-MS analysis either under free form or under TMS derivative form. In DSC, esterified and unesterified anabolic steroids were characterized by a true melting peak, followed by a large exothermic peak at about 251–316°C due to oxidative degradation. They could be analysed by GC-MS mainly under TMS derivatives. Hydroxylated and unhydroxylated stimulant compounds (xanthines) seemed to be more stable at high temperature. As unhydroxylated xanthines were not silylated with BSTFA – TMCS, their GC analysis would be done under their free forms. TMS derivatisation of albuterol hemisulfate and codeine phosphate is preferable. In our conditions, to analyse by GC-MS all 17 doping compounds in the same GC-MS run, the optimal silylation temperature and best column initial temperature were determined at both 60°C.
Y. Hadef, J. Kaloustian, A. Nicolay, H. Portugal, Journal of Thermal Analysis and Calorimetry, Vol. 93 (2008) 2, 553–560

B2417 – Solubility diagrams in solvent–antisolvent systems by titration calorimetry. Application to some pharmaceutical compounds in water–ethanol mixtures

Isothermal titration calorimetry (ITC) has been used to develop a method to construct the solid-liquid equilibrium line in ternary systems containing the solute to precipitate and an aqueous mixed solvent. The method consists in measuring the heat of dissolution of a solid component (the solute) during successive additions of the liquid solvent. The cumulated heat, resulting from the successive heat peaks obtained for the different injections of known volumes of solvent, plotted vs. the ratio of the numbers of moles nsolvent/nsolute is represented by two nearly straight lines. The intercept of the two lines gives the solubility limit and the corresponding enthalpy of dissolution of the solute in the solvent. Solubility diagrams have been established at 303.15 K in binary mixed solvents ethanol–water over the whole concentration range for seven compounds of pharmaceutical interest, namely: urea, phenylurea, l-valine, dl-valine, l-valine ethyl ester hydrochloride, tris(hydroxymethyl)amino methane.
M. H. Hamedi, J.-P. E. Grolier, Journal of Thermal Analysis and Calorimetry, Vol. 89 (2007) 1, 87–92

B2389 – The use of microcalorimetry and HPLC for the determination of degradation kinetics and thermodynamic parameters of perindopril erbumine in aqueous solutions

Perindopril Erbumine (PER) is one of the newly used angiotensin-converting enzyme inhibitors (ACE inhibitors) and is used for the treatment of patients with hypertension and symptomatic heart failure. It has two main degradation pathways, i.e. the degradation by hydrolysis and the degradation by cyclization. An isothermal heat conduction microcalorimetry (MC) and high pressure liquid chromatography (HPLC) were used for the characterization of aqueous solutions of PER and its stability properties. The rates of heat evolved during degradation of perindopril were measured by MC as a function of temperature and pH and from these data rate constant and change in enthalpy of the reactions were determined. With the HPLC method the concentration of perindopril and its degradation products were measured as a function of time in aqueous solutions of different pH that were stored at different temperatures. We demonstrated that reactions of degradation of perindopril at observed conditions follow the first order kinetics. The Arrhenius equation for each pH was determined. At pH 6.8 only one degradation pathway is present, i.e. the degradation by hydrolysis. Degradation constants for this pathway calculated from MC data are in good agreement with those obtained from HPLC. MC as a non-specific technique was shown to be useful in studies of PER when one reaction was present in the sample and also when more chemical and physical processes were simultaneously running
Z. Simoncic, R. Roskar, A. Gartner, K. Kogej, V. Kmetec, International Journal of Pharmaceutics (2007)

B2388 – Use of microcalorimetry in determination of stability of enalapril maleate and enalapril maleate tablet formulations

The stability properties of enalapril maleate (EM) and of different tablet formulations includingEMwere studied by isothermal microcalorimetry and by high performance liquid chromatography (HPLC). It was shown that water content of the sample and elevated temperature have a high impact on stability properties of the substance itself and of the formulations including this substance. The degradation is more extensive at higher water content and at elevated temperature. The type of the tablet formulation (5 or 20 mg EM tablet formulation) also has an impact: the 5 EM tablet formulation is the less stable one. The heat output of individual tablet formulations was used to evaluate the enthalpy changes and to calculate the difference in the amount of degraded EM between various samples. These results agreed satisfactorily with those obtained by HPLC. Isothermal microcalorimetry proved to be a fast and predictive method that could be used in preformulation studies to accelerate the pharmaceutical development and shorten the time before launching the product to the market.
Z. Simoncic, P. Zupancic, R. Roskar, A. Gartner, K. Kogej, V. Kmetec, International Journal of Pharmaceutics 342 (2007) 145–151

B2271 – Membrane effects of the antitumor drugs doxorubicin and thaliblastine: comparison to multidrug resistance modulators verapamil and trans-flupentixol

The interactions of the antitumor drugs doxorubicin and thaliblastine with model membranes composed of neutral (phosphatidylcholine) and negatively charged (phosphatidylserine) phospholipids were studied by differential scanning calorimetry and nuclear magnetic resonance. The membrane activities of doxorubicin and thaliblastine were compared to those of the powerful multidrug resistance (MDR) modulators trans-flupentixol and verapamil. The results point out to the potential role of the drug-membrane interactions for the effects of doxorubicin and thaliblastine in resistant tumor cells. They direct also to the artificial membranes as a suitable tool for screening of compounds with potential ability to modulate MDR.
I. Pajeva, D.K. Todorov, J. Seydel, European Journal of Pharmaceutical Sciences 21 (2004) 243-250

B2262 – Colloidal microgels as transdermal delivery systems

This paper presents a report of the synthesis of temperature-sensitive microgels based on a copolymer of butyl acrylate (10%) co-polyNIPAM (90%), in the presence of and in the absence of ibuprofen (IBU), methyl paraben (MP) and propyl paraben (PP), by a surfactant-free emulsion polymerisation in water. N',N'-methylenebisacrylamide was used as a cross-linking agent and potassium persulphate as an initiator. Physicochemical properties of the microgels were determined using different techniques including dynamic light scattering and transmission electron microscopy. It is speculated that the microgel appearance is similar to a core-shell microgel, having in the core the complex IBU or MP or PP-butyl acrylate and in the shell poly(NIPAM). Permeation across a model silicone membrane and human skin was investigated over a range of temperatures (292-313 K). The transport rate of IBU and, PP from these poly(NIPAM) microgels is significantly reduced by two and one orders of magnitude, respectively, compared with the transport rate from saturated solutions. Such a reduction in flux was not however observed for MP.
V. Castro Lopez, S.L. Raghavan, M.J. Snowden, Reactive & Functional Polymers 58 (2004) 175-185

B2254 – Microcomposites theophylline/hydrogenated palm oil from a PGSS process for controlled drug delivery systems

New controlled-release carriers of theophylline prepared with hydrogenated palm oil (HPO) were obtained by Particles from gas saturated solutions (PGSS) at different working pressures. Pressure had no significant effect on the mean diameter of the particles (of about 3.0 µm). However, spherical morphology with a regular surfacewas preferentially obtained at higher expansion pressures. HPLC analysis revealed a low theophylline encapsulation in the HPO matrix and showed that considerable amounts of theophylline were located at the particles' surface. Dissolution studies showed that theophylline released from the HPO matrix follows Higuchi's model for simple diffusional processes. However, successful correlation with experiment was achieved only with the Brophy and Deasy long-time correction to the Higuchi equation.
M. Rodrigues, N. Peiriço, H. Matos, E. Gomes de Azevedo, M.R. Lobato, A.J. Almeida, J. of Supercritical Fluids 29 (2004) 175-184

B2205 – Analysis of a mixture containing ampicillin anhydrate and ampicillin trihydrate by thermogravimetry, oven heating, differential scanning calorimetry, and X-ray diffraction techniques

Because the solubility of ampicillin anhydrate is quite different from that of ampicillin trihydrate, four basic techniques were employed to rapidly and precisely quantify mixtures of ampicillin anhydrate and ampicillin trihydrate. Using thermogravimetry and oven heating in a porcelain crucible, their ratio in mixtures was precisely quantified according to weight loss of water from ampicillin trihydrate in the mixtures. The ratio was also quantified based on the enthalpy change of water in ampicillin trihydrate and the phase change of ampicillin itself as measured by a differential scanning calorimeter. The X-ray diffraction intensity ratio of the mixtures at two specific angles was shown to be proportional to the ratio of the mixtures. Accordingly, a linear relationship between a change of physicochemical properties and a selected ratio of the mixtures was established. Comparison of the sample used, the R2 value from linear curve-fitting, the maximum error and maximum measure limit in different techniques is also presented.
C-L. Liu, S-M. Wu, T-C. Chang, M-L. Liu, H-J. Chiang, Analytica Chimica Acta 517 (2004) 237-243

B2170 – Transdermal self-permeation enhancement of ibuprofen

The objective of this study was to prepare saturated solutions of ibuprofen, of different concentrations, and to investigate their effect on permeation of ibuprofen across rat epidermis. Ibuprofen saturated solutions were prepared using 0.1, 0.2, 0.3 and 0.4 M disodium hydrogen phosphate solution (DHP). The solubility of ibuprofen in DHP increased as the molarity of DHP increased. Thus the four saturated solutions of ibuprofen (0.1M-DHP-IBU, 0.2M-DHP-IBU, 0.3M-DHP-IBU and 0.4M-DHPIBU) have different concentrations of the same drug, and showed same pH (pH 7.0 ± 1). The permeability study was also carried out using human epidermis and silastic membrane. Permeation rate of ibuprofen across rat epidermis and human epidermis from 0.4M-DHP-IBU was much greater than from 0.1M-DHP-IBU. The magnitudes of increase in the drug flux were 46.4-fold with rat epidermis and 9.4-fold with human epidermis. Such a great increase in drug flux was not observed with silastic membrane, only 1.4-fold. This suggests that the increased drug flux is likely due to drug-skin interaction and not the increased concentration of ibuprofen per se. Surface tension (ST) measurements of DHP versus ibuprofen concentration showed ST reduction of DHP, from 72 to 27.9 dyn/cm. This is an indication that ibuprofen acted as ionic surfactant and the observed skin permeability enhancement is attributed to disruption of stratum corneum barrier. Results of DSC study supported this assumption. DSC of untreated rat stratum corneum samples showed lipid transitions at 41.9 ± 0.0°C (T1), 55.1 ± 1.6°C (Tx), 70.2 ± 0.1°C (T2) and 77.5 ± 0.1°C (T3), while those pretreated with 0.4M-DHP-IBU did not show the first three lipid transitions. Also, pretreatment of rat epidermis with 0.4M-DHP-IBU enhanced permeation of diclofenac sodium greater than 1250-fold. This corroborates that ibuprofen not only enhances its own permeation but also that of other drugs, such as diclofenac sodium.
S.M. Al-Saidan, Journal of Controlled Release 100 (2004) 199-209

B2135 – Rapid assessment of the structural relaxation behavior of amorphous pharmaceutical solids: Effect of residual water on molecular mobility

Purpose. Use RH-perfusion microcalorimetry and other analytical techniques to measure the interactions between water vapor and amorphous pharmaceutical solids; use these measurements and a mathematical model to provide a mechanistic understanding of observed calorimetric events. Materials. Isothermal microcalorimetry was used to characterize interactions of water vapor with a model amorphous system, spray-dried raffinose. Differential scanning calorimetry was used to measure glass transition temperature, Tg. High-sensitivity differential scanning calorimetry was used to measure enthalpy relaxation. X-ray powder diffraction (XRPD) was used to confirm that the spray-dried samples were amorphous. Scanning electron microscopy (SEM) was used to examine particle morphology. Gravimetric vapor sorption was used to measure moisture sorption isotherms. Thermogravimetric analysis (TGA) was used to measure loss on drying. Results. A moisture-induced thermal activity trace (MITAT) provides a rapid measure of the dependence of molecular mobility on moisture content at a given storage temperature. At some relative humidity threshold, RHm, the MITAT exhibits a dramatic increase in the calorimetric rate of heat flux. Simulations using calorimetric data indicate that this thermal event is a consequence of enthalpy relaxation. Conclusions. RH-perfusion microcalorimetry is a useful tool to determine the onset of moisture-induced physical instability of glassy pharmaceuticals and could find a broad application to determine appropriate storage conditions to ensure long-term physical stability. Remarkably, thermal events measured on practical laboratory timescales (hours to days) are relevant to the stability of amorphous materials on much longer, pharmaceutically relevant timescales (years). The mechanistic understanding of these observations in terms of enthalpy relaxation has added further value to the use of RH-perfusion calorimetry as a rapid means to characterize the molecular mobility of amorphous solids.
D.P. Miller and D. Lechuga-Ballesteros, Pharmaceutical Research 23 (2006) 2291-2305

B2120 – Adiabatic calorimetry and thermal analysis on acetaminophen

Molar heat capacities of acetaminophen were precisely measured with a small sample precision automated adiabatic calorimeter over the temperature range from 80 to 330 K. A solid-solid transition at 149.96 K was found from the Cp,m-T curve. The polynomial functions of Cp,m(J K-1 mol-1) vs. T were established on the heat capacity measurements by means of the least square fitting method. Thermal decomposition processes of acetaminophen have been studied by thermogravimetry. And the thermal decomposition kinetics parameters, such as activation energy E, pre-exponential factor A and reaction order n, were calculated by TG-DTG techniques with the Freeman-Carroll method, Kissinger method and Ozawa method. Accordingly the thermal decomposition kinetics equation of acetaminophen is expressed as: dalpha/dt=2.67 x 10^7 x exp(-89630/RT) x (1-alpha)^0.23. The process of fusion has been investigated through DSC. The melting point, molar enthalpy and entropy of fusion are to be (441.89 ± 0.04) K, 26.49 ± 0.44 kJ mol-1 and 59.80 ± 1.01 J K-1 mol-1, respectively.
F. Xu, L. X. Sun, Z. C. Tan, J. G. Liang and T. Zhang, Journal of Thermal Analysis and Calorimetry 83 (2006) 187-191

B2108 – Solid state characterization of chloramphenicol palmitate. Raman spectroscopy applied to pharmaceutical polymorphs

A pharmaceutical active compound, chloramphenicol palmitate, appears in three polymorphic forms, that can be observed at room temperature. The stable form A (biologically inactive modification), the meta-stable form B (active modification) and unstable form C were found to have distinct Raman spectra, with bands attributable to the different polymorphs. The use of hot-stage Raman microscopy (the direct coupling of Raman microscopy and hot-stage) is demonstrated for the drug substance chloramphenicol palmitate form C. All modifications of form C were produced and identified by hot-stage Raman microscopy. A close correlation of thermal and spectroscopic information was achieved by this combination of techniques. As reported in several pharmacopoeias, the content of form A should be less than 10%; therefore, a mixture of 10% (w/w) A in B was prepared, and the presence of the characteristic bands of form A after subtraction of the pure B was revealed. Moreover, mixtures between 2 and 12% (w/w) A in B were investigated and the intensity ratio (as peak area) I(413-435) / I(1035-1158) as a function of A percentage has been demonstrated to show a linear trend. Other methods for the characterization of polymorphs were used: Fourier transform infrared spectroscopy (FT-IR), Diffuse reflectance infrared Fourier transform spectroscopy (DRIFT), Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD).
M.C. Gamberini, C. Baraldi, A. Tinti, C. Rustichelli, V. Ferioli, G. Gamberini, Journal of Molecular Structure 785 (2006) 216-224

B2087 – Safety Concerns Regarding the Transportation of Organic Powders on Dry Ice: How CO2 Adsorption Can Lead to Powder Spills

In the development of a new drug, samples of the active pharmaceutical ingredient (API) and of some intermediates needed to be shipped between laboratories in different countries. Since the stability of the API is limited at room temperature, these shipments were performed on dry ice. The product is not only thermally instable but also prone to hydrolysis and should therefore be kept away from humidity as much as possible. For this reason, it is standard procedure to open the sample bottles only when they are at room temperature, in order to prevent condensation of atmospheric moisture on the cold bottle or product. On several occasions, it was noted that pressure build-up occurred in the bottles when they had reached room temperature. In at least one case, the pressure build-up was so high that the lid was blown off the sample bottle, leading to a serious powder spill. Fortunately enough nobody was near the bottle at that time, so nobody was exposed to the powder. Obviously, the root causes of this pressure build-up needed to be known, so a detailed study was started.
Wim Dermaut, Jan van Dun, Jan De Kock,Ivan Vervest, and Christine Fannes Organic Process Research & Development 2008, 12, 130-131

B2048 – Experimental and computational study on the thermochemistry of ethylpiperidines

The standard (p° = 0.1 MPa) massic energies of combustion in oxygen of 1-ethylpiperidine and 2-ethylpiperidine, both in the liquid phase, were measured at T = 298.15 K by static bomb calorimetry. These values were used to derive the standard molar enthalpies of combustion and the standard molar enthalpies of formation, in the condensed phase, for these compounds. Further, the standard molar enthalpies of vaporization, at T = 298.15 K, of these two ethylpiperidine isomers were determined by Calvet microcalorimetry. The combustion calorimetry results together with those from the Calvet microcalorimetry, were used to derive the standard molar enthalpies of formation, at T = 298.15 K, in the gaseous phase. In parallel, theoretical calculations have been carried out for all the ethylpiperidine isomers, enabling the estimation of gas-phase enthalpies of formation for these compounds. The comparison with the present experimental data is very good and, thus, supports the quality of the results calculated for the 3-ethyl and 4-ethylpiperidines.
M.A.V. Ribeiro da Silva, J.I.T.A. Cabral, J.R.B. Gomes, J. Chem. Thermodynamics 38 (2006) 1072-1078

B2015 – Cefdinir: A comparative study of anhydrous vs. monohydrate form Microstructure and tabletting behaviour

Anhydrous cefdinir (AC) vs. monohydrated cefdinir (MHC) was compared in order to be used as antimicrobial in therapeutics. Different techniques have been used to characterize physically AC and MHC, and also a complete microstructural analysis of raw materials was carried out. Cefdinir and Maltodextrin QDM® 500 (3:2) formulations were compressed in order to obtain tablets with typical dose of Cefdinir, i.e. 300 mg. Dissolution profiles were obtained for both AC and MHC tablets. Finally tablet X-ray diffraction was performed to ensure the stability of the monohydrated form after tabletting being clearly different in both AC and MHC crystals. AC crystal structure was agreed with the known pattern of anhydrous Cefdinir described in the literature. Microstructural analysis showed large differences in specific surface area (SSA), confirmed by mercury intrusion. Crystal structures of both AC and MHC were stable under mixing, compression and storing processes. Dissolution profiles were faster for hydrate form, probably related to microstructural properties of the crystal which remained after tabletting. In conclusion, it is possible to isolate Cefdinir in two forms anhydrous and monohydrate, well characterized and differentiated. The use of this later improves dissolution of tablet dosage form due to the lack of interconversion during tablet manufacture.
W. Cabri, P. Ghetti, M. Alpegiani, G. Pozzi, A. Justo-Erbez, J.I. Pérez-Martinez, R. Villalon-Rubio, M.C. Monedero-Perales, A. Munoz-Ruiz, European Journal of Pharmaceutics and Biopharmaceutics 64 (2006) 212-221

B1975 – Crystal structure, thermal analysis and IR spectrometric investigation of L-tyrosine hydrazide diphosphate monohydrate

The monoclinic crystal structure of (C9H15N3O2)2P2O7.H2O denoted DLTHDP [a = 14.626(1), b = 6.1990(2), c = 14.562(1) Å, beta = 97.289(3)°, Z = 2, monoclinic P21, Dcal = 1.508, Dmes = 1.49 g cm-3] has been solved using direct methods and refined to a reliability factor R = 4.37% for 2079 independent reflections. The DLTHDP structure can be described by infinite polyanions [P2O7 H2O]n 4n- organized in chains parallel to the b-direction and located at z = 1/2, alternating with organic cations associated in ribbons spreading along the a-direction. Multiple hydrogen bonds originating from amine, hydroxyl groups and water molecules donors [N-H....O(N) and O(W)-H....O] connect the different components of the lattice. The IR data of DLTHDP is reported and discussed according to the theoretical group analysis and by comparison with IR results of similar compounds. The coupled thermogravimetric analysis (TGA)-differential thermal analysis (DTA) thermal study shows the departure of one water molecule, confirming the hydrated character of this compound.
A. Gharbi, T. Guerfel, A. Jouini, Materials Research Bulletin 41 (2006) 2024-2034

B1970 – Novel O-palmitoylscleroglucan-coated liposomes as drug carriers: Development, characterization and interaction with leuprolide

Polysaccharide-coated liposomes have been studied for their potential use for peptide drug delivery by the oral route because they are able to minimize the disruptive influences on peptide drugs of gastrointestinal fluids. The aim of this work was to synthesize and characterize a modified polysaccharide, O-palmitoylscleroglucan (PSCG), and to coate unilamellar liposomes for oral delivery of peptide drugs. To better evaluate the coating efficiency of PSCG, also scleroglucan (SCG)-coated liposomes were prepared. We studied the surface modification of liposomes and the SCG- and PSCG-coated liposomes were characterized in terms of size, shape, ? potential, influence of polymer coating on bilayer fluidity, stability in serum, in simulated gastric and intestinal fluids and against sodium cholate and pancreatin. Leuprolide, a synthetic superpotent agonist of luteinizing hormone releasing hormone (LHRH) receptor, was chosen as a model peptide drug. After polymer coating the vesicle dimensions increased and the ? potential shifted to less negative values. These results indicate that both SCGand PSCG-coated liposomes surface and DSC results showed that PSCG was anchored on the liposomal surface. The stability of coated-liposomes in SGF, sodium cholate solution and pancreatin solution was increased. From this preliminary in vitro studies, it seems that PSCG-coated liposomes could be considered as a potential carrier for oral administration.
M. Carafa, C. Marianecci, V. Annibaldi, A. Di Stefano, P. Sozio, E. Santucci, International Journal of Pharmaceutics 325 (2006) 155-162

B1969 – Solid lipid nanoparticles incorporated in dextran hydrogels: A new drug delivery system for oral formulations

Solid lipid nanoparticles (SLN) containing or not (S)-(+)-2-(4-isobutylphenyl)propionic acid (ibuprofen) were prepared with Preciol ATO 5 as lipid phase by the hot homogenization technique and characterized through particle size analyses and zeta potential measurements.DSCexperiments carried out on the freeze-dried samples of loaded SLN showed a shift of the melting endotherm of the lipid phase, with the maximum at a temperature value higher then that of the "empty" SLN. 1H NMR of the nanosuspension allowed to calculate the encapsulation efficiency of the particles that was 52±3%. By adding dextran methacrylate (DEX-MA) to the aqueous phase and submitting the mixture to UV irradiation, systems of SLN (drug-loaded and unloaded) incorporated into a dextran hydrogel were prepared. Finally, dissolution studies of ibuprofen from the freeze-dried samples were performed. The comparison among the release profiles of ibuprofen from SLN, DEX-MA hydrogel and SLN/DEX-MA-hydrogel allows to affirm that this last system, retaining about 60% of the drug after 2 h in acid medium and releasing it slowly in neutral solution, is suitable for modified delivery oral formulations.
M.A. Casadei, F. Cerreto, S. Cesa, M. Giannuzzo, M. Feeney, C. Marianecci, P. Paolicelli, International Journal of Pharmaceutics 325 (2006) 140-146

B1953 – Heat capacity and standard molar enthalpy of formation of crystalline 2,6-dicarboxypyridine (C7H5NO4)

Low-temperature heat capacity Cp,m of 2,6-dicarboxypyridine (C7H5NO4; CAS 499-83-2) was precisely measured in the temperature range from (80 to 378) K with a high precision automated adiabatic calorimeter. No phase transition or thermal anomaly was observed in this range. The thermodynamic functions [HT - H298.15] and [ST - S298.15] were calculated in the range from (80 to 378) K. The standard molar enthalpy of combustion and the standard molar enthalpy of formation of the compound have been determined, ?cHm°(C7H5NO4, cr) = - (2741.41 ± 0.49) kJ.mol-1 and ?fHm°(C7H5NO4, cr) = - (727.74 ± 1.50) kJ.mol-1, by means of a precision oxygen-bomb combustion calorimeter at T = 298.15 K. The thermodynamic properties of the compound were further investigated through differential scanning calorimeter (DSC) and the thermogravimetric (TG) analysis.
Q. Shi, Z-C. Tan, Y-Y. Di, X-C. Lv, B. Tong, Z-H. Zhang, L-X. Sun, T. Zhang, J. Chem. Thermodynamics 38 (2006) 1701-1705

B1952 – Thermodynamic studies on the interactions of diglycine with magnesium chloride in aqueous medium at different temperatures

Apparent molar heat capacities (CP2,?), apparent molar volumes (V2,?), and viscosities (?) of diglycine in water and in aqueous magnesium chloride (MgCl2) solutions of molality mS ? (0.05 to 0.70) mol.kg-1 over the temperature range T = (288.15 to 328.15) K have been determined using high sensitivity micro-differential scanning calorimeter, vibrating-tube digital density meter, and automatic viscosity measuring unit (AVS 350), respectively. The data have been used to calculate the partial molar heat capacities (CP2?) and partial molar volumes (V2?) at infinite dilution. The viscosity B-coefficients have also been obtained from viscosity data using Jones-Dole equation. The CP2? and V2? values of diglycine in aqueous MgCl2 solutions are higher than those in water and thus exhibit positive transfer functions (?trCP2? and ?trV2?), which are indicative of strong interactions between diglycine and MgCl2. Corresponding viscosity B-coef- ficients of transfer are also generally positive. The transfer functions decrease with increase in temperature and increase with the concentration of MgCl2. The free energies, enthalpies and entropies of activation for viscous flow of diglycine in aqueous MgCl2 solutions have been obtained by using the Feakins transition-state theory. Partial molar expansibilities (?V2?/?T) and (?²V2?/?T²)P at infinite dilution along with their temperature dependence, the interaction coefficients from the volume, heat capacity, and viscosity B-coefficients have been used to divulge the various kinds of plausible interactions between solute (diglycine) and cosolute (MgCl2) in solutions.
B.S. Lark, P. Patyar, T.S. Banipal, J. Chem. Thermodynamics 38 (2006) 1592-1605

B1935 – Interaction of isopropylthioxanthone with phospholipid liposomes

Isopropylthioxanthone (ITX) is a highly lipophilic molecule which can be released in foods and beverages from the packages, where it is present as photoinitiator of inks in printing processes. Recently it was found in babies milk, and its toxicity cannot be excluded. The structure of the molecule suggests a possible strong interaction with the lipid moiety of biological membranes, and this is the first study of its effects on phospholipid organization, using differential scanning calorimetry (DSC) and spin labelling techniques. The data obtained with multilamellar liposomes of saturated phospholipids of different length, with and without cholesterol, point out that the molecule changes the lipid structure; in particular, in the gel state, behaving like a disordering agent it increases the mobility of the bilayer, while, in the fluid state, tends to rigidify the membrane, in a cholesterol like way. This behavior supports the hypothesis that ITX experiences a relocation process when the lipid matrix passes from the gel to the fluid state.
F. Momo, S. Fabris, R. Stevanato, Biophysical Chemistry 127 (2007) 36-40

B1931 – Vapor-liquid equilibria and volume expansion of the tetrahydrofuran/CO2 system: Application to a SAS-atomization process

Using the synthetic method, vapor-liquid equilibria near the critical points of tetrahydrofuran (THF)/carbon dioxide mixtures were determined at 313 K, 323K and 333K and at pressures from 6MPa to 10MPa. The volume expansion of THF in high-pressure CO2 was measured in a high-pressure view cell at 308 K, 313K and 318K and at pressures from 1MPa to 8MPa. The correlation of the experimental VLE data with the Peng-Robinson equation of state and the Panagiotopoulos-Reid (P&R) mixing rules described better the experimental data than the same equation of state with the van der Waals one-fluid mixing rules. On the contrary, prediction of volume expansion data with van der Waals mixing rules agreed better with experimental data at low pressures than those predicted with the P&R mixing rules. The hydrogenated palm oil (HPO)/THF/CO2 system was studied to produce particles of HPO using a supercritical antisolvent (SAS) atomization process. Results indicate that the morphology of the produced HPO particles ranged from spheres to fibers. A discussion is presented on the effects of the initial state of the CO2/THF mixture on the particle morphology based on the phase equilibrium behavior around the critical points of the binary THF/CO2 mixtures, the atomization, and a differential scanning calorimetry (DSC) investigation. This discussion suggests that the initial state of the feed mixture determines the morphology of the produced particles-a two-phase vapor-liquid mixture favors the production of spheres due to atomization, whereas a mixture in a SCF state favors the formation of fibers due to crystallization.
J. Li, M. Rodrigues, A. Paiva, H.A. Matos, E. Gomes de Azevedo, J. of Supercritical Fluids 41 (2007) 343-351

B1930 – Determination of kinetic parameters from isothermal calorimetry for interaction processes of pyrimethamine with chitosan derivatives

The interaction of the antifolate drug pyrimethamine with chitosan derivatives, namely, chit-GLT (glutaraldehyde cross-linked chitosan gel beads) and chit-Cu (chit-GLT beads treated with copper solution) has been investigated from isothermal calorimetry at 298 and 308 K, being studied in terms of the Avrami and pseudo-first- and second-order kinetic models. The Avrami model provided a high fitting with the experimental data. The results have pointed out the slower kinetic for pyrimethamine sorption on chit-GLT compared to chit-Cu, in agreement with the reaction time obtained from calorimetry.
E.F.S. Vieira, A.R. Cestari, E.C.N. Lopes, L.S. Barreto, G.S. Lazaro, L.E. Almeida, Reactive & Functional Polymers xxx (2007) xxx-xxx

B1912 – Thermochemical study of 1-, 3- and 4-piperidinecarboxamide derivatives

The standard (p° = 0.1MPa) molar enthalpies of formation, at T = 298.15 K, in the gaseous phase, of three piperidinecarboxamide derivatives, namely 1-, 3- and 4-piperidinecarboxamide, were determined from their enthalpies of combustion and sublimation, obtained by static bomb calorimetry in oxygen and by Calvet microcalorimenty, respectively. The final results are analysed and discussed in terms of molecular structure.
M.A.V. Ribeiro da Silva, J.I.T.A. Cabral, Thermochimica Acta 453 (2007) 147-151

B1906 – Standard molar enthalpies of formation of 2-chloroquinoline, 4-chloroquinoline, 6-chloroquinoline and 4,7-dichloroquinoline by rotating-bomb calorimetry

The standard (p = 0.1 MPa) molar enthalpies of combustion, DcH m, for crystalline 2-, 4-, 6-chloroquinoline and 4,7-dichloroquinoline were determined at the temperature 298.15 K using a rotating-bomb combustion calorimeter. The standard molar enthalpies of sublimation, Dg crH m, at T = 298.15 K, were determined by Calvet microcalorimetry. The results were as follows: These values were used to derive the standard molar enthalpies of formation of the compounds in their crystalline and gaseous phases, respectively. The derived standard molar enthalpies of formation, in the gaseous state, are analysed in terms of enthalpic increments and interpreted in terms of molecular structure.
M.A.V. Ribeiro da Silva, M.A.R. Matos, L.M.P.F. Amaral, J. Chem. Thermodynamics 38 (2006) 49-55

B1904 – Biocatalysis using lipase encapsulated in microemulsion-based organogels in supercritical carbon dioxide

Lipases from Candida antarctica and Mucor miehei were encapsulated in lecithin water-in-oil (w/o) microemulsion-based organogels (MBG). These gels were formulated with either hydroxypropylmethyl cellulose (HPMC) or gelatin. The esterification of lauric acid and 1-propanol catalyzed by these MBGs was examined in supercritical carbon dioxide (scCO2; 35°C, 110 bar) as solvent for the substrates. The results were compared to those obtained with the reference substrate solvent isooctane. It turned out that the initial rates of this model reaction in scCO2 were higher than those observed in the reference system. Various parameters affecting the biocatalysis such as pressure, alcohol and acid chain length, and gel composition were investigated. Kinetic studies showed that the ester synthesis catalyzed by the immobilized C. antarctica lipase occurs via a Ping Pong Bi Bi mechanism in which only inhibition by excess of alcohol was identified. Values of all kinetic parameters were determined. In addition, experiments on the reusability of these gels in scCO2 were carried out and the state of water within the organogel was examined with the help of differential scanning calorimetry. The present study shows that biocatalysis using MBGs in scCO2 is a promising alternative to other bioconversion processes.
C. Blattner, M. Zoumpanioti, J. Kroner, G. Schmeer, A. Xenakis, W. Kunz, J. of Supercritical Fluids 36 (2006) 182-193

B1899 – Blood compatibility of novel poly( y-glutamic acid)/polyvinyl alcohol hydrogels

Sodium poly( y-glutamic acid) (PGA), awater-soluble and biodegradable polypeptide,was reacted with polyvinyl alcohol (PVA) to form hydrogel without any chemical treatment. The gelation occurred probably due to physical cross-linking of polymer chains by interpenetrating hydrogen bonding. From the results of thermal analysis, PGA/PVA exhibited better thermal stability than native PVA. Although the swelling ratio decreased with the increase of PGA content, however, the water resistance and retention were improved. The tensile strength of the PGA/PVA hydrogel membranes was about 15-30% lower than that of the native PVA, whereas the elongation was increased 2.0-2.6 times. The amount of protein adsorbed and platelets adhered on the PGA/PVA membranes were significantly curtailed with increasing PGA content, thereby showing improved blood compatibility. The as-fabricated hydrogels were proven to be non-cytotoxic evaluated in vitro by L-929 fibroblast incubation. Overall results demonstrate that the non-cytotoxic PGA/PVA hydrogels, due to better water resistance, mechanical properties and blood compatibility could be very promising candidates for blood-contacting medical devices
W-C. Lin, D-G. Yu, M-C. Yang, Colloids and Surfaces B: Biointerfaces 47 (2006) 43-49

B1735 – Study of mass transfer in oil-water-oil multiple emulsions by differential scanning calorimetry

A multiple emulsion of the type O1/W/O2 is studied experimentally by means of differential scanning calorimetry (DSC). The aim of this work is to characterize and measure the time-dependent changes within the emulsion. In particular, interest is focused to quantify the concentration changes in the internal and external phases of the O1/W/O2 multiple emulsion. In order to accomplish the objective, the measurement and analysis carried out by DSC are based on the crystallization behavior of the emulsion. A volume of a few mm3 is periodically removed from the O1/W/O2 multiple emulsion. The sample is submitted to steady cooling and the crystallization thermogram is recorded. The experimental data provided by the crystallization thermogram makes it possible to quantify the crystallized mass for both phases, the internal and the external. In addition, the composition in each phase can also be deduced from the thermogram. To deduce the composition, a diagram of crystallization temperatures is elaborated, employing several mixtures of known composition. In addition to the main objective previously mentioned, the influence of formulation parameters such as surfactant concentration in the aqueous phase and the mass ratio of the internal and external phases are also analyzed. The experimental results made it possible to conclude that a mass transfer took place from the internal phase toward the external phase; this transfer is caused by the composition difference on both sides of the aqueous membrane. In this work we analyzed the mass transfer in the multiple emulsion carried out by a composition gradient through the aqueous membrane. The most likely mechanism of mass transfer through the aqueous membrane is a solution-diffusion of tetradecane enhanced by the micelles of the surfactant Tween 20. The model of mass transfer confirms that the osmotic pressure difference controls the kinetics of tetradecane transfer. It is also confirmed that an increment of surfactant concentration in the aqueous phase allows a faster kinetics of the tetradecane transfer.
J.R. Avendano-Gomez, J.L. Grossiord, D. Clausse, Journal of Colloid and Interface Science 290 (2005) 533-545

B1732 – Solid state properties of 1,2-epoxy-3-(2-methoxyphenyloxy)-propane-valuable intermediate in non-racemic drug synthesis

Racemic 1,2-epoxy-3-(2-methoxyphenyloxy)-propane 1 undergoes spontaneous resolution upon crystallization. This fact is confirmed by coincidence of the IR spectra of racemic and scalemic crystalline samples of 1, by thermal analysis (single eutectic Vshape binary melting phase diagram), and X-ray analysis (space group P212121, Z = 4). Racemic 1 could be resolved into (S)-(+)- and (R)-( )-1 by a preferential crystallization procedure.
A. A. Bredikhin, E.I. Strunskaya, D.V. Zakharychev, D.B. Krivolapov, I.A. Litvinov and Z.A. Bredikhina, Tetrahedron: Asymmetry 16 (2005) 3361-3366

B1709 – Thermochemical studies of 1-hydroxyisoquinoline,5-hydroxyisoquinoline and 1,5-dihydroxyisoquinoline

The standard (p_ = 0.1 MPa) molar enthalpies of formation, DfH_m, for crystalline 1-hydroxyisoquinoline, 5-hydroxyisoquinoline and 1,5-diidroxyisoquinoline, were derived from the standard molar enthalpies of combustion, in oxygen, at the temperature 298.15 K, measured by static bomb-combustion calorimetry. The standard molar enthalpies of sublimation, Dg crH_m, at T = 298.15 K, were determined by Calvet microcalorimetry. The results were as follows: The derived standard molar enthalpies of formation, in the gaseous state, are analysed in terms of enthalpic increments and interpreted in terms of molecular structure.
M.A.V. Ribeiro da Silva, M.A.R. Matos, L.M.P.F. Amaral, J. Chem. Thermodynamics 37 (2005) 1312-1317

B1691 – DSC examinations on cataractous lens materials obtained by phacoemulsification

Modifications of lens proteins play a crucial role in the formation of cataract, which is among the leading causes of world blindness in the ageing population. Although modern cataract surgery by phacoemulsification is a very successful and safe procedure, the prevention of cataract formation would be a real breakthrough in this field of ophthalmology. The aim of our study was to analyse the thermal denaturation of the cataractous lens proteins by the method of differential scanning calorimetry (DSC), to understand cataract formation and to work on its prevention possibilities. Samples were obtained from cataract patients of different age, sex, patients with and without diabetes mellitus. Samples were obtained from lenses of mature degree and progredient degree of cataract as well. Previous DSC examinations were performed on manually extracted human cataractous lens materials, however to the best of our knowledge, this is the first study, in which DSC examinations were performed on lens materials obtained by the phacoemulsification technique, which gained acceptance world-wide in the last decade.
Zs. Biro, V. Nemes, G.A. Molnar, I. Wittmann, A. Ludany and D. Lörinczy, Journal of Thermal Analysis and Calorimetry 85 (2006) 261-265

B1600 – Calorimetric study and thermal analysis of crystalline nicotinic acid

As one primary component of Vitamin B3, nicotinic acid [pyridine 3-carboxylic acid] was synthesized, and calorimetric study and thermal analysis for this compound were performed. The low-temperature heat capacity of nicotinic acid was measured with a precise automated adiabatic calorimeter over the temperature rang from 79 to 368 K. No thermal anomaly or phase transition was observed in this temperature range. A solid-to-solid transition at T trs=451.4 K, a solid-to-liquid transition at T fus=509.1 K and a thermal decomposition at T d=538.8 K were found through the DSC and TG-DTG techniques. The molar enthalpies of these transitions were determined to be trs H m=0.81 kJ mol-1, fus H m=27.57 kJ mol-1 and d H m=62.38 kJ mol-1, respectively, by the integrals of the peak areas of the DSC curves.
S.X. Wang, Z.C. Tan, Y.Y. Di, F. Xu, M.H. Wang, L.X. Sun, T. Zhang, Journal of Thermal Analysis and Calorimetry 76 (2004) 335-342

B1584 – Polymorphic and thermodynamic study of indomethacin

Indomethacin is known to exhibit polymorphism. As a consequence the various forms have different solubilities and may have different bioavailabilities. This study has been carried out with the following techniques: calorimetry, differential scanning calorimetry (DSC), thermogravimetric analysis (TG), X-ray diffraction and thermomicroscopy. Two solid forms have been prepared and studied: their melting temperature and their enthalpy of fusion are determined. The heat capacity and heat content were measured vs. the temperature for these two solid forms and for the liquid phase. This is fundamental for the determination of the stable form. More of this, with a view to study phase diagrams of indomethacin with another compound (solvent or not), the knowledge of the Cp of the various forms is necessary for calculation of the liquidus curve, this allows to minimize the number of experiments.
B. Legendre, Y. Feutelais, Journal of Thermal Analysis and Calorimetry 76 (2004) 255-264

B1572 – Determination of solubility data by means of calorimetry

A calorimetric method for solubility determination is reported. A mathematical model is proposed to describe experimentally observed dissolution processes. The new technique allows the determination of the solubility curve in a wide temperature range by means of a single calorimetric run. The objective of the approach is not the high accuracy of the classical methods, but the minimization of experimental efforts. It is of particular interest for high-priced industrial products, e.g. pharmaceuticals or specialty chemicals. The method provides information about the dissolution kinetics and the dissolution heat as well. Based on solubility measurements carried out for various organic systems of fine chemicals, the experimental conditions affecting the solubility results are discussed in detail.
D. Sapoundjiev, H. Lorenz, A. Seidel-Morgenstern, Thermochimica Acta 436 (2005) 1-9

B1566 – The use of isothermal microcalorimetry to evaluate stability of ascorbic acid

R. Roskar, V. Kmetec, Journal of Pharmaceutical Sciences 25S1 (2005) S180-S182

B1520 – WIN 63843 polymorphs : crystal structure of form I and III and evidence of the enantiotropy

C. Vincent, J.M. Schneider, M.N. Petit and G. Coquerel, 30ieme JEEP (2005) 19-20

B1474 – Thermodynamic studies of monuron

Monuron (C9H11ClN2O; N,N-dimethyl-N'-(4-chlorophenyl) urea, CAS 150-68-5) was synthesized and the heat capacities of the compound were measured in the temperature range from 79 to 385 K with a high precision automated adiabatic calorimeter. No phase transition or thermal anomaly was observed in this range. The enthalpy and entropy data of the compound relative to the reference temperature 298.15 K were derived based on the heat capacity data. The thermodynamic properties of the compound were further investigated through DSC and TG analysis. The melting point, the molar enthalpy, and entropy of fusion were determined to be 447.6±0.1 K, 29.3±0.2 kJ mol-1, and 65.4 J K-1 mol-1, respectively.
L-G. Kong, Z.C. Tan, J-T. Mei, L-X. Sun, X-H. Bao, Thermochimica Acta 414 (2004) 131-135

B1470 – Thermodynamic study of ibuprofen by adiabatic calorimetry and thermal analysis

Molar heat capacities of ibuprofen were precisely measured with a small sample precision automated adiabatic calorimeter over the temperature range from 80 to 400 K. The polynomial functions of Cp,m (J K-1 mol-1) versus T were established on the heat capacity measurements by means of the least fitting square method. The functions are as follows: for solid ibuprofen, at the temperature range of 79.105 K
F. Xu, L-X. Sun, Z-C. Tan, J-G. Liang, R-L. Li, Thermochimica Acta 412 (2004) 33-37

B1419 – Importance of heat capacity determination in homogeneous nucleation : application to progesterone

Progesterone is known to exist under different crystallographic forms in the solid state. The thermodynamic stable form (I), melts at 129.2°C (402.35 K) under atmospheric pressure. After melting and cooling a metastable form (II) can be obtained which melts at 122°C (395.15 K). This uncommon behaviour can be explained with the theory of nucleation, only if heat capacity of the different forms are known.
B. Legendre, Y. Feutelais, G. Defossemont, Thermochimica Acta 400 (2003) 213-219

B1401 – Thermal analysis of anhydrous and hydrated cholesterol

Cholesterol constitutes the major component of most gallstones. it was identified and determined, in gallstones, issued from eleven patients, by thermal analysis: differential scanning calorimetry (DSC), with the use of the melting temperature and enthalpy, thermogravimetry (TG), with the mass loss of water. Anhydrous cholesterol (ChA) was characterized by two endothermic peaks (polymorphic, melting) and cholesterol monohydrate (ChH) by two endothermic peaks (dehydration, melting), too. ChA needle and ChH plate crystals were observed under polarizing light microscopy. the numerous stones obtained from nine patients were cholesterol stones: the ChA was higher 45 and lower 96%. ChH was present in stones of three patients
J. Kaloustian, A.M. Pauli, P. Lechene de la Porte, H. Lafont, H. Portugal, Journal of Thermal Analysis and Calorimetry 71 (2003) 341-351

B1360 – Microcalorimetric study of a proposed test reaction – the imidazole catalysed hydrolysis of triacetin. Temperature and imidazole concentration dependence

The imidazole catalysed hydrolysis of triacetin has recently [1] been proposed as a test reaction for isothermal heat conduction microcalorimeters affording validation and traceability for results derived from these instruments. The published values for ?RH, -91.7+3.0 kJ mol-1 and for the rate constant at 298 K, k, 2.8x10^(-6) ± 9.7x10^(-8) dm3 mol-1 s-1, were the results from an international inter- and intra-laboratory study. The protocol [1] for the conduct of the reaction specifies the reaction composition and a temperature of 298 K. Here, we report the temperature and imidazole concentration dependence of the rate constant for this reaction and the derived value of the activation energy; Ea=64.30±2.00 kJ mol-1. The value of ?RH is independent of temperature and a test for completeness of reaction (i.e. the reaction goes to completion at all temperatures and no effective equilibrium constant is determinable) is described.
A.K. Hills, A. E. Beezers, J.A. Connor, J.C. Mitchell, G. Wolf, F. Baitalow, Thermochimica Acta 386 (2002) 139-142

B1357 – Investigation in the quaternary system of (±) Malic Acid [(±)-1] and (±)-a-Methylbenzylamine [(±)-2]. Analysis of the chiral discrimination among crystallised phases.

F. Dufour, G. Perez, G. Coquerel, 28ème JEEP (2002) 67-70

B1356 – Dehydration mechanism and crystallisation behaviour of lactose

The dehydration mechanism of -lactose monohydrate was investigated by several techniques and interpreted on the basis of structural data. Whatever the dehydration conditions (heating or use of hygroscopic organic solvents), the departure of water molecules occurs cooperatively in channels parallel to the c axis of the initial structure. Subsequently, the reorganization leads to the closest packing (hygroscopic metastable form, LH) under heating or to the stable anhydrous form (LS), probably via a nucleation and growth process in ethanol. The use of acetone as dehydrating solvent on single crystals of -lactose monohydrate led to the unexpected formation of single crystals of the anomeric -lactose at room temperature, from which the crystal structure of -lactose could be accurately redetermined. Recrystallization experiments of anhydrous lactose allowed to prepare N-methylpyrrolidinone and DMSO solvates of -lactose
S. Garnier, S. Petit, G. Coquerel, Journal of Thermal Analysis and Calorimetry 68 (2002) 489-502

B1341 – Binary and ternary phase diagrams of two enantiomers in solvent systems

The binary phase diagram of the mandelic acid enantiomers and the binary and ternary phase diagrams of the same enantiomer(s) and water are studied as a typical enantiomeric system. The results of the experimental work performed are presented in detail and discussed both with regard to the applicability of different methods for solubility measurement and their importance for crystallization based enantioseparation. It will be shown that, in addition to classical methods differential scanning calorimetry (DSC) can be applied successfully for solubility determination. From the obtained phase diagrams various possibilities of gaining pure mandelic acid enantiomers from aqueous solutions are derived. The particular role of the eutectic composition in the enantiomeric system is emphasized.
H. Lorenz, A. Seidel-Morgenstern, Thermochimica Acta 382 (2002) 129-142

B1162 – Enthalpies of solution and crystallization of L-ascorbic acid in aqueous solution

Enthalpies of solution for (-ascorbic acid+water) have been measured in a SETARAM C80 D mixing calorimeter over the composition range of homogeneous solutions at temperatures of 298.15 K and 323.15 K. The results are reported in terms of excess molar enthalpies for {(xC6H8O6+(1-x)H2O} and molar enthalpies of solution for C6H8O6. The temperature and concentration dependence of the enthalpies of solution are given by a Redlich-Kister equation fitted with the experimental data. Enthalpies of crystallization of-ascorbic acid in aqueous solutions have been measured at the temperatures (293.15, 298.15, and 303.15) K during unseeded programmed crystallization. The molar enthalpies of crystallization for C6H8O6obtained experimentally agree well with those calculated from partial molar enthalpies of solution data of C6H8O6.
A. Dallos, É. Hajos-Szikszay and J. Liszi, J. Chem. Thermodynamics 30 (1998) 263-270

B1112 – Quantitation of amorphicity by microcalorimetry.

The amorphous state of solids is characterized by a higher chemical and physical reactivity and a hygroscopic behaviour. Furthermore processing of amorphous powders is often difficult, because of the instability. Fast crystallizations, precipitations and milling favour the formation of the amorphous state. Galenical processes like granulation, drying, lyophilization, mixing, may also induce amorphous regions in the drug products. X-ray diffraction techniques can be used for the determination of the amorphicity of drug raw materials or drug products. Unfortunately, 10% is the detection limit, which in normal cases can be attained. Amorphous substances undergo an exothermic crystallization at temperatures above the glass transition point. Water which is a plasticizer decreases the temperature of the glass transition point, allowing the crystallization to occur at lower temperatures. The crystallization energy is measure of by microcalorimetry. Examples show the influence of the choice of the experimental conditions, especially the influence of the amorphicity on the kinetic of the reaction. Critical steps are discussed for three different drug substances. Limits of detection in the magnitude of 1 % are possible using microcalorimetry.
D. Giron, P. Remy, S. Thomas, E. Vilette, Journal of Thermal Analysis 48 (1997) 465-472

B1110 – Mechanochemical preparation of drug-carrier solid dispersions.

The method of mechanical activation was used to obtain solid-state dispersions of some drugs in polyvinylpyrrolidone, polyethylene glycol and talc as carriers. Solid dispersions obtained by mechanical activation were found to have higher apparent solubilities and dissolution rates than mechanically activated drugs or their physical or eutectic mixtures with carriers used. It was shown by IR-spectroscopy and fluorescence measurements that mechanical treatment gave rise to an interaction between components which was apparently responsible for the solubilization effects observed.
T.P. Shakhtshneider, M.A. Vasilchenko, A.A. Politov, V.V. Boldyrev, Journal of Thermal Analysis 48 (1997) 491-501

B1032 – Observation of the melting process for ethyl p-aminobenzoate doped with eutectic mixture

In order to improve the reliability of purity measurements by differential scanning calorimetry (DSC), the melting process of a test material was studied using a system of ethyl p-aminobenzoate and n-butyl p-hydroxybenzoate. The eutectic mixture began melting accompanying the increase in temperature. After the minor component, p-hydroxybenzoate, had entirely melted in the eutectic mixture, it was confirmed by DSC measurement and solid phase-liquid phase titration that the major component, p-aminobenzoate, which remained as a solid, continued to dissolve into the eutectic mixture. In order to completely grasp the melting image of the test material, it was necessary to measure it from a sufficiently low temperature, and work up to the eutectic peak with the minor component. It was found that, by drawing up a solubility curve, the phenomenon in which p-aminobenzoate dissolves into the melted eutectic mixture is, in this system, close to the ideal solution based on Raoult's equation, and that the heat of mixing in an infinite dilution was indicated to be a small value of -1.9 J g-1. For that reason, the heat of fusion and the heat of dissolution coincided within the allowable error. Test materials that have been refined to a certain degree frequently include similar compounds as impurities, and this establishes an approximation of the heat of dissolution with the heat of fusion.
K. Yamamoto, H. Kitamura, M. Momota, K. Narita, Thermochimica Acta 267 (1995) 313-322

B1024 – A study on the interaction between some sustained release preparations and physiological saline by a microcalorimetric method

The thermal curves and the enthalpy changes of the interaction between some oral sustained release preparations (Contac, Fenbid and Benza sustained release capsules) and physiological saline have been measured at 298.15 K with a MS-80 standard Calvet microcalorimeter. The curves that recorded the changes of heat effect with time have clearly shown the sustained release action and process of the above preparations. A method for examining the sustained release action of sustained release preparations can be developed from the above experiments. The principle of application and the experimental procedure of this method have been expounded, and some results of the above experiments have also been discussed.
H-X. Zhao, B-H. Wang, Y-M. Zhang, Journal of Thermal Analysis 45 (1995) 27-33

B0955 – Characterization of the crystallinity of drugs : B02669, a case study

x
K.C. Thompson, J.P. Draper, M.J. Kaufman and G.S. Brenner, Pharmaceutical Research 11 (1994) 1362-1365

B0872 – The effects of the tabletting machine speed on physical characteristics of pharmaceutical powders

x
H. Drissi-Alami, M. Aroztegui, C. Lemagnen, D. Larrouture, L. Casahoursat, Journal de pharmacie de Belgique 48 (1993) 43-52

A2371 – Crystal structure and physicochemical properties of a new organic dihydrogenmonoarsenate

A new organic dihydrogenmonoarsenate (C3H9N2O2)H2AsO4 (abbreviate as ECAs) is prepared by reacting H3AsO4 with ethyl carbazate. This compound crystallizes in the monoclinic crystal system, space group P21/n. Unit cell parameters are a = 4.8370(2)A? , b = 24.6270(2)A? , c = 7.6311(5)A? , b = 92.948(4)8, with, Z = 4 and rm = 1.800 g cm 3. The structure is solved, using the direct methods and refined against F2 to a reliability R factor of 0.0475. The compound is characterized by infinite [H2AsO4]n n ribbons, parallel to the a-direction, connected by organic cations and forming layers localized at y = 0 and 1/2. The cohesion of the framework is ensured by hydrogen bonds N(O)–H O. The thermal properties of the compounds are investigated as well as the IR properties supported by group theoretical analyses.
Ahlem Chtioui, Latifa BenHamada, Saloua Belghith, Amor Jouini, Materials Research Bulletin 45 (2010) 1692–1695

A2370 – Removal of sulfonamide antibiotics from water: Evidence of adsorption into an organophilic zeolite Y by its structural modifications

Sulfonamide antibiotics are persistent pollutants of aquatic bodies, known to induce high levels of bacterial resistance. We investigated the adsorption of sulfadiazine, sulfamethazine, and sulfachloropyridazine sulfonamides into a highly dealuminated faujasite zeolite (Y) with cage window sizes comparable to sulfonamide dimensions. At maximal solubility the antibiotics were almost completely (>90%) and quickly (t<1min) removed from the water by zeolite. The maximal amount of sulfonamides adsorbed was 18-26% DW of dry zeolite weight, as evidenced by thermogravimetric analyses and accounted for about one antibiotic molecule per zeolitic cage. The presence of this organic inside the cage was revealed by unit cell parameter variations and structural deformations obtained by X-ray structure analyses carried out using the Rietveld method on exhausted zeolite. The most evident deformation effects were the lowering of the Fd-3m real symmetry in the parent zeolite to Fd-3 and the remarkable deformations which occurred in the 12-membered ring cage window after sulfadiazine or sulfachloropyridazine adsorption. After sulfamethazine adsorption, zeolite deformation caused a lowering in symmetry up to the monoclinic P2/m space group. The effective and irreversible adsorption of sulfonamides into organophylic Y zeolite makes this cheap and environmentally friendly material a suitable candidate for removing sulfonamides from water.
Ilaria Braschi, Sonia Blasioli, Lara Gigli, Carlo E. Gessa, Alberto Alberti, Annalisa Martucci, Journal of Hazardous Materials 178 (2010) 218–225

A2316 – Controlled drug release on amine functionalized spherical MCM-41

MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N2 physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41.
Agnes Szegedi, Margarita Popova, Ivan Goshev, Szilvia Klebert, Judit Mihaly, Journal of Solid State Chemistry 194 (2012) 257–263

A2306 – Carboxylic modified spherical mesoporous silicas ?s drug delivery carriers

The present study deals with the development and functionalization of mesoporous silica nanoparticles as drug delivery platforms. Spherical MCM-41 and SBA-15 silicas with different pore sizes (2.7 nm and 5.5 nm, respectively) were post-synthesis modified applying a new, two step process. The initial step was the modification with 3-amino-propyltriethoxysilane, and the next was the reaction with succinic anhydride in toluene in order to obtain carboxylic modified mesoporous carriers. The carboxylic-functionalized mesoporous materials were characterized by XRD, nitrogen physisorption, TEM, ATR FT-IR spectroscopy. The successful carboxylic functionalization was proved by the changes of the zeta potential of the mesoporous materials before and after modification. The parent and the carboxylic-modified MCM-41 and SBA-15 materials showed high adsorption capacity (approximately 50 wt.%, except for non-functionalized MCM-41) for sulfadiazine that possesses amino functional groups. Mesoporous structure peculiarities lead to different adsorption capacities on the carriers. In vitro release studies showed slower release rate of sulfadiazine from carboxylic modified MCM-41 and SBA-15 mesoporous particles compared to the non modified ones. Both non loaded and drug-loaded silica materials demonstrated no cytotoxicity on Caco-2 cell line. The functionalized mesoporous systems are appropriate drug delivery platforms due to their biocompatibility and the possibility to modify drug release.
Margarita D. Popova, Ágnes Szegedi, Iliyan N. Kolev, Judit Mihály, Borislav S. Tzankov, Georgi Tz. Momekov, Nikolai G. Lambov, Krassimira P. Yoncheva, International Journal of Pharmaceutics 436 (2012) 778– 785

A2241 – Modified SBA-15 as the carrier for metoprolol and papaverine: Adsorption and release study

A series of modified SBA-15 materials were applied in drug delivery systems. The internal surface of siliceous hexagonal structure of SBA-15 was modified with different amount of (3-mercaptopropyl)trimethoxysilane (MPTMS) and oxidized in the presence of hydrogen peroxide. The sulfonated material was loaded with metoprolol tartrate or papaverine hydrochloride. Both drugs indicated strong chemical interaction with modified mesoporous surface. The characteristic of the obtained materials was performed with XRD and DRUV-vis spectrometry, themogravimetry and nitrogen adsorption (BET) measurements. The obtained results show that modification of the mesoporous materials leads towards significant decrease of the drug delivery rate.
Michal Moritz, Marek Laniecki, Journal of Solid State Chemistry 184 (2011) 1761–1767

A2196 – Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release

MCM-41 and SBA-15 silica materials with spherical morphology and different particle sizes were synthesized and modified by post-synthesis method with 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, were carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N2 physisorption, thermal analysis, elemental analysis and FT-IR spectroscopy. Surface modification with amino groups resulted in high degree of ibuprofen loading and slow rate of release for MCM-41, whereas it was the opposite for SBA-15. The adsorbed drug content and the delivery rate can be predetermined by the choice of mesoporous material with the appropriate structural characteristics and surface functionality.
A. Szegedi, M.Popova, I.Goshev, J.Mihaly, Journal of Solid State Chemistry 184 (2011) 1201–1207

A2114 – Application of SBA-15 mesoporous material as the carrier for drug formulation systems. Papaverine hydrochloride adsorption and release study

SBA-15 mesoporous material was used as a matrix in three different drug formulations (powders, granules and tablets). Hydroxypropyl cellulose (HPC) and stearic acid (SA) were applied as modifiers of papaverine hydrochloride release from mesoporous carriers. The samples were characterized by thermogravimetry, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and nitrogen sorptometry at ? 196 °C. High pressure applied during the drug formulation (granules, tablets) decreases both specific surface area and porosity of SBA-15. The changes in BET surface area were also observed after drug deposition. The Korsmeyer–Peppas model was applied to evaluate the kinetics of papaverine hydrochloride release from hydroxypropyl cellulose- and stearic acid-containing drug formulations. The extended drug release resulted from slow diffusion of the active substance from micro- and mesoporous channels blocked by hydrophobic stearic acid and organic polymer.
Micha? Moritz, Marek ?aniecki, Powder Technology 230 (2012) 106–111

A2112 – SBA-15 mesoporous material modified with APTES as the carrier for 2-(3-benzoylphenyl)propionic acid

SBA-15 ordered mesoporous silica functionalized with (3-aminopropyl )triethoxysilane (APTES) was used as the carrier for anti-inflammatory drug: 2-(3-benzoylphenyl)propionic acid - ketoprofen. The surface of SBA-15 containing free silanol groups was modified with 3-aminopropyltriethoxysilane via post-synthetic reaction. Functionalization of the carrier with basic aminopropyl groups resulted in an ionic interaction with acidic ketoprofen. The samples of carriers and carrier-drug complexes were characterized by elemental analysis, TG, N2 adsorption, FTIR, DRUV spectroscopies and an in vitro drug release test. The adsorption of ketoprofen on modified mesoporous matrix was proportional to the amount of introduced aminopropyl groups. The maximum content of deposited drug in modified SBA-15 was close to 20 wt.%. After drug adsorption the reduction of BET surface area, pore volume and pore diameter of non-modified SBA-15 and aminopropyl-modified SBA-15 after drug adsorption were observed while the hexagonal array of siliceous matrix was well preserved. The release profiles of the aminopropyl-modified drug-containing SBA-15 exhibited prolonged release of ketoprofen in applied media. Tests performed in acidic solution (pH 1.2) showed the best pharmaceutical availability.
Micha? Moritz, Marek ?aniecki, Applied Surface Science 258 (2012) 7523– 7529

A1896 – Compatibility study between trandolapril and natural excipients used in solid dosage forms

Thermal analysis is an essential, analytic tool used in preliminary studies and preparation of new pharmaceutical formulations. This study was performed to investigate the possible interactions between trandolapril and three commonly used natural excipients, namely ?-lactose monohydrate, microcrystalline cellulose, and pregelatinized starch. The compatibility studies were carried out using thermoanalytic along with other complementary techniques. Differential scanning calorimetry and thermogravimetric analysis have proved that trandolapril is fully compatible with all the studied excipients until 100 °C. The complementary techniques used in this study were X-ray powder diffraction, Fourier transform-infrared spectroscopy, and scanning electron microscopy which confirmed the findings of thermal analysis.
Eleftheria Roumeli, Angelina Tsiapranta, Eleni Pavlidou, Georgios Vourlias, Kyriakos Kachrimanis, Dimitrios Bikiaris, Konstantinos Chrissafis, J Therm Anal Calorim, 2012

A1889 – Thermal, spectral, electrochemical and biologic characterization of new Pd(II) complexes with ligands bearing biguanide moieties

New complexes [Pd(HDMBG)2]Cl2 H2O, [PdL1]Cl2 0.5H2O and [PdL2]Cl2 1.5H2O (HDMBG: dimethylbiguanide, L1 and L2: ligands resulted from HDMBG, ammonia/hydrazine and formaldehyde template condensation) were synthesized and characterized. The features of complexes have been assigned from microanalytical, IR, UV–Vis and cyclic voltammetry data. The thermal transformations are complex processes according to TG and DTA curves including water and hydrochloric acid elimination, thermolysis processes leading to paracyanide formation as well as PdO decomposition, final product being palladium. Complexes were screened for their antimicrobial properties against some pathogenic Gram-positive and Gram-negative bacterial as well as fungal Candida albicans strains. The complexes exhibit specific antibacterial and/or antifungal activity, depending on their structure and the tested microbial strains. All complexes inhibit the microbial biofilm development on the inert substratum. It was also observed that PdCl2 complexation minimized their cytotoxic effect on the eukaryotic cells.
Mihaela Badea, Elica Iosub, Carmen Mariana Chifiriuc, Luminita Marutescu, Emilia Elena Iorgulescu, Veronica Lazar, Dana Marinescu, Coralia Bleotu, Rodica Olar, J Therm Anal Calorim, 2012

A1888 – Thermal study on complexes with Schiff base derived from 1,2,4-triazole as potential antimicrobial agents

In order to develop new metallo-antimicrobials the complexes of type MLCl nH2O ((1) M: Co, n = 0; (2) M: Ni, n = 2; (3) M: Cu, n = 2.5; (4) M: Zn, n = 0, HL: Schiff base derived from acetylacetone and 3-amino-4H-1,2,4-triazole) were synthesized by template condensation. The features of complexes have been assigned from microanalytical, IR and UV–Vis-NIR data. The species heating in air evidenced processes as melting, water and hydrochloride endothermic elimination as well as oxidative degradation of the Schiff base. The temperature ranges as well as modification in the electronic spectra of dehydrated intermediates indicate the presence of both coordination and crystallisation water molecules. The final product of decomposition was the most stable metal oxide as powder X-ray diffraction indicated.
Larisa Calu, Mihaela Badea, Denisa Falcescu, Daria Duca, Dana Marinescu, Rodica Olar, J Therm Anal Calorim, 2012

A1887 – Thermal study of new biologic active complexes with mixed ligands

Five new coordinative compounds that contain mixed ligands (4,40-bipyridine and methacrylate anion) were synthesized and characterized (elemental analysis, IR and UV–Vis spectroscopy, and thermal studies). The complexes are of the type [M(4,40-bipy)(C4H5O2)2] nH2O ((1) M:Mn, n = 0; (2) Co, n = 0.5; (3) M:Ni, n = 1.5; (4) M:Cu, n = 0.5; (5) M:Zn, n = 0.5; 4,40-bipy: 4,40-bipyridine; C4H5O2: methacrylate anion). All the tested complexes exhibited very low MIC values against Escherichia coli strains and one compound against Staphylococcus aureus. Besides the specific antimicrobial spectrum, these compounds also inhibited the microbial ability to colonize the inert surfaces, acting as potential anti-adherence and biofilm-controlling agents. The thermal behavior provided confirmation of the complexes’ compositions as well as the number and the nature of water molecules and the intervals of thermal stability.
Gina Vasile, Rodica Olar, Dana Marinescu, Angela Kriza, Luminita Marutescu , Mariana Carmen Chifiriuc, Veronica Lazar, Mihaela Badea, J Therm Anal Calorim, 2012

A1886 – Thermal and spectral studies of palladium(II) and platinum(IV) complexes with dithiocarbamate derivatives

Four newcoordination complexes of palladium(II) and platinum(IV) starting from bis(dimethylthiocarbamoyl) sulphide (L1) and bis(diethylthiocarbamoyl)disulphide (L2) were synthesized and characterized in solid state by elemental analysis, infrared and electronic spectroscopy as well as thermal analysis (TG/DTA). The complexes were formulated on the basis of experimental data as [Pd(Me2NCS2)2] (1), [Pt(Me2 NCS)2SCl4] 3H2O (2), [Pd(Et2NCS2)2] (3) and [Pt(Et2NCS)2 S2Cl4] 4H2O (4), respectively. TG experiments revealed the nature of complex species as hydrated (2 and 4) or anhydrous (1 and 3). Thermal decomposition of coordinated organic ligands occurs in one or two exothermic stages, the final residue being in all cases the free metal (Pd or Pt).
Valentina Uivarosi, Mihaela Badea, Victoria Aldea, Liviu Chirigiu, Rodica Olar, J Therm Anal Calorim, 2012

A1883 – Synthesis, spectral and thermal study on new Fe(III) complexes with N,N-dimethylbiguanide as antibacterial agents

New complexes [FeO(DMBG)]2 and [Fe(DMBG)2] Cl 0.5H2O (HDMBG: N,N-dimethylbiguanide) have been synthesized and characterized by microanalytical, IR and UV–Vis data. Electronic spectra of the complexes are characteristic for a tetrahedral stereochemistry, whilst the modifications in the IR spectra indicate the presence of the DMBG anion as chelate. The thermal decomposition investigated in air by thermal analysis confirmed the proposed formulas for the complexes and provided information concerning the modifications during heating and also the thermodynamic effects accompanying them. The thermal transformations are complex, according to TG and DTG curves including dehydration, hydrochloric acid elimination, oxidative degradation and condensation of –C=N– unit. The final product of decomposition was iron (III) oxide as powder XRD indicates. Complexes were screened for their antimicrobial properties against Gram-positive, Gram-negative bacterial, as well as fungal pathogenic strains. The results indicate that Fe(III) complexes exhibit an improved antibacterial activity against S. aureus and E. coli strains in comparison with free biguanide. The Fe(III) complexes also inhibit the ability of S. aureus, B. subtilis, P. aeruginosa and E. coli strains to colonize the inert substratum, accounting for their possible use as antibiofilm agents.
Mihaela Badea, Ana-Maria Crasanda, Mariana Carmen Chifiriuc, Luminita Marutescu, Veronica Lazar, Dana Marinescu, Rodica Olar, J Therm Anal Calorim, 2012

A1879 – New vanadyl complexes with metformin derivatives as potential insulin mimetic agents

Three new complexes with formula [VOL2] xH2O [(1) HL: N,N-dimethylbiguanide, x = 0.5; (2) HL:1-phenylbiguanide, x = 0; (3) HL: 1-(o-tolyl)biguanide, x = 0.5] were synthesised and characterised. The IR and UV–Vis spectral data indicate that these biguanide derivatives act as bidentate chelating anionic ligands and generate VO(II) complexes with a square–pyramidal stereochemistry. The thermal analysis (TG, DTA) elucidated the composition and also the number and nature of the water molecules.
Rodica Olar, Andreea Dogaru, Dana Marinescu, Mihaela Badea, J Therm Anal Calorim (2012) 110, 257–262

A1876 – Thermal behaviour of some new complexes with decaaza bismacrocyclic ligand as potential antimicrobial species

Novel complexes of type M2L(CH3COO)4 n H2O (M:Ni, n = 4; M:Cu, n = 2 and M:Zn, n = 0; L: ligand resulted in 1,2-phenylenediamine, 3,6-diazaoctane-1,8-diamine and formaldehyde template condensation) were synthesised and characterised. The features of complexes have been assigned from microanalytical, IR, UV–Vis, 1H NMR, EPR as well as magnetic data at room temperature. Processes as water elimination as well as oxidative degradation of both organic components (bismacrocycle and acetate) were observed. The final product of decomposition was metal (II) oxide as powder X-ray diffraction indicates.
Cristina Bucur, Mihaela Badea, Calu Larisa, Dana Marinescu, Maria Nicoleta Grecu, Nicolae Stanica, Mariana Carmen Chifiriuc, Rodica Olar, J Therm Anal Calorim (2012) 110, 235–241

A1874 – Synthesis, characterization, and thermal decomposition of new copper (II) complex compounds with chlorhexidine

Three new copper (II) complex compounds with chlorhexidine (CHX) as ligand have been prepared and characterized by elemental and thermogravimetrical analyses, molar conductances, infrared, and UV–Vis spectra. Chlorhexidine acts as neutral tetradentate NNNN donor, coordinating through the four imine nitrogen atoms. Based on the experimental data the following formulas have been proposed for the complex compounds: [Cu(CHX)](NO3)2 (1), [Cu2(CHX)Br2Cl2] 4H2O (2), and [Cu(CHX)Cl]Cl (3). Thermal decomposition evidenced dehydration (complex 2), anionic moieties release and the ligand cleavage with chlorobenzene moieties removal for all complexes. The final residue is in all cases copper oxide. Antibacterial and antifungal activities of the complexes have been determined in vitro, by the cup-plate agar diffusion method, against Escherichia coli, Staphyloccocus aureus, and Candida albicans. The complexes present an activity comparable to that of chlorhexidine, the most active being [Cu2(CHX)Br2Cl2] 4H2O.
Mihaela Badea, Rodica Olar, Monica Ilis, Rodica Georgescu, Mirela Calinescu, J Therm Anal Calorim, 2012

A1873 – Synthesis and characterization of some vanadyl complexes with flavonoid derivatives as potential insulin-mimetic agents

Two new complexes with formula VOL2 nH2O ((1) L: 40,5,7-trihydroxyflavone-7-rhamnoglucoside (naringin), n = 8; (2) L: 30,40,7-tris[O-(2-hydroxyethyl)]rutin (troxerutin), n = 0) were synthesised and characterised. The IR and UV–Vis spectral data indicate that these flavones act as bidentate chelating ligands and generate VO(II) complexes with a square-pyramidal stereochemistry. The thermal analysis (TG, DTA) elucidated the composition and also the number and nature of the water molecules. The thermal behavior indicates also a strong interaction between oxovanadium (IV) and these oxygen donor ligands.
Mihaela Badea, Rodica Olar, Valentina Uivarosi, Dana Marinescu, Victoria Aldea, J Therm Anal Calorim (2012) 107, 279–285

A1872 – Studies on thermal behavior of some antibacterial copper (II) complex compounds with a dibiguanide derivative ligand

The thermal behavior of six complex compounds of Cu(II) with chlorhexidine as ligand was investigated. The complexes are obtained from chlorhexidine diacetate and copper (II) chloride, bromide and acetate, respectively, in metal:ligand molar ratio 1:1 and 2:1. Thermal decomposition evidenced several well-defined steps as desolvation, anionic moieties release and the ligand cleavage for all complexes. The final residue is in all cases copper (II) oxide.
Rodica Olar, Mihaela Badea, Monica Ilis, Ticuta Negreanu-Pirjol, Mirela Calinescu, J Therm Anal Calorim, 2012

A1680 – Physicochemical characterization and decomposition kinetics of trandolapril

The purpose of this work was to study the physicochemical properties of trandolapril, to perform a detailed kinetic study of its decomposition and also to evaluate its thermal stability in order to provide the essential tools to design a thermal destruction method for expired trandolapril-based drugs. Trandolapril was characterized with FTIR, XRPD and SEM and its thermal behaviour was studied with DSC and TGA in dry air and nitrogen flows. The decomposition process was also followed by Py-GC–MS, the activation energy was calculated with isoconversional methods and the reaction model was determined with model-fitting method. Trandolapril is stable until the onset of its melting (110 ?C) in both nitrogen and dry air environments. Thermal degradation of trandolapril can be described by two consecutive mechanisms of n-th order with activation energies 97.4 and 180.0 kJ/mol respectively. Trandolapril reaches zero residual at 510 and 560 ?C in nitrogen and dry air flow respectively. The detailed analysis of decomposition mechanism allows the industry to design integrated thermal destruction processes for expired trandolapril-based drugs. The results of Py-GC–MS agree with the theoretical calculations of thermal analysis techniques, which highlights that the different techniques used in this work are complementary and equally important.
E. Roumeli, A. Tsiapranta, K. Kachrimanis, D. Bikiaris, K. Chrissafis, Thermochimica Acta 539 (2012) 92– 99

A1668 – Effects of calcination temperature on the drug delivery behaviour of Ibuprofen from hydroxyapatite powders

The effects of heat treatment time and temperature on the delivery behaviour of Ibuprofen from hydroxyapatite particles were investigated in this study. The drug release was seen to follow Fickian diffusion for the initial period of release for all heat treatment conditions. The gradient of Fickian release increased with (1) increasing crystallite size, attributed to the decreasing amount of boundary area, and (2) with decreasing surface area, due to the reduction in porosity and hence tortuosity within the apatite particles. This study has shown that altering the heat treatment conditions used to calcine hydroxyapatite may alter its drug delivery abilities, whereby calcination temperature was noted to influence the drug release behaviour to a greater extent than calcination time.
Amanda J. Melville, Luis M. Rodr?guez-Lorenzo, John S. Forsythe, J Mater Sci: Mater Med (2008) 19:1187–1195

A1584 – Thermal behaviour of new Cu(II) complexes with Schiff bases functionalised with 1,3,5-triazine moieties as potential antibacterial agents

New complexes of type [Cu(L1)2(OH2)] 4H2O (1), [Cu(L2)(OH2)] 0.5H2O (2) and [Cu3(L3)2(OH2)3] 0.5H2O (3) were synthesized by [1 ? 1], [1 ? 2] and [1 ? 3], respectively, template condensation of 2,4,6-triamino-1,3,5-triazine and salicylic aldehyde in the presence of copper(II). The features of complexes have been established from microanalytical, IR and UV–Vis data. The thermal analyses have evidenced the thermal intervals of stability and also the accompanying thermodynamic effects. Processes as water elimination and oxidative degradation of the organic ligands were observed. After water elimination, complexes revealed a similar thermal behaviour. The final product of decomposition was copper(II) oxide as powder X-ray diffraction indicated.
Rodica Olar, Mihaela Badea, Dana Marinescu, Ramona Mardale, J Therm Anal Calorim (2011) 105, 553–557

A1583 – Thermal behaviour of some new complexes with bismacrocyclic ligands as potential biological active species

Novel complexes of type [M2LCl4] nH2O ((1) M:Ni, n = 5; (2) M:Cu, n = 0 and (3) M:Zn, n = 2; L: ligand resulted from 1,2-phenylenediamine, 3,6-diazaoctane-1,8-diamine and formaldehyde template condensation) were synthesised and characterised. The features of complexes have been assigned from microanalytical, IR and UV–Vis data. The thermal analyses have evidenced the thermal intervals of stability and also the thermodynamic effects that accompany them. Processes as water or hydrochloric acid elimination as well as oxidative degradation of the organic ligand were observed. Complexes display a different thermal behaviour as result of dissimilar chemical interaction of metal ions with chloride anions. The final product of decomposition was metal(II) oxide as powder X-ray diffraction indicated.
Rodica Olar, Mihaela Badea, Dana Marinescu, Larisa Calu, Cristina Bucur, J Therm Anal Calorim (2011) 105, 571–575

A1582 – Synthesis and characterization of some vanadyl complexes with flavonoid derivatives as potential insulin-mimetic agents

Two new complexes with formula VOL2 nH2O ((1) L: 40,5,7-trihydroxyflavone-7-rhamnoglucoside (naringin), n = 8; (2) L: 30 ,40,7-tris[O-(2-hydroxyethyl)]rutin (troxerutin), n = 0) were synthesised and characterised. The IR and UV–Vis spectral data indicate that these flavones act as bidentate chelating ligands and generate VO(II) complexes with a square-pyramidal stereochemistry. The thermal analysis (TG, DTA) elucidated the composition and also the number and nature of the water molecules. The thermal behavior indicates also a strong interaction between oxovanadium (IV) and these oxygen donor ligands.
Mihaela Badea, Rodica Olar, Valentina Uivarosi, Dana Marinescu, Victoria Aldea, J Therm Anal Calorim (2012) 107,279–285

A1581 – Thermal degradation behavior of some ruthenium complexes with fluoroquinolone derivatives as potential antitumor agents

Three new complexes with ligands belong to the fluoroquinolone class having the general formula [RuL2 Cl2]Cl nH2O ((1) L: norfloxacin (nf), n = 4; (2) L: ciprofloxacin (cp), n = 3; (3) L: enrofloxacin (enro), n = 5) were synthesized and characterized by chemical analysis UV–Vis and IR spectroscopy. In all complexes fluoroquinolone derivative acts as bidentate chelate ligand. The thermal behavior steps were investigated in synthetic air flow. The thermal transformations are complex processes according to TG and DTG curves including dehydration, quinolone derivative degradation, as well as RuCl3 conversion in RuO2.
Valentina Uivarosi, Mihaela Badea, Rodica Olar, Dana Marinescu, Teodor Octavian Nicolescu, George Mihai Nitulescu, J Therm Anal Calorim (2011) 105, 645–650

A1580 – Thermal behavior of some vanadyl complexes with flavone derivatives as potential insulin-mimetic agents

Two new complexes having general formula VOL2 nH2O[(1) L: 5-hydroxyflavone, n = 1; (2) L: chrysin, n = 4] were synthesized and characterized. Based on IR and electronic data we concluded that studied flavones act as bidentate ligands in complexes with metallic ion coordinated in a square-pyramidal stereochemistry. The thermal analysis (TG, DTA) elucidated the composition and also the number and nature of the water molecules. The thermal behavior also indicated strong interactions between oxovanadium (IV) and these oxygen donor ligands
Mihaela Badea, Rodica Olar, Valentina Uivarosi, Dana Marinescu, Victoria Aldea, Stefania Felicia Barbuceanu, George Mihai Nitulescu, J Therm Anal Calorim (2011) 105, 559–564

A1554 – Biodegradability of sol–gel silica microparticles for drug delivery

The biodegradability of porous sol–gel silica microparticles in physiological buffers has been investigated using a USP4 flow-through dissolution tester. In the open configuration, which most closely models in-vivo conditions, the particles dissolved rapidly at pH 7.4, with a rate dependent on the surface area and media flow rate. In the closed configuration, the fastest dissolving 4 mg silica sample was almost completely dissolved in 100 mL of buffer after 36 h. The initial dissolution rates appeared relatively linear but dropped off as dissolved SiO2 concentrations approached 20–25 ppm. Addition of serum proteins acted to slow dissolution by 20–30%, suggesting a slower degradation in vivo. Silica microparticles administered for controlled release drug delivery would therefore be expected to be eliminated relatively rapidly from the body, depending on the sample size and local fluid flow conditions.
Kim S. Finnie, Daniel J. Waller, Francois L. Perret, Anwen M. Krause-Heuer,Hui Q. Lin, John V. Hanna, Christophe J. Barbe, J Sol-Gel Sci Technol (2009) 49,12–18

A1498 – From compressibility to structural investigation of sodium dodecyl sulphate — Part 2: A singular behavior under pressure

Investigations were carried out to elucidate the compression behavior of a powdered surfactant, sodium dodecyl sulphate (SDS), based on a comparison with the main component of a detergent formulation, i.e. the chorine provider (DCCNa). The energetic analysis based on the compression cycles highlighted a lower compressibility of SDS compared with DCCNa, especially due to its worse packing ability, larger elasticity and bad cohesion ability. Also, it pointed out that the pycnometric density seemed to be overrun under pressure whereas a residual porosity had been evidenced in the expanded tablets. DSC/DTA analysis, Raman spectroscopy as well as powder X-ray diffraction refuted the hypothesis of a physico-chemical transformation of SDS under pressure. This was in accordance with the morphology of the SDS particles, quite unchanged after compression. The pycnometric density measurements have been improved; firstly, it allowed to properly express the compaction ratio of the ejected SDS tablets, and secondly, it led to conclude to a reversible intrinsic compressibility for pressures higher than 50 MPa, explained by the predominant elastic behavior of SDS.
Florence Chantraine, Marylène Viana, Sophie Cazalbou, Nelly Brielles, Olivier Mondain-Monval, Christelle Pouget, Paul Branlard, Gilles Rubinstenn, Dominique Chulia, Powder Technology 177 (2007) 41–50

A1186 – Chitosan kills bacteria through cell membrane damage

The bactericidal activity of chitosan (CS) acetate solution against Escherichia coli and Staphylococcus aureus was evaluated by the enumeration of viable organisms at different incubation times. Morphologies of bacteria treated with CS were observed by transmission electron microscopy (TEM). The integrity of the cell membranes of both species and the permeabilities of the outer membrane (OM) and inner membrane (IM) of E. coli were investigated by determining the release from cells of materials that absorb at 260 nm, changes in the fluorescence of cells treated with the fluorescent probe 1-N-phenylnaphthylamine (NPN) and release of cytoplasmic beta-galactosidase activity. In addition, the interaction of CS with synthetic phospholipid membranes was studied using gel permeation chromatography (GPC), UV-VIS spectrophotometery, Fourier-transform infrared spectroscopy (FT-IR) and thermal analysis. Results showed that CS increased the permeability of the OM and IM and ultimately disrupted bacterial cell membranes, with the release of cellular contents. This damage was likely caused by the electrostatic interaction between NH3 + groups of CS acetate and phosphoryl groups of phospholipid components of cell membranes.
H. Liu, Y. Du, X. Wang, L. Sun, International Journal of Food Microbiology 95 (2004) 147-155

A1115 – TG-MS characterisation of pig bone in an inert atmosphere

A challenge for forensic examiners is the ageing and characterisation of bone fragments or decomposed skeletal remains. Due to the sensitivity of thermal methods to morphological states, thermal analysis has been selected as a technique which could overcome the difficulties. In this preliminary study, TG-MS was applied to the characterisation of bone fragments derived from the compact bone of pig rib specimens. TG-MS curves were collected by heating bone samples to 1000°C in an argon atmosphere. Under these conditions, both the organic and inorganic phases decomposed, producing a variety of organic fragments and carbon dioxide. Pyrolysis of the organic phase, which is composed predominantly of collagen, occurred resulting in the observation of ion fragments up to 110 amu. Selected fragments were monitored and their observation is discussed in terms of the decomposition of both the collagen phase and the inorganic carbonated hydroxyapatite phase.
A. Onishi, P.S. Thomas, B.H. Stuart, J.P. Guerbois and S. Forbes, Journal of Thermal Analysis and Calorimetry 88 (2007) 405-409

A1108 – Adiabatic calorimetry and thermal analysis on acetaminophen

Molar heat capacities of acetaminophen were precisely measured with a small sample precision automated adiabatic calorimeter over the temperature range from 80 to 330 K. A solid-solid transition at 149.96 K was found from the Cp,m-T curve. The polynomial functions of Cp,m(J K-1 mol-1) vs. T were established on the heat capacity measurements by means of the least square fitting method. Thermal decomposition processes of acetaminophen have been studied by thermogravimetry. And the thermal decomposition kinetics parameters, such as activation energy E, pre-exponential factor A and reaction order n, were calculated by TG-DTG techniques with the Freeman-Carroll method, Kissinger method and Ozawa method. Accordingly the thermal decomposition kinetics equation of acetaminophen is expressed as: dalpha/dt=2.67 x 10^7 x exp(-89630/RT) x (1-alpha)^0.23. The process of fusion has been investigated through DSC. The melting point, molar enthalpy and entropy of fusion are to be (441.89 ± 0.04) K, 26.49 ± 0.44 kJ mol-1 and 59.80 ± 1.01 J K-1 mol-1, respectively.
F. Xu, L. X. Sun, Z. C. Tan, J. G. Liang and T. Zhang, Journal of Thermal Analysis and Calorimetry 83 (2006) 187-191

A1064 – Synthesis and evaluation of the mucoadhesivity of a CD-chitosan derivative

Combining mucoadhesive characteristics of a biodegradable polymer such as chitosan with the potential to enhance drug release by increasing the solubility of poorly water-soluble drugs has great potential for pharmaceutical technology and drug delivery design. Polymeric delivery systems have been extensively researched in an attempt to achieve modified drug release. Cyclodextrins (CD) offer an alternative approach. These cyclic oligosaccharides have the ability to form non-covalent complexes with a number of drugs altering their physicochemical properties. In the continuing challenge to improve the properties of delivery systems, this paper focuses on the modification of chitosan by introducing beta-cyclodextrin and to test the mucoadhesive strength and inclusion properties of this synthesised cyclodextrin-polymer. beta-Cyclodextrin was successfully grafted onto a chitosan chain polymer with a cyclodextrin grafting yield of 7% and a CD-chitosan yield of 85%. Although the complexation of (+)-catechin by the grafted beta-CD was found to be about five times weaker than that by the beta-CD monoaldehyde and natural beta-CD, the inclusion properties of the chitosan-CD remain promising. The mucoadhesive properties of chitosan-CD were compared to that of pectin (reference) and the parent chitosan with the use of a tensile separation test. The chitosan-CD showed mucoadhesive strengths of 12% stronger than pectin, but 13.5% weaker than the parent chitosan. The synthesised chitosan-CD-polymer exhibits characteristics of a possible mucoadhesive drug delivery system with some inclusion properties from beta-cyclodextrin.
J.P. Venter, A.F. Kotzé, R. Auzély-Velty, M. Rinaudo, International Journal of Pharmaceutics 313 (2006) 36-42

A1040 – Spectral and structural study of two acceptor-substituted pyridinium-betaines of squaric acid: Promising chromophores for nonlinear optical applications

Two acceptor-substituted chromophores (3- and 4-benzoylpyridinium-betaines of squaric acid) were characterized by means of thermogravimetric analysis and UV-vis and IR spectra. The experiment is supported by theoretical predictions undertaken at different levels of approximation (MP2 and DFT/B3LYP). The results of the optimized molecular structure are presented and compared with the X-ray diffraction data for both chromophores studied. Generalized atomic polar tensor (GAPT) model was chosen for calculation of atomic charges of studied species. The charge distribution over fragments indicates that strongly polarized systems are present. Harmonic vibrational frequencies of the molecules were evaluated theoretically using B3LYP/6-311G** level. The nonlinear optical efficiency of both chromophores was estimated by molecular parameters such as absorption maxima in various solvents of different polarity, ground state dipole and difference between ground and excited state dipole moments. A static hyperpolarizability for 4-benzoyl chromophore was provided from EOAM experiment for a dioxane solution. Combined with the noncentrosymmertic crystal structure of the same isomer and the exceptional thermal stability of both species, these studies gave evidences for their reliability as nonlinear optical materials.
T. Kolev, B. Stamboliyska, D. Yancheva, Chemical Physics 324 (2006) 489-496

A0984 – Studies on a new carrier of trimethylsilyl-modified mesoporous material for controlled drug delivery

To better control drug delivery rate, a simple and effective approach has been developed for controlled drug delivery carrier system through one-step surface modification of the ibuprofen-impregnated silica MCM-41 with 1, 1, 1, 3, 3, 3-hexamethyldisilazane (HMDS). The 29Si MAS NMR characterization demonstrated that different contents of trimethylsilyl (TMS) groups were successfully grafted onto the samples modified with different silylation times. The results obtained from in vitro tests exhibited that the introduction of TMS groups greatly retarded the ibuprofen release rate. Even after in vitro test for 48 h, only 75% of the impregnated ibuprofen could be released from the modified sample with TMS groups content of 14.5% (related to the total silicon atoms). However, the release of ibuprofen could be completed just after about 1 h from the pure silica MCM-41 under the same release conditions. Furthermore, the release rate of ibuprofen could be well modulated by changing the grafted content of TMS groups, and was found to decrease with increasing grafted amount of TMS groups.
Q. Tang, Y. Xu, D. Wu, Y. Sun, J. Wang, J. Xu, F. Deng, Journal of Controlled Release 114 (2006) 41-46

A0931 – Cefdinir: A comparative study of anhydrous vs. monohydrate form Microstructure and tabletting behaviour

Anhydrous cefdinir (AC) vs. monohydrated cefdinir (MHC) was compared in order to be used as antimicrobial in therapeutics. Different techniques have been used to characterize physically AC and MHC, and also a complete microstructural analysis of raw materials was carried out. Cefdinir and Maltodextrin QDM® 500 (3:2) formulations were compressed in order to obtain tablets with typical dose of Cefdinir, i.e. 300 mg. Dissolution profiles were obtained for both AC and MHC tablets. Finally tablet X-ray diffraction was performed to ensure the stability of the monohydrated form after tabletting being clearly different in both AC and MHC crystals. AC crystal structure was agreed with the known pattern of anhydrous Cefdinir described in the literature. Microstructural analysis showed large differences in specific surface area (SSA), confirmed by mercury intrusion. Crystal structures of both AC and MHC were stable under mixing, compression and storing processes. Dissolution profiles were faster for hydrate form, probably related to microstructural properties of the crystal which remained after tabletting. In conclusion, it is possible to isolate Cefdinir in two forms anhydrous and monohydrate, well characterized and differentiated. The use of this later improves dissolution of tablet dosage form due to the lack of interconversion during tablet manufacture.
W. Cabri, P. Ghetti, M. Alpegiani, G. Pozzi, A. Justo-Erbez, J.I. Pérez-Martinez, R. Villalon-Rubio, M.C. Monedero-Perales, A. Munoz-Ruiz, European Journal of Pharmaceutics and Biopharmaceutics 64 (2006) 212-221

A0887 – Crystal structure, thermal analysis and IR spectrometric investigation of L-tyrosine hydrazide diphosphate monohydrate

The monoclinic crystal structure of (C9H15N3O2)2P2O7.H2O denoted DLTHDP [a = 14.626(1), b = 6.1990(2), c = 14.562(1) Å, beta = 97.289(3)°, Z = 2, monoclinic P21, Dcal = 1.508, Dmes = 1.49 g cm-3] has been solved using direct methods and refined to a reliability factor R = 4.37% for 2079 independent reflections. The DLTHDP structure can be described by infinite polyanions [P2O7 H2O]n 4n- organized in chains parallel to the b-direction and located at z = 1/2, alternating with organic cations associated in ribbons spreading along the a-direction. Multiple hydrogen bonds originating from amine, hydroxyl groups and water molecules donors [N-H....O(N) and O(W)-H....O] connect the different components of the lattice. The IR data of DLTHDP is reported and discussed according to the theoretical group analysis and by comparison with IR results of similar compounds. The coupled thermogravimetric analysis (TGA)-differential thermal analysis (DTA) thermal study shows the departure of one water molecule, confirming the hydrated character of this compound.
A. Gharbi, T. Guerfel, A. Jouini, Materials Research Bulletin 41 (2006) 2024-2034

A0879 – The dynamic process in the formation of Tyr/LDH nanohybrids

The dynamic intercalation process of tyrosine (Tyr) into layered double hydroxide (LDHs) by co-precipitation method was investigated by powder X-ray diffractometry, Fourier transform infrared spectroscopy, specific surface area measurements, pore size distributions as well as thermal analysis. The nanohybrids were found to have an expanded layered structure indicating that amino acid anions were intercalated into the gallery space. Two kinds of arrangements such as mono- or bilayers of the tyrosinate anions could be deduced from the XRD patterns. The arrangement changed from monolayer to bilayer, then again to monolayer with increasing aging time of the synthesis solution. The diffraction intensity increased then decreased with aging time, because of the variation in the orientation and ordering of the particles. TG analysis and the varying M2+/M3+ results revealed that the amount of tyrosinate anions in the gallery first decreased then increased with the increase of aging time. In addition, the morphology results showed that the degree of ordering also increased then decreased with aging time. On all accounts, the intercalation of the tyrosinate anions was a typical dynamic process. At the beginning numerous biomolecules entered the gallery space, giving rise to increased basal spacings and BET surface areas. Later the increase of aging time led to the escape of amino acid anions from the gallery space, hence to the decrease of basal spacing and surface areas.
Shu-Ping Li, Colloids and Surfaces A: Physicochem. Eng. Aspects 290 (2006) 56-61

A0873 – Fluorine-substituted hydroxyapatite scaffolds hydrothermally grown from aragonitic cuttlefish bones

Porous hydroxyapatite scaffolds with different levels of fluorine substitution (46% and 85%) on the OH sites were produced via hydrothermal transformation of aragonitic cuttlefish bones at 200°C and calcination at temperatures up to 1200°C. The increasing level of F substitution reduces the kinetics and probably the yield of the reaction. The incorporation of F in the lattice of hydroxypatite caused a lowering of the unit cell volume due to reduction of the length of the a-axis. The crystallites formed were close in size to bone-like apatite and were orientated along the a-axis rather than the c-axis. There was evidence of AB-type carbonated apatite.
S. Kannan, J.H.G. Rocha, S. Agathopoulos, J.M.F. Ferreira, Acta Biomaterialia 3 (2007) 243-249

A0868 – Heat capacity and standard molar enthalpy of formation of crystalline 2,6-dicarboxypyridine (C7H5NO4)

Low-temperature heat capacity Cp,m of 2,6-dicarboxypyridine (C7H5NO4; CAS 499-83-2) was precisely measured in the temperature range from (80 to 378) K with a high precision automated adiabatic calorimeter. No phase transition or thermal anomaly was observed in this range. The thermodynamic functions [HT - H298.15] and [ST - S298.15] were calculated in the range from (80 to 378) K. The standard molar enthalpy of combustion and the standard molar enthalpy of formation of the compound have been determined, ?cHm°(C7H5NO4, cr) = - (2741.41 ± 0.49) kJ.mol-1 and ?fHm°(C7H5NO4, cr) = - (727.74 ± 1.50) kJ.mol-1, by means of a precision oxygen-bomb combustion calorimeter at T = 298.15 K. The thermodynamic properties of the compound were further investigated through differential scanning calorimeter (DSC) and the thermogravimetric (TG) analysis.
Q. Shi, Z-C. Tan, Y-Y. Di, X-C. Lv, B. Tong, Z-H. Zhang, L-X. Sun, T. Zhang, J. Chem. Thermodynamics 38 (2006) 1701-1705

A0713 – Kinetic studies on the pyrolysis of chitin and chitosan

The thermal degradation of chitin and chitosan have been studied by using simultaneous TG and DSC in nitrogen atmosphere. The model-free iso-conversional method has been employed to evaluate the activation energies as a function of the extent of degradation. The obtained dependencies are interpreted in terms of degradation mechanisms. Under nitrogen, the thermal degradation of chitin and chitosan follows a random scission pathway, which is initiated at weak links. The activation energies of thermal degradation of chitin are constant and this process follows 1.23 order reaction. As for chitosan, the activation energies of thermal decomposition are obviously dependent on the extent of conversion. The pyrolysis reaction of chitosan is analysed by using a distributed activation energy model (DAEM) because the residual N-acetylated side-chains are randomly distributed on the chitosan main chains. Also, the parameters of the DAEM are evaluated.
T. Wanjun, W. Cunxin, C. Donghua, Polymer Degradation and Stability 87 (2005) 389-394

A0572 – Evaluation of a new copper(II)-curcumin complex as superoxide dismutase mimic and its free radical reactions

A mononuclear (1:1) copper complex of curcumin, a phytochemical from turmeric, was synthesized and examined for its superoxide dismutase (SOD) activity. The complex was characterized by elemental analysis, IR, NMR, UV-VIS, EPR, mass spectroscopic methods and TG-DTA, from which it was found that a copper atom is coordinated through the keto-enol group of curcumin along with one acetate group and one water molecule. Cyclic voltammetric studies of the complex showed a reversible Cu2+/Cu+ couple with a potential of 0.402 V vs NHE. The Cu(II)-curcumin complex is soluble in lipids and DMSO, and insoluble in water. It scavenges superoxide radicals with a rate constant of 1.97 x 10^5 M-1 s-1 in DMSO determined by stopped-flow spectrometer. Subsequent to the reaction with superoxide radicals, the complex was found to be regenerated completely, indicating catalytic activity in neutralizing superoxide radicals. Complete regeneration of the complex was observed, even when the stoichiometry of superoxide radicals was 10 times more than that of the complex. This was further confirmed by EPR monitoring of superoxide radicals. The SOD mimicking activity of the complex was determined by xanthine/xanthine oxidase assay, from which it has been found that 5 Ag of the complex is equivalent to 1 unit of SOD. The complex inhibits radiation-induced lipid peroxidation and shows radical-scavenging ability. It reacts with DPPH radicals with rate constant 10 times less than that of curcumin. Pulse radiolysis-induced one-electron oxidation of the complex by azide radicals in TX-100 micellar solutions produced strongly absorbing (¨500 nm) phenoxyl radicals, indicating that the phenolic moiety of curcumin remained intact on complexation with copper. The results confirm that the new Cu(II)-curcumin complex possesses SOD activity, free radical neutralizing ability, and antioxidant potential. Quantum chemical calculations with density functional theory have been performed to support the experimental observations.
A. Barik, B. Mishra, L. Shen, H. Mohan, R.M. Kadam, S. Dutta,H.-Y. Zhang, K.I. Priyadarsini, Free Radical Biology & Medicine 39 (2005) 811 - 822

A0514 – Decomposing or subliming? An investigation of thermal behavior of l-leucine

The thermal behavior of l-leucine under inert conditions was investigated by TGA, FTIR and TG-FTIR. The TG results showed that only one mass loss stage of more than 99% happened when l-leucine was under program heating with temperature ranging from 30 to 600°C. The apparent activation energy, pre-exponential factor and the most probable model function were obtained by using of master plots method. The results of kinetic study showed that the decrease in mass of l-leucine was due to subliming rather than decomposing. And this was proved by the FTIR spectrum analysis and the directly observed subliming phenomenon. The results of TG-FTIR experiments showed that there was only one stage of decomposition process that happened after the subliming of leucine. The gas products were CO2, NH3, CO and some organic compounds such as 3-methyl-1-butanamine, and the main primary decomposition was decarboxylation.
J. Li, Z. Wang, X. Yang, L. Hu, Y. Liu and C. Wang, Thermochimica Acta 447 (2006) 147-153

A0495 – Thermal analysis and microscopical characterization of cholesterol in gallstones

Cholesterol constitutes the major component of most gallstones. It was identified and determined in gallstones by thermal analysis technique (DSC and TG-DTA), mainly by the use of the melting temperature (Tonset=145°C and Tmax=149°C) and by DTG peak decomposition (Tmax=364°C). Cholesterol anhydrous (ChA), which showed endothermic polymorphic peak, Tmax=40°C, without mass loss, was differentiated from cholesterol monohydrate (ChH), which showed a broad endothermic peak, Tmax=59°C, attributed to loss of water of crystallization (theoretical 4.45%). Morphological studies of gallstones were performed by optical microscopy and scanning electron microscopy (SEM). The stones consisted of a pigmented core with a variably-sized irregular central cavity, surrounded by a radially arranged deposits of plate-like ChH. The outer part of the stones showed ChA crystal arborescences. X-ray microanalysis gave a typical spectrum rich in C and O, and in some instances the presence of P, which was attributed to the presence of phospholipids. CaCO3 was easily characterized by TG with the use of DTG decomposition peak at 674°C.
J. Kaloustian , P. Lechene De La Porte, T. El-Moselhy, H. Lafont and H. Portugal, Journal of Thermal Analysis and Calorimetry 82 (2005) 331-338

A0489 – Infrared and nuclear magnetic resonnance structural studies vs thermal treatment of geopolymers / biphasic calcium phosphates

In biomaterial field, the introduction of new types of composites presents a great interest for orthopaedic surgeons. In this work, geopolymers which are a family of aluminosilicates were synthesised and mixed with biphasic mixture (hydroxyapatite and of tricalcic phosphate). The optimised thermal treatment causes the reduction of pH to 7 units and favours the expansion of composites. Consequently, the increasing of porosity percentage was induced. These properties offer a good opportunity for applied composite as potential osseous biomaterial. To study the consequences of thermal treatment in the initial amorphous structure of composites some physico-chemical techniques like SEM, MAS-NMR and FTIR were employed. These methods permitted to evaluate the porosity, different links in composites and contributions of different groups of Si and Al before and after thermal treatment.
H. Oudadesse, A.C. Derrien, M. Lefloch, Journal of Thermal Analysis and Calorimetry 82 (2005) 323-329

A0486 – Calorimetric study and thermal analysis of crystalline nicotinic acid

As one primary component of Vitamin B3, nicotinic acid [pyridine 3-carboxylic acid] was synthesized, and calorimetric study and thermal analysis for this compound were performed. The low-temperature heat capacity of nicotinic acid was measured with a precise automated adiabatic calorimeter over the temperature rang from 79 to 368 K. No thermal anomaly or phase transition was observed in this temperature range. A solid-to-solid transition at T trs=451.4 K, a solid-to-liquid transition at T fus=509.1 K and a thermal decomposition at T d=538.8 K were found through the DSC and TG-DTG techniques. The molar enthalpies of these transitions were determined to be trs H m=0.81 kJ mol-1, fus H m=27.57 kJ mol-1 and d H m=62.38 kJ mol-1, respectively, by the integrals of the peak areas of the DSC curves.
S.X. Wang, Z.C. Tan, Y.Y. Di, F. Xu, M.H. Wang, L.X. Sun, T. Zhang, Journal of Thermal Analysis and Calorimetry 76 (2004) 335-342

A0450 – Thermodynamic studies of monuron

Monuron (C9H11ClN2O; N,N-dimethyl-N'-(4-chlorophenyl) urea, CAS 150-68-5) was synthesized and the heat capacities of the compound were measured in the temperature range from 79 to 385 K with a high precision automated adiabatic calorimeter. No phase transition or thermal anomaly was observed in this range. The enthalpy and entropy data of the compound relative to the reference temperature 298.15 K were derived based on the heat capacity data. The thermodynamic properties of the compound were further investigated through DSC and TG analysis. The melting point, the molar enthalpy, and entropy of fusion were determined to be 447.6±0.1 K, 29.3±0.2 kJ mol-1, and 65.4 J K-1 mol-1, respectively.
L-G. Kong, Z.C. Tan, J-T. Mei, L-X. Sun, X-H. Bao, Thermochimica Acta 414 (2004) 131-135

A0446 – Thermodynamic study of ibuprofen by adiabatic calorimetry and thermal analysis

Molar heat capacities of ibuprofen were precisely measured with a small sample precision automated adiabatic calorimeter over the temperature range from 80 to 400 K. The polynomial functions of Cp,m (J K-1 mol-1) versus T were established on the heat capacity measurements by means of the least fitting square method. The functions are as follows: for solid ibuprofen, at the temperature range of 79.105 K=T=333.297 K, Cp,m=144.27+77.046X+3.5171X2+10.925X3+11.224X4, where X=(T-206.201)/127.096; for liquid ibuprofen, at the temperature range of 353.406 K=T=378.785 K, Cp,m=325.79+8.9696X-1.6073X2-1.5145X3, where X=(T-366.095)/12.690. A fusion transition at T=348.02 K was found from the Cp-T curve. The molar enthalpy and entropy of the fusion transition were determined to be 26.65 kJ mol-1 and 76.58 J mol-1 K-1, respectively. The thermodynamic functions on the base of the reference temperature of 298.15 K, (HT-H298.15) and (ST-S298.15), were derived. Thermal characteristic of ibuprofen was studied by thermo-gravimetric analysis (TG-DTG) and differential scanning calorimeter (DSC). The temperature of fusion, the molar enthalpy and entropy of fusion obtained by DSC were well consistent with those obtained by adiabatic calorimeter. The evaporation process of ibuprofen was investigated further by TG and DTG, and the activation energy of the evaporation process was determined to be 80.3±1.4 kJ mol-1.
F. Xu, L-X. Sun, Z-C. Tan, J-G. Liang, R-L. Li, Thermochimica Acta 412 (2004) 33-37

A0437 – The use of thermal analysis in determination of some urinary calculi of calcium oxalate

The human urinary calculi are mainly constituted by calcium oxalate, magnesium ammonium phosphate hexahydrate, and uric acid. The ions or molecules are easily characterized by wet chemical methods. The difficulties appear in the differentiation of the hydrates of calcium oxalate (monohydrate COM or Whewellite, and dihydrate COD or Weddelite). A high level of COD in the urinary stones leads, often, inflammation, sharp pain and blood in urine. In the worse cases, they must be extracted by surgical way.
J. Kaloustian, A.M. Pauli, G. Pieroni, H .Portugal, Journal of Thermal Analysis and Calorimetry 70 (2002) 959-973

A0312 – Identification par analyse thermique de quelques excipients pharmaceutiques

J. Kaloustian, A.M. Pauli, J. Pastor, JEEP (1995) 248-251