AN388 – Determination of crystalline.amorphous phase-zh

DETERMINATION OF CRYSTALLINE, AMORPHOUS PHASE

REFERENCE

SANOFI SYNTHELABO, Analytical Department, Toulouse, FRANCE

AN-388

EXPERIMENTAL

  • Study of a drug (Irbesartan) having two polymorphous phases A and B. Two samples under powder form.
  • The operation is run in three steps :
  • The sample is heated up to 150°C and a 400V/mm high field is applied
  • 2. The sample is “quenched” at a cooling rate of 20°C/min and the field is removed when a temperature of -150°C is reached.
  • 3. The sample depolarization current is recorded from –150°C to +150°C with a heating rate 7°C/min.

RESULTS

Peak observed between 100°C and 150°C (αc) correspond to the molecular mobility associated with the dielectric expression of the melting of two polymorphous phases A and B. Melting observed with DSC too. Molecular mobility at low temperature (bA, gA) specific to form A. Event NOT observed with DSC.
The events at low temperature, from -150°C to -50°C, were attributed to molecular mobility located in the channels, typical of the structure of Irbesartan, form A. They were absent in form B and in the amorphous phase.

DETERMINATION OF CRYSTALLINE, AMORPHOUS PHASE

REFERENCE

SANOFI SYNTHELABO, Analytical Department, Toulouse, FRANCE

AN-388a

EXPERIMENTAL

  • DSC measurements were run with 100% crystalline samples of A and B.
  • Thermograms recorded with heating rate of 10°C/min from 25 to 210°C under a dry nitrogen.

RESULTS

Only one event observed. An endothermic peak characteristic of the melting of the crystalline forms.

Form A: 181°C
Form B: 186°C is the more stable

No solid-to-solid transition is not expected between the two forms. No amorphous content detected.

DETERMINATION OF CRYSTALLINE, AMORPHOUS PHASE

AN-388b

REFERENCE

SANOFI SYNTHELABO, Analytical Department, Toulouse, FRANCE

EXPERIMENTAL

We wish to establish a calibration curve allowing the determination of the crystalline phase in a unknown mixture. We study the event in the low temperature range (-150°C to -50°C). It is linked with the molecular mobility located in the channels, typical of the structure of Irbesartan, form A. Study was carried out of physical crystal mixtures of form A / amorphous, prepared in a range from 100 to 0%.

RESULTS

Rates of crystallinity as low as 2.5% can be detected. After normalization, evaluation of percentage of crystallinity from the TSC consistent with that given by the chemical composition of the mixtures.