APPLICATIONS OF PRESSURE DIFFERENTIAL SCANNING CALORIMETRY IN THE STUDY OF PHARMACEUTICAL HYDRATES .1. CARBAMAZEPINE DIHYDRATE

The dehydration of carbamazepine dihydrate (C15H12N2O . 2H(2)O) was st udied by both conventional differential scanning calorimetry (DSC) and by pressure differential scanning calorimetry. Variable temperature p owder X-ray diffractometry (VTXRD) and thermogravimetric analysis were used as complementary techniques. By performing DSC at elevated press ures, the dehydration and vaporization endotherms were separated and i t was possible to determine the enthalpy of dehydration. Over the rang e of 100-600 psi, the enthalpy of dehydration was unaffected by pressu re. However, the solid-state of the anhydrous phase formed was influen ced by the DSC conditions. At ambient pressure, dehydration resulted i n the formation of the gamma-form of anhydrous carbamazepine while at elevated pressures, the anhydrous beta-form appeared which converted t o the gamma-form at higher temperatures. At high pressures, the water liberated on dehydration is not immediately removed and its presence a ppears to be responsible for the formation of beta-carbamazepine. VTXR D permitted in situ study of dehydration and this confirmed the DSC re sults. A specially fabricated sample holder permitted VTXRD studies at elevated pressures. (C) 1997 Elsevier Science B.V.