Vapor pressure and heat of sublimation of crystal polymorphs

In order to determine the applicability of vapor pressure studies on polymo rphic modifications, pairs of enantiotropically related modifications of ca ffeine, theophylline and carbamazepine were investigated. The studies were performed over a wide temperature range (71 to 191 degrees C) and according ly over a wide vapor pressure range (0.02 to 400 Pa) using an automatic ins trument constructed on the basis of the gas saturation principle. This inst rument enables an analytical determination of the main component and the im purities present by the chromatographic separation of the substances transp orted in the gas flow. Therefore, the real partial pressure of the main com ponent can be measured. Due to the high precision of the applied method it was possible to determine partial pressure curves and the thermodynamic tra nsition temperature - the point at which the vapor pressure of two crystal polymorphs is equal. The thermodynamic transition temperatures of caffeine and theophylline were determined to be 136 and 232 degrees C, respectively. These values are in agreement with experimental or calculated values deriv ed from DSC investigations but are more reliable. Vapor pressure measuremen ts of carbamazepine are only meaningful in the low temperature range due to its decomposition at high temperatures. The thermodynamics, advantages and limits of vapor pressure determinations of polymorphic modifications are d iscussed.