Acta Pharm. 49 (1999) 79-88

Isothermal interconversion of chlorpropamide polymorphs kinetically quantified by
X-ray powder diffractometry, diffuse reflectance Fourier transform
infrared spectroscopy and isoperibol solution calorimetry

MELGARDT M. DE VILLIERS^*1  and   DALE ERIC WURSTER ²

¹Research Institute for Industrial Pharmacy, Potchefstroom University for CHE, Potchefstroom 2520, South Africa
²College of Pharmacy, University of Iowa,  Iowa City,  IA 52242, USA

The effect of temperature on the stability of polymorphs is important because it can influence the performance of chlorpropamide tablets. In this study the thermal conversion of chlorpropamide polymorphs A and B, to form C, the most soluble form, were followed using X-ray powder diffractometry (XRD), diffuse reflectance Fourier-transform infrared spectroscopy (DRIFTS) and isoperibol solution calorimetry. By determining the Prout-Tompkins kinetics of the conversions of forms A and B to C, the thermal stabilities of the polymorphic forms were determined. The conversion of form B to C was much faster than the conversion of form A to C. The rate of conversion to form C for both form A and B increased with an increase in temperature. However, although form A changed directly to form C, form B changed to an intermediate before completely converting to form C. XRD and DRIFTS suggested that this intermediate might be form A. Heat of solution change for the conversion of form A to C agreed with predicted value and confirmed the complex transformation of form B to form C.

Keywords: chlorpropamide, polymorph, transformation, temperature, calorimetry