THERMODYNAMIC STUDY OF SULFANILAMIDE POLYMORPHISM .1. MONOTROPY OF THE ALPHA-VARIETY

Purpose. Sulfanilamide was chosen as a model compound in order to gain insights on the stability hierarchy of drug polymorphs from structura l and thermodynamic criteria. Despite numerous studies, disagreements remained on the reported enthalpies associated with the mutual interco nvertions of the alpha-, beta-, and gamma-forms of sulfanilamide. Ther efore, the unambiguous determination of these enthalpies was the purpo se of this work. Methods. Samples, free of solvent inclusions and made of only one form, were prepared, and analyzed combining X-ray powder diffraction and Differential Scanning Calorimetry (DSC). Results. The enthalpy values associated with the alpha- to gamma- and beta- to gamm a-transitions were found to be + 10.2 and + 10.9 J g(-1), respectively . The calculated enthalpy of the beta- to alpha-transition is consiste nt with the experimental one (+ 1 J g(-1)). Conclusions. The monotropy of the alpha-form was ascertained over the explored temperature range at ordinary pressure.