Solid-state properties of drugs. II. Peak shape analysis and deconvolution of overlapping endotherms in differential scanning calorimetry of chiral mixtures

Abstract

A method for peak shape analysis and deconvolution of overlapping endotherms in differential scanning calorimetry (DSC) data is presented. The method employed a commercial computer program (PeakFit ®), which fits the experimental data to two (or more) overlapping distribution functions in which heat flux is the dependent variable and temperature is the independent variable. The endotherms were found to have either Gaussian or exponentially modified Gaussian distributions. In the examples given here, a very pure reference material, benzoic acid, and a slightly impure (99.9%) sample of (±)-ephedrine hydrochloride gave single Gaussian peak shapes, whereas a slightly impure (99.9%) sample of (1 R,2 S)-(−)-ephedrine hydrochloride displayed a single exponentially modified Gaussian peak. Binary mixtures of (1 S,2 R)-(+)- and (1 R,2 S)-(−)-ephedrine hydrochloride gave two overlapping peaks, both of which had exponentially modified Gaussian distributions. Deconvolution of these overlapping peaks allowed construction of a solid-liquid phase diagram based on their enthalpies of fusion. This phase diagram consisted of linear plots which are easily interpolated or extrapolated. Detection of one isomer in the presence of a large excess of the other by DSC was possible for compositions containing 1.5 mol% of the minor component.