THERMAL-ANALYSIS OF CHIRAL DRUG MIXTURES - THE DSC BEHAVIOR OF MIXTURES OF EPHEDRINE HCL AND PSEUDOEPHEDRINE HCL ENANTIOMERS

A method for peak shape analysis and deconvolution of overlapping endo therms in differential scanning calorimetry (DSC) data has been previo usly reported. In this study the method is applied to binary mixtures of, (i) (1S,2S)-(+)- and (1R,2R)-(-)-PSI-ephedrine HCl, and (ii) (1S,2 S)-(+)-PSI-ephedrine HCl and its diastereomer, (1S,2R)-(+)-ephedrine H Cl. Phase diagrams based on enthalpies of fusion at the melting point (DELTAH(f)m) as a function of mol% composition are linear. However, th e phase diagrams based on melting temperature as a function of mol% co mposition are non-linear and show deviations from the theoretical Prig ogine-Defay and Schroder-van Laar equations. Estimates of eutectic com positions are more definitive from the diagrams based on DELTAH(f)m va lues. The phase diagram for the PSI-ephedrine HCl enantiomers demonstr ates racemic compound formation with eutectic points for the compound and the pure enantiomers at 28.1 +/- 2.5 mol% and 71.9 +/- 2.5 mol%. T he DELTAH(f)m phase diagram for mixtures of (1S,2R)-(+)-ephedrine HCl and (1S,2S)-(+)-PSI-ephedrine HCl suggested the formation of a weak co mplex with a composition close to 60 mol% of the (1S,2S)-(+)-isomer.