Solid-state properties of drugs. III. Differential scanning calorimetry of chiral drug mixtures existing as racemic solid solutions, racemic mixtures or racemic compounds

Abstract

A previously reported method for peak shape analysis and deconvolution of overlapping endotherms in differential scanning calorimetry (DSC) data has been applied to binary mixtures of the enantiomers of a chiral drug and of two model compounds. The chiral substances represented the three types of known phase behavior for chiral compounds, i.e., racemic solid solutions (camphorquinone), racemic mixtures (propranolol hydrochloride) and racemic compounds (mandelic acid). Phase diagrams based on enthalpies of fusion ( ΔH f m) for camphorquinone and propranolol hydrochloride were as easy to interpret as those based on melting behavior. However, the phase diagram based on ΔH f m for mandelic acid was much easier to interpret than the melting behavior phase diagram. Formation of the racemic compound of mandelic acid by thorough grinding of mixtures of the enantiomers was demonstrated by DSC and infrared spectra. A novel, fast method of chiral purity determination is suggested for propranolol hydrochloride. The DSC endotherm peak asymmetry was shown to be a linear function of enantiomeric composition in the range 85–100 mol%. This approach may also be applicable to chiral mixtures of other drugs.