Properties of the racemic species of verapamil hydrochloride and gallopamil hydrochloride

It is well known that the stereoselective actions associated with the enant iomeric constituents of a racemic drug can differ markedly in their pharmac odynamic or pharmacokinetic properties. Nevertheless, molecular chirality m anifests itself in the solid, that is, crystalline state. The aim of this w ork was to characterize the solid-state properties of verapamil HCl and gal lopamil HCl, two well-known chiral calcium channel antagonists. The charact erization of the solid state for the single enantiomers and equimolecular m ixtures for both the calcium antagonists was performed by solid-state techn iques such as Fourier transform infrared (FT-IR spectroscopy), X-ray powder diffractometry (RD) and differential scanning calorimetry (DSC). The FT-IR spectra and XRD of the single enantiomers are different from those of the corresponding equimolecular mixture owing to their different crystalline st ructure. The thermal behavior of the racemates and pure enantiomers were ex amined by DSC: and the resultant experimental and theoretical binary phase diagrams are discussed. Spectroscopic solid-state techniques, such as FT-IR and XRD, are useful in combination with thermal analysis for characterizin g the racemic species of chiral drugs. The data obtained prove that the equ imolecular mixtures of both verapamil hydrochloride and gallopamil hydrochl oride exist as racemic compounds. Determination of the enantiomeric purity of the enantiomers and racemic compounds of both the calcium antagonists an alyzed was performed by DSC. (C) 1999 Elsevier Science B.V. All rights rese rved.