Properties of the racemic species of verapamil hydrochloride and gallopamil hydrochloride

It is well known that the stereoselective actions associated with the enantiomeric constituents of a racemic drug candiffer markedly in their pharmacodynamic or pharmacokinetic properties. Nevertheless, molecular chirality manifestsitself in the solid, that is, crystalline state. The aim of this work was to characterize the solid-state properties ofverapamil HCl and gallopamil HCl, two well-known chiral calcium channel antagonists. The characterization of thesolid state for the single enantiomers and equimolecular mixtures for both the calcium antagonists was performed bysolid-state techniques such as Fourier transform infrared (FT-IR spectroscopy), X-ray powder diffractometry (XRD)and differential scanning calorimetry (DSC). The FT-IR spectra and XRD of the single enantiomers are differentfrom those of the corresponding equimolecular mixture owing to their different crystalline structure. The thermalbehavior of the racemates and pure enantiomers were examined by DSC, and the resultant experimental andtheoretical binary phase diagrams are discussed. Spectroscopic solid-state techniques, such as FT-IR and XRD, areuseful in combination with thermal analysis for characterizing the racemic species of chiral drugs. The data obtainedprove that the equimolecular mixtures of both verapamil hydrochloride and gallopamil hydrochloride exist as racemiccompounds. Determination of the enantiomeric purity of the enantiomers and racemic compounds of both thecalcium antagonists analyzed was performed by DSC.