Properties of the racemic species of verapamil hydrochloride and gallopamil hydrochloride

• Published in: International journal of pharmaceutics 1999-02, Vol.178 (1), p.111-120
• Main Authors: Rustichelli, Cecilia, Gamberini, M.Cristina, Ferioli, Valeria, Gamberini, Gianfranco
• Format: Article
• Language: English
• Subjects: Analysis; Biological and medical sciences; Calcium Channel Blockers - chemistry; Chemistry Techniques, Analytical; Chirality; Chromatography, High Pressure Liquid; Crystallization; Differential scanning calorimetry; FT-IR spectrometry; Gallopamil - chemistry; Gallopamil hydrochloride; General pharmacology; Medical sciences; Pharmacology. Drug treatments; Phase diagram; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Stereoisomerism; Structure-Activity Relationship; Temperature; Verapamil - chemistry; Verapamil hydrochloride; X-Ray Diffraction; X-ray powder diffraction
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(98)00355-X

It is well known that the stereoselective actions associated with the enantiomeric constituents of a racemic drug can differ markedly in their pharmacodynamic or pharmacokinetic properties. Nevertheless, molecular chirality manifests itself in the solid, that is, crystalline state. The aim of this work was to characterize the solid-state properties of verapamil HCl and gallopamil HCl, two well-known chiral calcium channel antagonists. The characterization of the solid state for the single enantiomers and equimolecular mixtures for both the calcium antagonists was performed by solid-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 different from those of the corresponding equimolecular mixture owing to their different crystalline structure. The thermal behavior of the racemates and pure enantiomers were examined 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 characterizing the racemic species of chiral drugs. The data obtained prove that the equimolecular mixtures of both verapamil hydrochloride and gallopamil hydrochloride exist as racemic compounds. Determination of the enantiomeric purity of the enantiomers and racemic compounds of both the calcium antagonists analyzed was performed by DSC.