In vitro Analysis of the Pharmaceutical Interactions between Verapamil Hydrochloride and Citric Acid

Abstract

The objective of this study is to investigate the combination of drug-drug interactions involving different functional groups by assessing the interaction of a BCS class IV compound (Verapamil Hydrochloride) with Citric acid in various ratios, thereby enhancing the understanding of pharmacological implications. This study elucidated the compatibility between Verapamil Hydrochloride (HCl) and Citric acid, demonstrating an approach to enhance the solubility, permeability, and bioavailability of poorly water-soluble drugs in pharmaceutical applications. The method of solvent evaporation was utilized for the preparation of solid dispersions. This process involved dissolving the active pharmaceutical ingredient and citric acid in ethanol, evaporating the solvent to yield a solvent-free film, and mechanically reducing the residue using a mortar and pestle. The resultant fine powder was sieved through a 40-mesh filter and appropriately stored in vials for subsequent analyses. FT-IR spectra and an HPLC-sensitive method were employed to evaluate the solubility profile and interaction dynamics of the compound. FT-IR spectra of VPM HCl and its physical mixtures with citric acid at ratios of 1:3, 1:5, and 1:7 were obtained using an FT-IR spectrophotometer. The spectra revealed structural and functional group alterations, quantified by analyzing the magnitude and cumulative area of the peaks corresponding to the structural constituents. In accordance with the established linearity, the retention times for VPM HCl, Sample 1, Sample 2, and Sample 3 were recorded as 6.8 ± 0.2, 2.7 ± 0.1, 5.5 ± 0.2, and 3.8 ± 0.1 minutes, respectively, across a concentration range of 1–100 µg/mL. For all analytes, the intra-assay and inter-assay biases were observed to be within 15% and 13.4%, respectively. Furthermore, In vitro evaluations of physical combinations of Verapamil HCl and Citric acid samples revealed minimal interaction. These findings emphasize the stability and compatibility of Verapamil HCl and citric acid, demonstrating citric acid’s role as a reliable excipient for enhancing drug solubility and bioavailability without compromising therapeutic integrity.