Ion‐Pairing With Glycine Enhances Solubility, Dissolution, and Pharmacokinetics of Amlodipine Besylate: Physicochemical Characterization and In Vivo Evaluation

Poor aqueous solubility and variable oral bioavailability limit the therapeutic performance of amlodipine besylate. This study aimed to enhance its physicochemical and pharmacokinetic properties via ion‐pairing with glycine and evaluate its effects on solubility, dissolution, and in vivo performance. The ion‐pair complex was prepared by solvent evaporation under alkaline conditions. Characterization was performed using melting point, FTIR, and DSC analyses. Solubility was assessed at pH 1.2 and 7.4. Partition coefficient (log P ) was determined using an n ‐octanol/water system. Comparative dissolution studies were conducted, and pharmacokinetics were evaluated in Wistar rats. Acute toxicity was assessed as per OECD guideline 423. The complex showed significantly enhanced solubility (1.9‐fold at pH 1.2 and 3.1‐fold at pH 7.4; p < 0.05). DSC and FTIR confirmed molecular interaction and reduced crystallinity. Dissolution improved, with ∼1.7‐fold faster early release. A slight decrease in log P indicated increased hydrophilicity without compromising permeability. C max and AUC increased, while T max remained unchanged (p > 0.05). LD50 increased, indicating improved safety. Ion‐pairing with glycine improves solubility, dissolution, and bioavailability of amlodipine besylate without compromising permeability or safety, offering a simple and scalable strategy for poorly soluble drugs.