Improved Bioavailability of Spironolactone–Hydroxypropyl-β-Cyclodextrin Complex Tablets Evaluated in Rat Model

Abstract Purpose Spironolactone (SPL) is a mineralocorticoid receptor antagonist widely used in the management of hypertension and heart failure; however, its poor aqueous solubility and variable oral bioavailability limit its therapeutic performance. This study aimed not only to enhance the solubility and dissolution behavior of SPL through Hp-βCD complexation, but also to translate this approach into a scalable tablet dosage form and evaluate its in vitro and in vivo performance. Methods An Hp-βCD: SPL inclusion complex (1:1 molar ratio) was prepared using the kneading method. The solid-state characteristics and complex formation were evaluated by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Solubility studies were conducted in acidic medium (0.1 N HCl, pH 1.2, 0.1% SLS). Tablets containing either pure SPL or the Hp-βCD: SPL complex were manufactured by direct compression and evaluated for flow properties, mechanical strength, and disintegration. In vitro dissolution testing and in vivo pharmacokinetic studies in rats were performed to assess drug release and oral bioavailability. Results Spectroscopic and thermal analyses confirmed successful inclusion complex formation and transformation of SPL from a crystalline to an amorphous state. The Hp-βCD: SPL complex exhibited approximately a 6–7-fold increase in SPL solubility compared to pure drug. Dissolution studies demonstrated markedly enhanced drug release from Hp-βCD: SPL tablets, achieving 75% release within 10 min and 95% within 30 min, compared with 35% and 76%, respectively, for conventional SPL tablets. Pharmacokinetic evaluation revealed significantly higher plasma SPL concentrations, increased C_max, and elevated AUC₀–∞ values for Hp-βCD: SPL tablets, indicating improved absorption and relative bioavailability. Conclusion Inclusion complexation of spironolactone with Hp-βCD represents a simple yet effective formulation innovation to overcome solubility- and dissolution-related limitations of SPL. The developed Hp-βCD: SPL tablet formulation significantly improves oral bioavailability and offers a promising approach for achieving more consistent therapeutic outcomes in BCS Class II drugs. Graphical Abstract Hp-βCD inclusion complexation transforms crystalline spironolactone into an amorphous form, enhancing dissolution and oral bioavailability