Solubility enhancement and IVIVC analysis of an optimized rosuvastatin calcium-2-hydroxypropyl-β-cyclodextrin inclusion complex: a comprehensive study

Rosuvastatin calcium (RS), a BCS class II drug, widely prescribed for the prevention of hyperlipidemia and cardiovascular disease, faces significant bioavailability challenges due to its low solubility and poor dissolution profile. This study sought to enhance the oral bioavailability of RS through the formulation of an inclusion complex with 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD). The phase solubility study confirmed a 1:1 inclusion complex with a stability constant (Kc) of 202.89 ± 0.31 M⁻¹. Optimization using factorial design identified the optimal conditions as, kneading time of 60 min and a drug-polymer ratio of 1:1. Characterization techniques confirmed the successful complexation of RS-HP-β-CD with a high drug content of 99.867 ± 1.107 mg. The solubility analysis showed a two- to six-fold increase in solubility in all tested media (simulated-gastric-fluid (SGF); simulated-intestinal-fluid (SIF); and distilled water). In vitro dissolution studies demonstrated accelerated drug release from the RS-HP-β-CD complex in all tested media compared with the pure RS. Pharmacokinetic studies in Sprague-Dawley rats revealed a three-fold increase in relative bioavailability, with faster T_max (1.0 ± 0.237 h), higher C_max (254.735 ± 0.877 ng/mL), and absolute bioavailability of 83.32 ± 1.05% for the inclusion complex. A robust Level A IVIVC (R² = 0.869) confirmed the correlation between the in vitro dissolution and in vivo absorption profiles. Accelerated stability studies demonstrated the robustness of the complex, preserving 99.201 ± 0.378% of the drug content while maintaining consistent solubility and dissolution characteristics. These results highlight the potential of RS-HP-β-CD complexes to enhance therapeutic effectiveness and offer a viable strategy for overcoming the solubility and bioavailability limitations of poorly soluble drugs.