Abstract
Atorvastatin calcium (ATC), a widely prescribed lipid-lowering agent belonging to BCS Class II, exhibits low oral bioavailability (~12%) due to poor aqueous solubility and extensive hepatic first-pass metabolism. This study aimed to design, optimize, and evaluate a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of ATC. Solubility studies were conducted to screen oils, surfactants, and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the microemulsification region. An optimized formulation consisting of Capryol 90 (oil), Tween 80 (surfactant), and Transcutol HP (co-surfactant) in a 15:55:30 % w/w ratio was developed. The optimized ATC-SMEDDS exhibited a rapid self-emulsification time of 28 ± 2 seconds, an average droplet size of 32.4 ± 1.8 nm, and a zeta potential of -18.6 ± 1.2 mV. In vitro drug release studies demonstrated a significantly faster and higher cumulative drug release (98.4 ± 1.5% in 15 min) compared to the pure drug suspension (24.2 ± 2.1%). In vivo pharmacokinetic studies in male Wistar rats revealed a 3.8-fold increase in the relative oral bioavailability (AUC0-t) of the ATC-SMEDDS compared to the suspension. These findings demonstrate that the developed SMEDDS formulation is a highly promising approach to overcome solubility limitations and improve the therapeutic efficacy of atorvastatin calcium.
