Improved solubility, dissolution, and oral bioavailability for atorvastatin-Pluronic® solid dispersions.

Abstract

Despite the status of atorvastatin (AT) as one of the top selling statins for prophylaxis against primary and secondary cardiovascular diseases, its limited oral absorption limits its full therapeutic benefits. Herein, formulations of AT with amphiphilic carriers (Pluronic F127® and Pluronic F68®) were developed in the form of hard capsules to improve in vitro solubility and dissolution, as well as in vivo oral bioavailability. Prepared formulas were characterized by assessing solubility improvements in the carrier solution and examining the FTIR, DSC, and X-RPD profiles for each formula. The dissolution rate and absorption were also examined after oral administration to New Zealand rabbits. The solubility of AT was improved by the incorporation of either Pluronic F127® or Pluronic F68®. No chemical changes or interactions were detected using X-RPD, DSC, and FTIR characterization. Dissolution profiles revealed an increase in the rate and maximum amount of dissolved AT and showed that up to 93% of the AT content was dissolved within 30min. In vivo absorption of the tested formula (Cmax=1146ng/ml and AUC0-12 to 9,993.4ng.h/ml) was greater than Lipitor® (Cmax=642.3ng/ml and AUC0-12=4427.4ng.h/ml) and AT (Cmax=517.6ng/ml and AUC0- 12=2,473.7ng.h/ml). In conclusion, the formulation of AT with Pluronics® profoundly augments the dissolution behavior and absorption of AT and may serve as a useful approach for improving AT therapeutic and clinical efficacy.