Chemometric approach for developing nanostructured self-emulsifying drug delivery systems of rosuvastatin calcium containing a dietary lipid with improved biopharmaceutical performance

摘要

Objective(s): The present work deals with the development of nanostructured self-emulsifying delivery system of rosuvastatin calcium containing a dietary lipid by chemometry principles for improving the biopharmaceutical performance of the drug. Excipient screening was performed on the basis of solubility of drug and phase behaviour study using aqueous titration method. A blend of liquid lipids, emulgents and coemulgents were used as for preparing the self-emulsifying delivery systems of the drug. Methods: Optimal mixture design was adopted for systematic optimization of the composition of self-emulsifying formulations and evaluated for emulsification time, globule size, polydispersity index, zeta potential and in vitro drug release. In vitro drug release in simulated fluids, and in vivo pharmacokinetic in rats was performed for comparing the biopharmaceutical performance. Results: The optimized self-nanoemulsifying formulation contained 15% of lipid (isopropyl myristate), 75% of emulgent (Tween 20) and 10% of cosolvent (ethanol), which exhibited fast emulsification in 150 second, globule size of 68 nm, zeta potential of 27 mV and more than 85% drug release within 30 minutes. Conclusions: Pharmacokinetic study in rats indicated 4.89 to 4.45-folds improvement in the values of AUC and Cmax, and 0.95-folds reduction in Tmax from the self-nanoemulsifying system vis-à-vis the pure drug. Overall, the developed nanolipidic formulation of rosuvastatin indicated superior efficacy in augmenting the drug dissolution and absorption performance.