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

Objective(s): The present work deals with the formulation of a nanostructured self-emulsifying delivery system of rosuvastatin calcium-containing a dietary lipid by chemometric principles to improve the biopharmaceutical performance of the drug. Excipient screening was performed based on the solubility of drug and phase behavior study using an aqueous titration method. A blend of liquid lipids, emulgents, and co-emulgents used to prepare the self-emulsifying delivery systems of the drug. Methods: Systematic optimization of the composition of the different formulation of nanostructured self-emulsifying drug delivery system (NSEDDS) performed using optimal experimental study design and characterized for emulsification time, zeta potential, globule size, polydispersity index, and drug release. In vitro drug release in simulated fluids and in vivo pharmacokinetics in rats were performed to compare the biopharmaceutical performance. Results: The optimized NSEDDS contained 15% of lipid (Isopropyl myristate), 75% of emulgent (Tween 20) and 10% of co-solvent (Ethanol), which exhibited fast emulsification in 150 seconds, globule size of 68 nm, zeta potential of 27 mV and more than > 85% drug release within 30 minutes. Conclusions: In vivo pharmacokinetic study in the rat model suggested that improvement of AUC and Cmax values of 4.89 to 4.45-folds, whereas reduction of Tmax value of 0.95-folds in case of NSEDDS than pure drug. Finally, the optimized nanostructured self-emulsifying formulation of rosuvastatin calcium showed greater effectiveness in enhancing the dissolution and absorption performance of the selected model drug.