Enhancement of the Solubility of Rosuvastatin Calcium by Nanovesicular Formulation: a Systematic Study Based on Quality by Design Approach

Abstract

Rosuvastatin calcium (Rsv) is an effective statin, with a potent antihyperlipidemic effect. However, it suffers poor bioavailability owing to its poor solubility. Thus; encapsulating Rsv into a nanovesicular structure could overcome this problem. The aim of this work is to investigate the potential of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in enhancing the solubility of Rsv, using Quality by Design (QbD) concept. A complete risk assessment study has been conducted, where the critical process parameters (CPP), material attributes (MA), and critical quality attributes have been identified using the ishikawa diagrams. Selected CPP/MA were screened and further upgraded to a 24 full factorial design to develop the design space with the optimized formula. The screened CPP/MA were tested on each of the particle size, polydispersity index (PDI), zeta potential (ζ-pot) and the entrapment efficiency (EE%). A comprehensive approach for Rsv nanovesicular carriers has been conducted, where the NLC showed better results than the SLN. The optimized formula was prepared with 3% total lipid content, 0.154% surfactant, and 9.4 mg drug. The optimized formula had a particle size of 310.5 nm, with 0.243 PDI, a ζ-pot of −24.7 mV and EE% of 93.87%, and showed a sustained release of the drug up to 72 h. It successfully lowered each of the total cholesterol, low density lipoprotein, and triglycerides and elevated the level of the high density lipoprotein of the rats, with better results as compared to the standard drug. Thus, a complete QbD study was conducted to explore experimental regions for many successful nanovesicular carriers for the enhancement of the solubility of poorly soluble drugs.