Development and Optimization of Sustained Release Atorvastatin-Loaded Polymeric Nanoparticles using Quality by Design (QbD) Approach

Atorvastatin is a popular statin medication, classified as a BCS class-II medication, which has poor aqueous solubility and immediate release, and lower bioavailability, altering its medical efficacy with potential side effects. To overcome these challenges, the current study utilized the Quality-based design (QbD) approach to optimize atorvastatin calcium (AVC) nanoparticles via central composite design of Design Expert® software. Independent variables inputs were Eudragit S100 (100-500mg) as pH-sensitive polymer and PVA (1-5ml) as stabilizer, while the analyzed responses were particle size (nm), drug loading (%), and percentage drug release (%). Initially, the pre-formulation studies confirmed the compatibility of AVC with the polymer. ANOVA analysis in response surface graphs depicted a higher F-value and an insignificant lack of fit (p-value) for all dependent variables, confirming the significance of the model. Out of the 13 formulations suggested by the software, the formulation containing 354.28mg of Eudragit S100 and 3.79ml of PVA was selected as the best optimized formulation for nanoparticle development with a 0.726 desirability value. The optimized nanoparticles exhibited 385.6nm particle size, 86.2% entrapment efficiency, and 83.4% drug release. The optimized AVC nanoparticle also revealed a 0.235 poly-dispersibility index (PDI), 42.7mV zeta potential, and sustained release pattern for intestinal targeting. This approach helps in establishing a statistically validated formulation process by overcoming the limitations, which signifies the potential for targeted and controlled drug delivery applications.