Microemulsion-Mediated Abiraterone Acetate Nanoparticles: Formulation and Optimization

Abstract

The BCS Class IV drug abiraterone acetate (ABR) exhibits biopharmaceutical difficulties including polymorphism, poor solubility (< 0.5 µg/mL), variable permeability, and low oral bioavailability (<10 %, necessitating a large dose of 1000 mg/day). The primary goal of the current study is to produce solid lipid nanoparticles (SLNs) that are loaded with ABR to improve solubility. SLNs were manufactured by O/W microemulsion method. Initial screening of lipids was done by solubility study whereas surfactants and co-surfactants were selected on the basis of their HLB values. Based on preformulation studies, Myristic acid, Tween 80 and PEG 400 were selected for SLN composition. Using Central Composite Design (CCD) experiments were conducted to optimize the composition using concentration of solid lipid and S-mix as independent variables while particle size, entrapment efficiency (EE), and zeta potential as independent variables. Optimized SLN formulation and pure drug were compared for in vitro drug release. Cytotoxicity study of optimized formulation was tested using MTT assay method. The statistical evaluation confirmed that optimized ABR-SLNs were spherical with average size of 194.26 nm, polydispersity index (PDI) of 0.491, EE of 89.56 %, and zeta potential of -23.77 mV. Drug release from optimized formulation over 6 h and cytotoxicity study demonstrated remarkable anticancer activity. It was observed that SLN shows significant improvement in the solubility of ABR. Hence, SLN can acts as drug delivery system for enhancing the solubility of poorly soluble drugs.