RESUMO
In the present work, an attempt was undertaken to improve the oral bioavailability and anticancer activity of abiraterone acetate. Solid lipid nanoparticles (SLNs) were developed using the quality by design (QbD) principles and evaluated through in vitro, ex vivo, and in vivo studies. Solid lipid suitability was evaluated by equilibrium solubility study, while surfactant and cosurfactant were screened based on the ability to form microemulsion with the selected lipid. SLNs were prepared by emulsion/solvent evaporation method using glyceryl monostearate, Tween 80, and Poloxamer 407 as the solid lipid, surfactant, and cosurfactant, respectively. Box-Behnken design was applied for optimization of material attributes and evaluating their impact on particle size, polydispersity index, zeta potential, and entrapment efficiency of the SLNs. In vitro drug release study was evaluated in simulated gastric and intestinal fluids. Cell culture studies on PC-3 cells were performed to evaluate the cytotoxicity of the drug-loaded SLNs in comparison to the free drug suspension. Qualitative uptake was evaluated for Rhodamine B-loaded SLNs and compared with free dye solution. Ex vivo permeability was evaluated on Wistar rat intestine and in vivo pharmacokinetic evaluation on Wistar rats for SLNs and free drug suspension. Concisely, the SLNs showed potential for significant improvement in the biopharmaceutical performance of the selected drug candidate over the existing formulations of abiraterone acetate.
RESUMO
The present study described the development of a reversed-phase liquid chromatographic method for the estimation of abiraterone acetate by Quality by Design (QbD) approach. Using an isocratic solvent system for the mobile phase, the chromatographic estimation of analyte was performed on a Hypersil BDS C18 column using mobile phase mixture containing acetonitrile and water with pH adjusted with 0.1% v/v orthophosphoric acid (15:85%v/v ratio), flow rate 1.0 mL.min-1 and detection at 250 nm using photodiode array detector. Systematic development of the chromatographic method was carried out by factor screening using a half-factorial design which suggested organic modifier (%), flow rate (mL.min-1) and autosampler temperature (°C) as influential variables. Further, the method was optimized by Box-Behnken design and trials performed were evaluated for the area under peak, retention time, theoretical plate count and tailing factor as the responses. Validation of the developed method showed good linearity, accuracy, precision and sensitivity. Evaluation of the stability-indicating profile of the method using forced degradation studies revealed the formation of a possible degradation product under acidic and alkaline conditions, while no such degradation product peaks were observed under the oxidative environment. Overall, the study construed the successful development of HPLC assay method for pharmaceutical applications.
