Amelioration of Dissolution Properties of Abiraterone Acetate via Nano-Sizing Employing High-Speed Homogenization Technique: An Optimization Study

Abstract:

Background: Abiraterone acetate is an anticancer molecule indicated for prostate cancer. The purpose of this study was to develop a nanosuspension of abiraterone acetate in order to improve its solubility, dissolution properties and bioavailability. Materials and Methods: High speed homogenization method was utilized to formulate the nanosuspension. Design of experiment (DoE) was employed for the optimization of process and formulation variables. Nanosuspension was evaluated for particle size, PDI, zeta potential, and in vitro drug release studies. Results: Preliminary studies suggested amount of stabilizer and milling time as critical variables to be taken for the optimization process. Regression analysis suggested influence of independent variables on responses. Optimized batch obtained from desirability function yielded 140.25 nm of particle size and 0.09 of PDI values. Characterization studies i.e. Differential Scanning Calorimetry and X-Ray Diffraction studies illustrated decrease in crystallinity of drug which might be thereby responsible for the dissolution enhancement of drug. The drug and formulation were found to be stable over a 6-months period in accelerated stability testing. Conclusion: Using high speed homogenization method, particle size of the formulation was reduced to nano-size which was further responsible for the improvement in dissolution and bioavailability of drug.

Keywords: Abiraterone acetate, Nanosuspension, Nanocrystals, Dissolution enhancement, Quality by Design.