Development and Optimization of Enzalutamide Nanosuspension by Design of Experiments for Dissolution Enhancement

Enzalutamide is an anticancer molecule used for prostate cancer. The goal of the study was to develop a nanosuspension of enzalutamide in order to improve its solubility and dissolution properties. High-speed homogenization method was employed to formulate the nanosuspension. Preliminary studies suggested the amount of stabilizer, homogenization time and homogenization speed as critical variables to be taken for the optimization process. Box-Behnken design was employed for the optimization of process and formulation variables. Nanosuspension was evaluated for particle size, PDI, zeta potential, and in-vitro drug release at 10 minutes (D10) studies. Regression analysis suggested the influence of independent variables on the responses. The optimized batch obtained from the overlay plot exhibited 198.36 nm of particle size, (-33.27 mV of zeta potential and 80.47% of D10 values). The characterization studies i.e., DSC, and XRD illustrated retention in crystallinity of the drug. The drug and formulation were found to be stable over a 6-month period in accelerated stability testing. Using high speed homogenization method, the particle size of the formulation was reduced to nano-size, which was further responsible for the improvement in dissolution and bioavailability of the drug.