Purpose:
Present investigation was aimed to fabricate nanocrystal of exemestane, an anticancer drug with poor
dissolution properties and oral bioavailability.
Methods:
Influence of various process parameters on the formulation of exemestane nanosuspension using media milling
technique were investigated in the trial batches. Box-Behnken design was applied with independent variables identified in
the preliminary studies, viz. X1-Milling time, X2-Amount of stabilizer and X3-Amount of milling agent. In vitro dissolution
and in vivo studies were carried out. Solid state characterization (PXRD, SEM, and DSC) studies demonstrated physical
changes in drug due to nano-crystallization. Accelerated stability studies of optimized formulation were carried out.
Results:
Individual process attributes exhibited significant effect on the average particle size of exemestane nanosuspension.
Dissolution studies revealed enhancement in drug release rate as compared to pure exemestane powder. The in vivo
pharmacokinetic parameters of exemestane nanosuspension showed significant improvement in Cmax and AUC0-t, about
283.85% and 271.63% respectively suggesting amelioration in oral bioavailability by 2.7-fold as compared to pure
exemestane. Accelerated stability studies of the optimized formulation suggested stability of the nanocrystals for at least sixmonth
period.
Conclusion:
Nanocrystals prepared by media milling technique were successful in improving the poor dissolution properties
and oral bioavailability of exemestane.