Development and optimization of nanoemulsion containing exemestane using box-behnken design

Exemestane (EXE) a potent third generation aromatase inhibitor and is employed as first line treatment in estrogen receptor positive breast cancer. Its oral bioavailability is only 5% due to low absorption and extensive first-pass metabolism which restricts its efficacy. The present work is aimed to develop, and characterize novel nanoemulsion containing Exemestane (EXE-NE) for transdermal application to avoid first pass metabolism. Box-Behnken experimental design was used for optimization of the independent variables including drug amount, % oil and % S mix. The mean globule size, polydispersity index (PDI), and percent drug entrapment efficiency (%DEE) were the dependent variables. The independent variables were optimized for responses employing the desirability function. The optimized exemestane containing nanoemulsion (OE-NE) consisted of linoleic acid (10%), drug (10 mg) and Smix (45.73%) with an overall desirability of 0.782. It has a mean globule size (162.1 ± 0.9797 nm), narrow PDI (0.360 ± 0.0004), high % DEE (80.00 ± 0.0047), and zeta potential (−06.36 ± 0.38). The ex-vivo skin permeation and retention studies were performed on full thickness rat skin which revealed significant improvement (p < 0.0001) in the permeation and retention of EXE (p < 0.001) from OE-NE as compared with control (aqueous suspension). The permeation coefficient (Kp) of EXE from OE-NE was enhanced by ∼3.33 times vis-à-vis EXE-S. The histopathological and skin irritation studies revealed safety of the optimized formulation. The present study showed a successful preparation of a stable EXE loaded NE with enhanced skin permeation, retention and no skin irritation. Thus, it can be a promising potential alternative to conventional EXE formulation for managing estrogen receptor positive breast cancer.