Nanomemulsion of megestrol acetate for improved oral bioavailability and reduced food effect

Megestrol acetate (MGA) belongs to the BCS class II drugs with low solubility and high permeability, and its oral absorption in conventional dosage form MGA microcrystal suspension (MGA MS) is very limited and greatly affected by food. In this study, MGA nanoemulsion (MGA NE) was formulated based on solubility, phase-diagram and release studies. Then oral bioavailability of MGA NE and MGA MS was evaluated. A randomized two-way crossover trial was conducted on six male dogs under fed and fasting conditions. Blood concentrations of MGA were analyzed using LC–MS/MS. MGA NE yielded 5.00-fold higher oral bioavailability in fasting conditions and displayed more stable absorption profiles after food intake compared with MGA MS.