Objective: The aim of the present investigation entails the development and optimization of self-microemulsion preconcentrates for improving the solubility and oral bioavailability of aprepitant.
Methods: Preconcentrate ingredients, i.e. oils, surfactants and co-surfactants were selected on the basis of equilibrium solubility studies. Ternary plots were constructed to determine stable microemulsion regions and determine optimized concentration ranges for robust preconcentrate formulations of aprepitant. Various characterization parameters were studied to investigate the optimized formulation having desired attributes of SMEDDS. Dissolution and pharmacokinetics studies were conducted to determine the release rate and oral bioavailability, respectively.
Results: The optimized formulation containing 7.14%w/w of Lauroglycol FCC, 36.14 %w/w of Labrasol and 32.14%w/w of Transcutol P exhibited optical birefringence and resulted in thermodynamically stable nano-particulate emulsion. TEM revealed morphological behavior with nano-structured globules having negligible aggregation. The optimized liquid SMEDDS were converted into solid form by spray drying and showed physical compatibility in FTIR and confirmed its amorphous state in XRD pattern. SEM revealed spherical particles having colloidal nature with uniform size distribution. In vitro release studies of optimized solid preconcentrates showed multi folds augmentation in release behavior and statistical significance (P<0.05) as compared with marketed product. In vivo pharmacokinetics in male wistar rats demonstrated statistically (P<0.05) enhanced AUC0-24h and Cmax as compared with API and marketed product. Accelerated stability studies signify high stability of the robust formulation at one month storage period of time.
Conclusion: The present investigation judiciously extrapolated the immense potential of SMEDDS in enhancing the solubility and oral bioavailability of poorly water-soluble anti-emetic drug aprepitant.