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.