Investigation of In Vivo Bioavailability Enhancement of Iloperidone-Loaded Solid Self-Nanoemulsifying Drug Delivery Systems: Formulation and Optimization Using Box-Behnken Design and Desirability Function.

Purpose: The current research focuses on enhancement of in vitro dissolution and in vivo bioavailability characteristics of iloperidone (IP) by formulation, optimization of L-SNEDDS using Box-Behnken design (BBD), and desirability function. L-SNEDDS were transformed into free-flowing powders by adsorption onto Neusilin US2 carrier. Methods: The excipients for formulation of SNEDDS (oils, surfactants, and co-surfactants) were selected based on drug solubility and their emulsification ability. For optimization of the formulation, four response variables such as globule size (nm), percentage transmittance (%), self-emulsification time (sec), and percent drug released in 15 min were considered. The 2D contour plots and 3D response surface plots were constructed using Design Expert software. Optimized formulation by adsorption method was converted to S-SNEDDS that were characterized by FTIR, DSC, SEM, and PXRD analyses. They were evaluated for particle size, polydispersity index, (PDI) and zeta potential. Results: The developed optimal L-SNEDDS of IP through BBD approach resulted in improvement of solubility and dissolution rate as compared with the pure drug. The characterization studies revealed droplet size to be 21.80 ± 2.41 nm, 99.584 ± 0.65% transmittance, 24.43 ± 2.12-sec emulsification time, and 95.31 ± 1.57% cumulative drug release in 15 min. The in vivo pharmacokinetic studies revealed that the optimized formulation showed an improvement in bioavailability when studied in Wistar rats in comparison with oral suspension of drug. Solid state characterization studies concluded lack of any significant interactions of drug with the lipid excipients and porous carriers. Accelerated stability studies emphasized stability of the product. Conclusion: The results conclude the potentiality of optimization of L-SNEDDS by application of BBD and desirability function and improvement in bioavailability by S-SNEDDS on oral administration. [ABSTRACT FROM AUTHOR]