Pharmacokinetic and pharmacodynamic studies of iloperidone-loaded lipid nanoemulsions via oral route of administration

Abstract

Iloperidone (IL) is practically insoluble in water and has significant first-pass metabolism, resulting in low oral bioavailability in humans (36%). IL lipid nanoemulsions (IL-LNEs) were prepared to improve oral bioavailability. IL-LNEs were formulated by hot homogenization and ultrasonication method. Soybean oil and egg lecithin in various concentrations as emulsifier were used in the preparation of LNEs. Dynamic light scattering technique was used for globule size analysis. All LNE formulations showed narrow size distribution and the average globule size and Poly Dispersity Index (PDI) were found to be in between 182.2 ± 2.8 to 222.3 ± 1.9 nm and 0.200 ± 0.004 to 0.274 ± 0.005 respectively. Zeta potential values varied from −20.0 ± 0.15 to −28.9 ± 0.30 mV which indicated stability of prepared LNEs. All formulations showed good entrapment efficiency ranging from 99.07 ± 0.01 to 99.28 ± 0.01% when separated using centrisart tubes and the drug content varied from 96.99 ± 0.94 to 99.06 ± 0.36%. Physical stability testing indicated the stability of all LNEs and optimized LNE-IL4 was found stable for 3 months at both refrigerated (4 °C) and room temperature (25 °C). During in vivo studies in wistar rats, the optimized LNE showed 2.47-fold improvement in the oral bioavailability and superior (1.22-fold) pharmacodynamic activity when compared to marketed tablet suspension (Ilosure-4®) in suppressing the hyperlocomotor activity, being induced by MK-801 (Dizocilpine).