Laboratory of Nanotechnology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, India.
Drug Dev Ind Pharm. 2021 Apr;47(4):618-625. doi: 10.1080/03639045.2021.1908332. Epub 2021 Apr 7.
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 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).
依匹哌唑（IL）在水中几乎不溶，具有显著的首过代谢，导致其在人体中的口服生物利用度低（36%）。IL 脂质纳米乳液（IL-LNEs）被制备以提高口服生物利用度。IL-LNEs 通过热匀化和超声处理方法制备。使用不同浓度的大豆油和蛋黄卵磷脂作为乳化剂来制备 LNEs。动态光散射技术用于粒径分析。所有 LNE 制剂均表现出窄的粒径分布，平均粒径和多分散指数（PDI）分别在 182.2±2.8 至 222.3±1.9nm 和 0.200±0.004 至 0.274±0.005 之间。Zeta 电位值在-20.0±0.15 至-28.9±0.30mV 之间变化，表明制备的 LNEs 稳定。当使用 centrisart 管分离时，所有制剂的包封效率均良好，范围为 99.07±0.01%至 99.28±0.01%，药物含量在 96.99±0.94%至 99.06±0.36%之间变化。物理稳定性测试表明所有 LNEs 均稳定，优化后的 LNE-IL4 在冷藏（4°C）和室温（25°C）下均稳定 3 个月。在 Wistar 大鼠研究中，与市售片剂混悬剂（Ilosure-4）相比，优化后的 LNE 使口服生物利用度提高了 2.47 倍，对 MK-801（地卓西平）诱导的过度活动的药效提高了 1.22 倍。
