Chudasama Arpan, Patel Vineetkumar, Nivsarkar Manish, Vasu Kamala, Shishoo Chamanlal
Department of Pharmaceutics .
Drug Deliv. 2015;22(4):531-40. doi: 10.3109/10717544.2014.891270. Epub 2014 Mar 7.
The objective of this study was to develop self-emulsifying drug delivery system (SEDDS) to improve solubility and enhance the oral absorption of the poorly water-soluble drug, nevirapine. This lipid-based formulation may help to target the drug to lymphoid organs where HIV-1 virus resides mainly. The influence of the oil, surfactant and co-surfactant types on the drug solubility and their ratios on forming efficient and stable SEDDS were investigated in detail. Two SEDDS (F1 and F2) were prepared and characterized by morphological observation, droplet size and zeta potential determination, cloud point measurement and in vitro diffusion study. The influence of droplet size on the absorption from formulations with varying concentration of oil and surfactant was also evaluated from two self-emulsifying formulations. Oral bioavailability of nevirapine SEDDS was checked by using rat model. Results of diffusion rate and oral bioavailability of nevirapine SEDDS were compared with marketed suspension. The absorption of nevirapine from F1 and F2 showed 1.92 and 1.98-fold increase (p < 0.05) in relative bioavailability, respectively, compared with that of the suspension. There was no statistical significant difference (p < 0.05) between F1 and F2 in their AUC and C(max). This indicated that there was apparent poor correlation between the droplet size and in vivo absorption. However, nevirapine in SEDDS showed higher ex vivo stomach and intestinal permeability and in vivo absorption than the marketed suspension, suggesting that the SEDDS may be a useful delivery system for targeting nevirapine to lymphoid organs.
本研究的目的是开发自乳化药物递送系统（SEDDS），以提高难溶性药物奈韦拉平的溶解度并增强其口服吸收。这种基于脂质的制剂可能有助于将药物靶向至HIV-1病毒主要驻留的淋巴器官。详细研究了油相、表面活性剂和助表面活性剂的类型对药物溶解度的影响以及它们的比例对形成高效稳定的SEDDS的影响。制备了两种SEDDS（F1和F2），并通过形态观察、液滴大小和zeta电位测定、浊点测量以及体外扩散研究进行表征。还从两种自乳化制剂评估了液滴大小对不同油相和表面活性剂浓度制剂吸收的影响。使用大鼠模型检查了奈韦拉平SEDDS的口服生物利用度。将奈韦拉平SEDDS的扩散速率和口服生物利用度结果与市售混悬剂进行了比较。与混悬剂相比，F1和F2中奈韦拉平的吸收相对生物利用度分别提高了1.92倍和1.98倍（p < 0.05）。F1和F2在AUC和C(max)方面无统计学显著差异（p < 0.05）。这表明液滴大小与体内吸收之间明显缺乏相关性。然而，SEDDS中的奈韦拉平比市售混悬剂显示出更高的离体胃和肠道通透性以及体内吸收，这表明SEDDS可能是将奈韦拉平靶向至淋巴器官的一种有用的递送系统。
