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基于混合表面活性剂的(SNEDDS)自微乳药物传递系统,呈现依非韦伦,以提高口服生物利用度。

Mixed surfactant based (SNEDDS) self-nanoemulsifying drug delivery system presenting efavirenz for enhancement of oral bioavailability.

机构信息

Department of Pharmaceutics, Sri Jayadev College of Pharmaceutical Sciences, Naharkanta, Bhubaneswar 752101, Odisha, India; University Department of Pharmaceutical Sciences, Utkal University, Vanivihar, Bhubaneswar 751004, Odisha, India.

University Department of Pharmaceutical Sciences, Utkal University, Vanivihar, Bhubaneswar 751004, Odisha, India.

出版信息

Biomed Pharmacother. 2016 May;80:42-51. doi: 10.1016/j.biopha.2016.02.039. Epub 2016 Mar 14.


DOI:10.1016/j.biopha.2016.02.039
PMID:27133038
Abstract

This study aims to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on non-ionic surfactant mixtures to improve the oral bioavailability of efavirenz (EFZ) categorized as a class II according to the BCS, for HIV- therapy. The result of solubility studies of EFZ in various excipients utilized for construction of the pseudo ternary phase diagram containing surfactant mixtures. Surfactants in 1:1 combination are used with different co-surfactants in different ratio to delineate the area of monophasic region of the pseudo ternary phase diagram. Different accelerated physical stability studies and self-emulsification assessment were performed on the formulations. The formulations clearing the above studies are considered for percentage transmittance and turbidity analysis. The globule size distributions of post diluted SNEDDS having percentage transmittance above 90 were estimated. The TEM analysis of two optimized post diluted SNEDDS formulations further confirm the size in nanometric range (below 50nm). FT-IR studies showed the retention of the characteristic peaks of EFZ in the preconcentrate. The in vitro dissolution profile of SNEDDS established advantages of SNEDDS over plain drug as more than 80% drug was released within 30min in case of optimized SNEDDS while it was approximately 18.3% in the case of plain drug powder. Pharmacokinetic parameters were calculated after performing the in vivo studies of best optimized formulation in rats. The Pharmacokinetic data reveal a 2.63 fold increase in AUC(0-∞) in comparison to plain EFZ suspension. The designed delivery system showed the faith in generating an effective formulation of EFZ for HIV treatment.

摘要

本研究旨在开发基于非离子表面活性剂混合物的自微乳给药系统(SNEDDS),以提高被归类为 BCS 类 II 的依非韦伦(EFZ)的口服生物利用度,EFZ 用于 HIV 治疗。在用于构建包含表面活性剂混合物的伪三元相图的各种赋形剂中对 EFZ 的溶解度研究的结果。表面活性剂以 1:1 的组合与不同的共表面活性剂以不同的比例使用,以描绘伪三元相图的单相区域的区域。对制剂进行了不同的加速物理稳定性研究和自乳化评估。通过上述研究的制剂被认为用于百分比透光率和浊度分析。具有大于 90%的百分比透光率的后稀释 SNEDDS 的液滴尺寸分布进行了估计。具有大于 90%的百分比透光率的两个优化的后稀释 SNEDDS 制剂的 TEM 分析进一步证实了纳米级尺寸(低于 50nm)。FT-IR 研究表明在预浓缩物中保留了 EFZ 的特征峰。SNEDDS 的体外溶解曲线表明,与普通药物相比,SNEDDS 具有优势,因为在优化的 SNEDDS 中,超过 80%的药物在 30 分钟内释放,而在普通药物粉末中,释放约 18.3%。在大鼠中进行最佳优化制剂的体内研究后计算了药代动力学参数。药代动力学数据显示与普通 EFZ 混悬剂相比,AUC(0-∞)增加了 2.63 倍。设计的传递系统表明有信心为 HIV 治疗生成有效的 EFZ 制剂。

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