Madan Jyotsana R, Kamate Virendra J, Dua Kamal, Awasthi Rajendra
Department of Pharmaceutics, Sinhgad Technical Education Society's, Smt. Kashibai Navale College of Pharmacy, Pune, Maharashtra, India.
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, Australia.
Polim Med. 2017 Jul-Dec;47(2):83-90. doi: 10.17219/pim/77093.
Nevirapine, an antiviral drug, is a potent reverse transcriptase inhibitor (NNRTI). It is used in combination with nucleoside analogues for treatment of HIV type-1 (HIV-1) infection and AIDS. Nevirapine is a BCS class II drug which shows dissolution rate limited absorption.
The aim of the present research was to provide a fast dissolving solid dispersion of nevirapine.
The solubility of nevirapine was initially determined individually in four hydrotropic agents - namely urea, lactose, citric acid and mannitol - at a concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. The highest solubility was obtained in the 40% citric acid solution. Then different combinations of 2 and 3 hydrotropic agents in different ratios were used to determine solubility, so that the total concentration of hydrotropic agents was always 40%.
The highest solubility was obtained in a solution of lactose and citric acid at the optimum ratio of 15:25. This optimized combination was utilized in preparing solid dispersions by a common solvent technique using distilled water as a solvent. The solid dispersions were evaluated for XRD, DSC and FTIR to show no drug-hydrotrope interaction.
It was concluded that the concept of mixed hydrotropic solid dispersion is a safe, novel and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs by dissolving the drug in a nonionized form. The enhancement in solubility of nevirapine using hydrotropy is a clear indication of its potential to be used in the future for other poorly water-soluble drugs in which low bioavailability is a major concern.
奈韦拉平是一种抗病毒药物，是一种强效逆转录酶抑制剂（非核苷类逆转录酶抑制剂）。它与核苷类似物联合用于治疗1型人类免疫缺陷病毒（HIV-1）感染和艾滋病。奈韦拉平是一种BCS II类药物，其吸收受溶出速率限制。
本研究的目的是提供一种奈韦拉平的速溶固体分散体。
首先分别在四种助溶剂——即尿素、乳糖、柠檬酸和甘露醇——中，以10%、20%、30%和40%（w/v）的溶液浓度，使用纯化水作为溶剂测定奈韦拉平的溶解度。在40%的柠檬酸溶液中获得了最高溶解度。然后使用不同比例的2种和3种助溶剂的不同组合来测定溶解度，以使助溶剂的总浓度始终为40%。
在乳糖和柠檬酸的溶液中，以15:25的最佳比例获得了最高溶解度。这种优化的组合被用于通过以蒸馏水为溶剂的共溶剂技术制备固体分散体。对固体分散体进行了X射线衍射（XRD）、差示扫描量热法（DSC）和傅里叶变换红外光谱（FTIR）分析，结果表明不存在药物-助溶剂相互作用。
得出的结论是，混合助溶固体分散体的概念是一种安全、新颖且具有成本效益的技术，可通过将药物以非离子化形式溶解来提高难溶性药物的生物利用度。利用助溶作用提高奈韦拉平的溶解度，明确表明其未来有潜力用于其他难溶性药物，这些药物的低生物利用度是一个主要问题。
