Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs
Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs
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DOI：
10.1016/j.ijpharm.2006.01.008
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发表时间：
2006-04-07
影响因子：
5.8
通讯作者：
Kristl, J
中科院分区：
文献类型：
--
作者：
Kocbek, P;Baumgartner, S;Kristl, J
水溶性差的化合物难以使用常规制剂技术开发为药物产品，并且经常在发现早期被放弃。本研究将传统制备固体脂质纳米粒的熔融乳化法用于制备药物纳米混悬剂。与众所周知的溶剂扩散过程中布洛芬作为模型药物进行了比较，该方法进行了评价。控制制备变量（稳定剂、药物含量、均质化程序和冷却条件）允许形成直径小于100 nm的纳米混悬液。与溶剂扩散法相比，熔融乳化法的主要优点是在生产过程中避免了有机溶剂，尽管平均粒度略大。吐温80和PVP K25作为稳定剂的组合产生具有最小平均粒度的纳米悬浮液。布洛芬作为冻干粉末或颗粒形式的纳米混悬液的制剂在提高溶出速率方面非常成功，与小于15%的微粉化药物相比，超过65%的药物在前10分钟内溶解。体外溶出速率的增加可能会有利地影响生物利用度，并通过降低胃刺激性来改善患者的安全性。(c)2006 Elsevier B.V.保留所有权利。
Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt emulsification method traditionally used to prepare solid lipid nanoparticles was adapted to produce drug nanosuspensions. The method was evaluated in comparison with the well known solvent diffusion process for ibuprofen as a model drug. Control of the preparation variables (stabilizers, drug content, homogenization procedure and cooling conditions) allowed formation of nanosuspensions with diameters less than 100 nm. The major advantage of the melt emulsification method over the solvent diffusion method is the avoidance of organic solvents during production, although the mean particle size is slightly greater. The combination of Tween 80 and PVP K25 as stabilizers yields nanosuspensions with the smallest average particle size. The formulation of ibuprofen as a nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more than 65% of the drug being dissolved in the first 10 min compared to less than 15% of the micronized drug. The increase in in vitro dissolution rate may favourably affect bioavailability and improve safety for the patient by decreasing gastric irritancy. (c) 2006 Elsevier B.V. All rights reserved.