Design and characterization of submicron formulation for a poorly soluble drug: The effect of Vitamin E TPGS and other solubilizers on skin permeability enhancement
Design and characterization of submicron formulation for a poorly soluble drug: The effect of Vitamin E TPGS and other solubilizers on skin permeability enhancement
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DOI：
10.1016/j.ijpharm.2012.05.031
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发表时间：
2012-09-15
影响因子：
5.8
通讯作者：
Michniak-Kohn, Bozena
中科院分区：
文献类型：
--
作者：
Ghosh, Indrajit;Michniak-Kohn, Bozena
在透皮给药系统(TDDS)中，要获得稳定和持久的高渗透速率是一个挑战，因为药物在骨架中的溶解浓度必须很高，才能保持零级释放动力学。已经报道了几种利用过饱和系统来改善难溶药物化合物的渗透性的尝试，然而，由于热力学的挑战，药物在配制后立即成核甚至在储存过程中成核的可能性很高。本文主要研究了不同增溶剂对亚微米/纳米级药物晶体的渗透效率的影响。以布洛芬为模型药物，考察了增溶剂Pluronic F-127、VE、TPGS、丙二醇对布洛芬亚微米混悬液体系的影响。考察了羟丙基甲基纤维素(HPMC)和聚乙烯吡咯烷酮(PVP)等稳定剂在亚微米范围内对药物颗粒生长的抑制作用。增溶剂的存在和亚微米药物晶体的存在似乎影响了整个皮肤的渗透促进过程。最有前景的稳定处方是维生素E TPGS+HPMC亚微米混悬剂，与其他制剂相比，它具有更高的渗透速率。(C)2012爱思唯尔B.V.保留所有权利。
In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable and prolonged high permeation rates across the skin since the concentrations of the drug dissolved in the matrix have to be high in order to maintain zero order release kinetics. Several attempts have been reported to improve the permeability of poorly soluble drug compounds using supersaturated systems, however, due to thermodynamic challenges, there was a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of drug crystals at the submicron/nano range in presence of different solubilizers to improve the permeation rate. Effect of several solubilizers, e.g. Pluronic F-127, Vitamin E TPGS, propylene glycol were studied on the submicron suspension systems of ibuprofen as a model drug. Various stabilizers such as hydroxylpropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were examined to evaluate their crystal inhibitory effects on particle growth of the drug compound at submicron range. The overall permeation enhancement process through the skin seems to be influenced by the presence of solubilizers and also the presence of submicron drug crystal. The most promising stable formulation was developed with Vitamin E TPGS + HPMC submicron suspension, which produced higher permeation rate compared to other vehicles. (c) 2012 Elsevier B.V. All rights reserved.