Effects of different cellulose derivatives on drug release mechanism studied at a preformulation stage
Effects of different cellulose derivatives on drug release mechanism studied at a preformulation stage
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DOI：
10.1016/j.jconrel.2003.11.009
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发表时间：
2004-02-20
影响因子：
10.8
通讯作者：
Pourcelot, Y
中科院分区：
文献类型：
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作者：
Chambin, O;Champion, D;Pourcelot, Y
事实上，众所周知，体外溶出是制药工业开发有效药物的首选方法。然而，许多实验必须在新产品的整个生命周期沿着进行，这对研究人员来说是一种过度的负担。本文的目的是通过核磁共振（NMR）实验评估预配制阶段获得的新参数的相关性，以更好地了解药物释放机制。本研究采用目前用作载体基质的三种纤维素衍生物（微晶纤维素（MCC）、羟丙基甲基纤维素（HPMC）和乙基纤维素（EC））进行。用这三种赋形剂（60%w/w）和作为药物模型的茶碱（40%）制备颗粒剂和片剂。一方面，用旋转桨法进行体外溶出研究，显示这三种基质的不同释放行为（MCC的速释、HPMC的稳定释放和EC的缓释）。另一方面，记录了颗粒水化过程中核磁共振实验中T-2 m自旋-自旋弛豫时间的演变。核磁共振结果海岸上升溶解数据，两者都取决于基质和水之间的相互作用。核磁共振波谱法似乎是一个有价值的工具，获得，在药物开发的早期阶段，更多的信息，药物释放机制。(C)2004 Elsevier B. V.保留所有权利。
As a matter of fact, in vitro dissolution is well known to be the method of choice for the pharmaceutical industry to develop effective medicines. However, many experiments must be performed all along a new product life and they represent an overcharge of work for researchers. The purpose of this paper was to assess the relevance of new parameters obtained during preformulation stage by Nuclear Magnetic Resonance (NMR) experiments to better understand drug release mechanism. This study was carried out with three cellulose derivatives currently used as carrier matrices (Microcrystalline cellulose (MCC), Hydroxypropylmethyl cellulose (HPMC) and Ethyl cellulose (EC)). Granules and tablets were produced with these three excipients (60% w/w) and theophylline as drug model (40%). On the one hand, in vitro dissolution studies were performed with the rotating paddle method displaying the different release behaviour of these three matrices (immediate release for MCC, steady release for HPMC and sustained release for EC). On the other hand, the evolution of the T-2m spin-spin relaxation time in NMR experiments during granules hydration was recorded. NMR findings shore up dissolution data, both depending on interactions between the matrix and water. NMR spectroscopy appears to be a valuable tool for obtaining, at an earlier stage of drug development, more information about drug release mechanism. (C) 2004 Elsevier B.V. All rights reserved.