Physiological bicarbonate buffers: stabilisation and use as dissolution media for modified release systems
Physiological bicarbonate buffers: stabilisation and use as dissolution media for modified release systems
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DOI：
10.1016/j.ijpharm.2009.08.003
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发表时间：
2009-12-01
影响因子：
5.8
通讯作者：
Basit, Abdul W.
中科院分区：
文献类型：
--
作者：
Fadda, Hala M.;Merchant, Hamid A.;Basit, Abdul W.
Bicycle介质反映了小肠腔液的离子组成和缓冲能力。在这里，我们研究了稳定碳酸氢盐缓冲液的方法，这些方法可以很容易地应用于USP-II溶出仪。研究了三种美沙拉秦肠溶包衣产品的体外释药行为。在pH 7.4的Krebs碳酸氢盐和磷酸盐缓冲液中比较Asacol（R）400 mg和Asacol（R）800 mg（Asacol（R）HD）以及新一代高剂量（1200 mg）延迟和持续释放制剂Mezavant（R）（Lialda（R））。通过以下方式实现双稳态稳定：用5% CO2（g）连续喷射介质，在介质上方应用一层液体石蜡，或专门设计的内部密封装置，以防止CO2（g）损失。与磷酸盐缓冲液相比，每种产品在生理碳酸氢盐介质中显示出延迟的药物释放开始。此外，Mezavant（R）在磷酸盐缓冲液中显示零级持续释放曲线;然而，在碳酸氢盐介质中，这种缓慢的药物释放不再明显，并且观察到与Asacol（R）400 mg相似的曲线。在碳酸氢盐介质中显示的400 mg Asacol和Mezavant的这些相似释放模式与它们在人体中的药代动力学曲线一致。Biclitazone介质提供了一个更好的预测体内行为的美沙拉秦制剂的研究。(C)2009 Elsevier B. V.保留所有权利。
Bicarbonate media are reflective of the ionic composition and buffer capacity of small intestinal luminal fluids. Here we investigate methods to stabilise bicarbonate buffers which can be readily applied to USP-II dissolution apparatus. The in vitro drug release behaviour of three enteric coated mesalazine (mesalamine) products is investigated. Asacol (R) 400 mg and Asacol (R) 800 mg (Asacol (R) HD) and the new generation, high dose (1200 mg) delayed and sustained release formulation, Mezavant (R) (Lialda (R)), are compared in pH 7.4 Krebs bicarbonate and phosphate buffers. Bicarbonate stabilisation was achieved by: continuous sparging of the medium with 5% CO2(g), application of a layer of liquid paraffin above the medium, or a specially designed in-house seal device that prevents CO2(g) loss. Each of the products displayed a delayed onset of drug release in physiological bicarbonate media compared to phosphate buffer. Moreover, Mezavant (R) displayed a zero-order, sustained release profile in phosphate buffer; in bicarbonate media, however, this slow drug release was no longer apparent and a profile similar to that of Asacol (R) 400 mg was observed. These similar release patterns of Asacol (R) 400 mg and Mezavant (R) displayed in bicarbonate media are in agreement with their pharmacokinetic profiles in humans. Bicarbonate media provide a better prediction of the in vivo behaviour of the mesalazine preparations investigated. (C) 2009 Elsevier B.V. All rights reserved.