UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK; Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Int J Pharm. 2015 Apr 30;484(1-2):103-8. doi: 10.1016/j.ijpharm.2015.02.051. Epub 2015 Feb 23.
The aminosalicylate mesalazine (mesalamine) forms the mainstay of treatment in ulcerative colitis (UC), a disease for which many commercial modified-release products have been developed with the aim of providing targeted gastrointestinal release. The release profiles of five of these commercial formulations were evaluated in bicarbonate buffer using a novel dissolution model that mimics the dynamic conditions of the gastrointestinal tract. Monolithic and multi-particulate mesalazine formulations with pH-dependent and/or independent release mechanisms were evaluated (Asacol(®) 800, Octasa(®), Mezavant(®) XL, Salofalk(®), Pentasa(®)), and each of the products displayed a distinctive dissolution profile. The dissolution results for Mezavant(®) XL (Lialda(®)) (lag time 290 min) demonstrated good correlation with previously reported in vivo disintegration times assessed by gamma-scintigraphy in humans. Octasa(®) showed a similar lag time to Mezavant(®) XL. Drug release from Asacol(®) 800 (Asacol(®) HD) showed a wide standard deviation, reflecting the great variability in vivo. Salofalk(®) displayed both delayed release and extended release characteristics. Pentasa(®) released more than 50% of its drug load in the stomach compartment of the model, which is attributed to the absence of a gastro-resistant coating in this product. The new dissolution method provided a realistic and discriminative in vitro assessment of mesalazine release from different formulations. These results demonstrate that this strategy can be used to predict intestinal release behaviour, and potentially aid the rational design of products developed to target different sites of the gut.
柳氮磺胺吡啶（mesalazine）是溃疡性结肠炎（UC）的主要治疗药物，为此已经开发了许多商业改良释放产品，旨在提供靶向胃肠道释放。使用模拟胃肠道动态条件的新型溶解模型评估了其中五种商业制剂的释放曲线。评估了具有 pH 依赖性和/或非依赖性释放机制的单块和多颗粒 mesalazine 制剂（Asacol®800、Octasa®、Mezavant®XL、Salofalk®、Pentasa®），每种产品都显示出独特的溶解曲线。Mezavant®XL（Lialda®）（滞后时间 290 分钟）的溶解结果与先前通过人体γ闪烁照相术评估的体内崩解时间具有良好的相关性。Octasa®与 Mezavant®XL 具有相似的滞后时间。Asacol®800（Asacol®HD）的药物释放显示出较大的标准偏差，反映了体内的巨大变异性。Salofalk®显示出延迟释放和延长释放的特征。Pentasa®在模型的胃腔中释放了超过 50%的药物负荷，这归因于该产品中没有胃耐涂层。新的溶解方法为不同制剂的 mesalazine 释放提供了真实和有区别的体外评估。这些结果表明，该策略可用于预测肠道释放行为，并可能有助于针对肠道不同部位开发的产品的合理设计。
