Research from the past decade has shown that the buffer capacities of intestinal fluids are much lower than those in the media used for dissolution test of many solid formulations. The purpose of this study was to elucidate the effect of buffer capacity on the dissolution profiles of highly soluble drug products, using metoclopramide (a biopharmaceutics classification system [BCS] class III drug) tablets as a model. The dissolution profiles of three metoclopramide products were obtained in Japanese pharmacopeia dissolution medium (pH 1.2 and 6.8), diluted medium with low buffer capacity comparable to that of gastrointestinal fluid, and other biorelevant media. One product showed slower dissolution in the medium with lower buffer capacity (bio-relevant, diluted compendial solution), but substantially similar dissolution in the compendial test solutions. Disintegration difference was implied to be involved in the different dissolution profiles depending on the medium buffer capacity. This study indicated the importance of media buffer capacity as a factor inducing different dissolution between products of highly soluble active pharmaceutical ingredients. The diluted compendial media would be a useful alternative to biorelevant media for the detection of the different formulation performances depending on the buffer capacities.

中文翻译：

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利用稀释的药典培养基作为低缓冲容量的溶出度测试溶液，以研究高可溶性速释药物产品的溶出度。

过去十年的研究表明，肠液的缓冲能力远低于许多固体制剂溶出度测试所用介质的缓冲能力。这项研究的目的是使用甲氧氯普胺（一种生物药物分类系统[BCS] III类药物）片剂作为模型，阐明缓冲剂容量对高溶解性药物溶出曲线的影响。在日本药典溶出介质（pH 1.2和6.8），具有与胃肠液相当的低缓冲容量的稀释介质以及其他生物相关介质中获得了三种甲氧氯普胺产品的溶出曲线。一种产品显示在具有较低缓冲容量（生物相关的稀释药典溶液）的培养基中溶解较慢，但在药典测试溶液中的溶出度基本相似。取决于介质缓冲能力，暗示崩解差异涉及不同的溶出曲线。这项研究表明，介质缓冲容量作为引起高可溶性活性药物成分产品之间不同溶出度的因素的重要性。稀释的药典培养基将是生物相关培养基的有用替代品，用于检测取决于缓冲液容量的不同制剂性能。这项研究表明，介质缓冲容量作为引起高可溶性活性药物成分产品之间不同溶出度的因素的重要性。稀释的药典培养基将是生物相关培养基的有用替代品，用于检测取决于缓冲液容量的不同制剂性能。这项研究表明，介质缓冲容量作为引起高可溶性活性药物成分产品之间不同溶出度的因素的重要性。稀释的药典培养基将是生物相关培养基的有用替代品，用于检测取决于缓冲液容量的不同制剂性能。