University of Greifswald, Institute of Pharmacy, Friedrich-Ludwig-Jahn-Strasse 17, Greifswald, Germany.
Expert Opin Drug Deliv. 2010 Nov;7(11):1251-61. doi: 10.1517/17425247.2010.527943.
The prediction of the in vivo drug release characteristics of modified release (MR) oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development.
To improve the predictive power of dissolution testing, the authors recently developed a new dissolution test apparatus that simulates physical conditions of the gastrointestinal (GI) passage of MR dosage forms. The simulation includes pressure force exerted by GI motility, shear stress force generated during phases of GI transport and intermittent contact with intestinal fluids while the dosage form is located in an intestinal air pocket.
The article briefly describes selected aspects of GI tract physiology, evolution and goals of dissolution testing as well as the development and use of test devices that are intended to simulate GI tract conditions. The data are discussed in the light of the test results obtained with the new dissolution stress test device developed by the authors' group. Achievements reported from 1986 to 2010 are referred to.
The new apparatus was evaluated using extended release (ER) tablets of nifedipine and diclofenac. The dissolution characteristics of some of the tested products were strongly dependent on the test conditions and could be distinctly influenced by the mechanical stress events of biorelevant intensity. Results of these experiments thus indicated that a high sensitivity of dosage forms to GI-specific physical conditions has to be regarded as a major cause of irregularities in the drug release profiles, which may result in fluctuations of the individual drug plasma concentration profiles, as, for example, caused by dose dumping.
通过体外溶出试验预测改性释放（MR）口服剂型的体内药物释放特性是成功产品开发的前提。
为了提高溶出试验的预测能力，作者最近开发了一种新的溶出试验仪器，模拟了 MR 剂型在胃肠道（GI）通过时的物理条件。模拟包括 GI 蠕动施加的压力、GI 输送过程中产生的剪切应力以及剂型位于肠气袋中时与肠液间歇性接触。
本文简要描述了胃肠道生理学的某些方面、溶出试验的发展和目标以及旨在模拟胃肠道条件的试验设备的开发和使用。讨论数据时参考了作者小组开发的新型溶出应力量测试设备获得的测试结果。引用了 1986 年至 2010 年的报告成就。
新仪器使用硝苯地平和双氯芬酸的控释（ER）片剂进行了评估。一些测试产品的溶解特性强烈依赖于测试条件，并且可以明显受到具有生物相关性强度的机械应力事件的影响。这些实验的结果表明，剂型对胃肠道特定物理条件的高敏感性必须被视为不规则药物释放曲线的主要原因之一，这可能导致个体药物血浆浓度曲线波动，例如由于剂量突然释放引起的波动。
