Radwan Asma, Wagner Manfred, Amidon Gordon L, Langguth Peter
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Max Planck Institute for Polymer Research, Mainz, Germany.
Eur J Pharm Sci. 2014 Jun 16;57:273-9. doi: 10.1016/j.ejps.2013.08.038. Epub 2013 Sep 11.
Food intake may delay tablet disintegration. Current in vitro methods have little predictive potential to account for such effects. The effect of a variety of factors on the disintegration of immediate release tablets in the gastrointestinal tract has been identified. They include viscosity of the media, precipitation of food constituents on the surface of the tablet and reduction of water diffusivity in the media as well as changes in the hydrodynamics in the surrounding media of the solid dosage form. In order to improve the predictability of food affecting the disintegration of a dosage form, tablet disintegration in various types of a liquefied meal has been studied under static vs. dynamic (agitative) conditions. Viscosity, water diffusivity, osmolality and Reynolds numbers for the different media were characterized. A quantitative model is introduced which predicts the influence of the Reynolds number in the tablet disintegration apparatus on the disintegration time. Viscosity, water diffusivity and media flow velocity are shown to be important factors affecting dosage form disintegration. The results suggest the necessity of considering these parameters when designing a predictive model for simulating the in vivo conditions. Based on these experiments and knowledge on in vivo hydrodynamics in the GI tract, it is concluded that the disintegration tester under current pharmacopoeial conditions is operated in an unphysiological mode and no bioprediction may be derived. Recommendations regarding alternative mode of operation are made.
食物摄入可能会延迟片剂崩解。目前的体外方法几乎没有预测此类影响的潜力。已确定多种因素对速释片剂在胃肠道中崩解的影响。这些因素包括介质的粘度、食物成分在片剂表面的沉淀、介质中水扩散率的降低以及固体剂型周围介质中流体动力学的变化。为了提高食物对剂型崩解影响的可预测性，已研究了在静态与动态（搅拌）条件下，各种类型的液化餐食中片剂的崩解情况。对不同介质的粘度、水扩散率、渗透压和雷诺数进行了表征。引入了一个定量模型，该模型可预测片剂崩解装置中的雷诺数对崩解时间的影响。粘度、水扩散率和介质流速被证明是影响剂型崩解的重要因素。结果表明，在设计模拟体内条件的预测模型时，有必要考虑这些参数。基于这些实验以及对胃肠道内体流体动力学的了解，得出结论：当前药典条件下的崩解测试仪处于非生理模式运行，无法得出生物预测结果。并针对替代操作模式提出了建议。
