Takeuchi Susumu, Tsume Yasuhiro, Amidon Gregory E, Amidon Gordon L
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065; Pharmacokinetics group, Sawai Pharmaceutical Company, Ltd, Osaka 532-0003, Japan.
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065.
J Pharm Sci. 2014 Nov;103(11):3416-3422. doi: 10.1002/jps.24112. Epub 2014 Sep 22.
In vitro dissolution tests are performed for new formulations to evaluate in vivo performance, which is affected by the change of gastrointestinal (GI) physiology, in the GI tract. Thus, those environmental changes should be introduced to an in vitro dissolution test. Many studies have successfully shown the improvement of in vitro-in vivo correlations (IVIVC) by introducing those physiological changes into dissolution tests. The gastrointestinal simulator (GIS), a multicompartment in vitro dissolution apparatus, was developed to evaluate in vivo drug dissolution. A gastric-emptying rate along with transit rate are key factors to evaluate in vivo drug dissolution and, hence, drug absorption. Dissolution tests with the GIS were performed with Biopharmaceutical Classification System class I drugs at five different gastric-emptying rates in the fasted state. Computational models were used to determine in vivo gastric-emptying time for propranolol and metoprolol based on the GIS dissolution results. Those were compared with published clinical data to determine the gastric half-emptying time. In conclusion, the GIS is a practical tool to assess dissolution properties and can improve IVIVC.
对新制剂进行体外溶出试验以评估其体内性能，而体内性能会受到胃肠道（GI）生理变化的影响。因此，应将这些环境变化引入体外溶出试验。许多研究已成功表明，通过将这些生理变化引入溶出试验可改善体外-体内相关性（IVIVC）。胃肠道模拟器（GIS）是一种多隔室体外溶出装置，用于评估体内药物溶出情况。胃排空速率和转运速率是评估体内药物溶出以及药物吸收的关键因素。在禁食状态下，使用GIS对生物药剂学分类系统I类药物以五种不同的胃排空速率进行了溶出试验。基于GIS溶出结果，使用计算模型确定了普萘洛尔和美托洛尔的体内胃排空时间。将这些结果与已发表的临床数据进行比较，以确定胃半排空时间。总之，GIS是评估溶出特性的实用工具，可改善IVIVC。
