Schneider Felix, Koziolek Mirko, Weitschies Werner
Department of Biopharmaceutics and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, 17489 Greifswald, Germany.
Pharmaceutics. 2019 Aug 16;11(8):416. doi: 10.3390/pharmaceutics11080416.
More than 50 years ago, the first concepts for gastroretentive drug delivery systems were developed. Despite extensive research in this field, there is no single formulation concept for which reliable gastroretention has been demonstrated under different prandial conditions. Thus, gastroretention remains the holy grail of oral drug delivery. One of the major reasons for the various setbacks in this field is the lack of predictive in vitro and in vivo test methods used during preclinical development. In most cases, human gastrointestinal physiology is not properly considered, which leads to the application of inappropriate in vitro and animal models. Moreover, conditions in the stomach are often not fully understood. Important aspects such as the kinetics of fluid volumes, gastric pH or mechanical stresses have to be considered in a realistic manner, otherwise, the gastroretentive potential as well as drug release of novel formulations cannot be assessed correctly in preclinical studies. This review, therefore, highlights the most important aspects of human gastrointestinal physiology and discusses their potential implications for the evaluation of gastroretentive drug delivery systems.
五十多年前，胃滞留型药物递送系统的最初概念被提出。尽管该领域进行了广泛研究，但尚无一种单一的制剂概念能在不同用餐条件下被证明具有可靠的胃滞留效果。因此，胃滞留仍然是口服药物递送的圣杯。该领域各种挫折的主要原因之一是临床前开发过程中缺乏预测性的体外和体内测试方法。在大多数情况下，人体胃肠道生理学未得到充分考虑，这导致采用了不恰当的体外和动物模型。此外，胃部状况往往未被完全理解。诸如液体量动力学、胃pH值或机械应力等重要方面必须以实际的方式加以考虑，否则，新制剂的胃滞留潜力以及药物释放情况在临床前研究中就无法得到正确评估。因此，本综述强调了人体胃肠道生理学的最重要方面，并讨论了它们对胃滞留型药物递送系统评估的潜在影响。
