Office of New Animal Drug Evaluation, Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA), Rockville, Maryland, USA.
Pion Inc, Billerica, Maryland, USA.
AAPS J. 2022 May 2;24(3):60. doi: 10.1208/s12248-022-00711-3.
Traditionally, excipients have been considered in drug development from the perspective of their influence on drug solubility, manufacturability, and ability to control in vitro and in vivo drug release. These effects have been largely evaluated through studies involving in vitro dissolution methods. However, there is a growing awareness that what had previously been considered biologically inert excipients can exert numerous in vivo effects. This includes the potential to change gastrointestinal (GI) transit time, enterocyte passive transcellular or paracellular permeability, active transport activity, or presystemic drug metabolism. In this critical overview of the biological effects of excipients (Part I), we provide a summary of select published studies that explore these various in vivo factors. We also include a table that points readers to published reviews that list a range of excipients known to have biological activity. A subsequent discussion on in vitro, in vivo, and in silico methods that can be used to explore these excipient effects is provided in a separate (Part 2) continuation of this critical overview.
传统上，辅料在药物开发中是从其对药物溶解度、可制造性以及控制体外和体内药物释放的能力的角度来考虑的。这些影响主要通过涉及体外溶解方法的研究来评估。然而，人们越来越意识到，以前被认为是生物惰性的辅料可能会产生许多体内影响。这包括改变胃肠道 (GI) 转运时间、肠上皮细胞被动跨细胞或旁细胞通透性、主动转运活性或药物的预系统性代谢的潜力。在这篇关于辅料的生物效应的重要综述（第一部分）中，我们总结了一些选择发表的研究，这些研究探讨了这些各种体内因素。我们还包含一个表格，为读者指出已发表的综述，其中列出了一系列已知具有生物活性的辅料。在这篇综述的另一部分（第二部分）中，我们将讨论可用于探索这些辅料影响的体外、体内和计算方法。
