ABSTRACT

Introduction

Excipients are necessary to develop oral dosage forms of any Active Pharmaceutical Ingredient (API). Traditionally, excipients have been considered inactive and inert substances, but, over the years, numerous studies have contradicted this belief. This review focuses on the effect of excipients on the physiological variables affecting oral absorption along the different segments of the gastrointestinal tract. The effect of excipients on the segmental absorption variables are illustrated with examples to help understand the complexity of predicting their in vivo effects.

Areas covered

The effects of excipients on disintegration, solubility and dissolution, transit time, and absorption are analyzed in the context of the different gastrointestinal segments and the physiological factors affecting release and membrane permeation. The experimental techniques used to study excipient effects and their human predictive ability are reviewed.

Expert opinion

The observed effects of excipient in oral absorption process have been characterized in the past, mainly in vitro (i.e. in dissolution studies, in vitro cell culture methods or in situ animal studies). Unfortunately, a clear link with their effects in vivo, i.e. their impact on Cmax or AUC, which need a mechanistic approach is still missing. The information compiled in this review leads to the conclusion that the effect of excipients in API oral absorption and bioavailability is undeniable and shows the need of implementing standardized and reproducible preclinical tools coupled with mechanistic and predictive physiological-based models to improve the current empirical retrospective approach.

中文翻译：

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不同胃肠段辅料对口服吸收过程的影响

摘要

介绍

赋形剂是开发任何活性药物成分 (API) 的口服剂型所必需的。传统上，赋形剂被认为是非活性和惰性物质，但多年来，许多研究与这一信念相矛盾。本综述重点关注赋形剂对影响胃肠道不同部分口服吸收的生理变量的影响。赋形剂对分段吸收变量的影响通过实例加以说明，以帮助理解预测其体内效应的复杂性。

覆盖区域

在不同胃肠段和影响释放和膜渗透的生理因素的背景下，分析了赋形剂对崩解、溶解度和溶出度、转运时间和吸收的影响。回顾了用于研究赋形剂效果及其人类预测能力的实验技术。

专家意见

赋形剂在口服吸收过程中观察到的影响在过去主要是在体外（即在溶出研究、体外细胞培养方法或原位动物研究中）表征的。不幸的是，仍然缺少与它们的体内效应的明确联系，即它们对 Cmax 或 AUC 的影响，这需要机械方法。本综述中汇编的信息得出的结论是，辅料对 API 口服吸收和生物利用度的影响是不可否认的，并表明需要实施标准化和可重复的临床前工具，并结合基于机械和预测生理的模型来改进当前的实证回顾性方法.