Aungst B J
Du Pont Merck Pharmaceutical Company, Wilmington, DE 19880-0400.
J Pharm Sci. 1993 Oct;82(10):979-87.
The oral route is most preferred for chronic drug therapy. Poor oral bioavailability has the consequences of more variable and poorly controlled plasma concentrations and drug effects, in addition to possibly increased product cost. In this review, the most common causes of low oral bioavailability are categorized, and formulation strategies to improve bioavailability are summarized. Various methods that can be used to help identify the cause of low bioavailability are discussed. The focus of this article is on poor membrane permeation and presystemic degradation problems; solubility/dissolution rate problems are discussed only briefly. Poor membrane permeation and presystemic degradation problems are typically encountered in the efforts to develop oral proteins, peptides, and peptide mimics. Formulation strategies reviewed include the use of metabolism inhibitors, membrane permeation enhancers, ion pairing and complexation, and particulate carriers. Also reviewed are lipid and surfactant formulations, which have been shown to increase bioavailability by various mechanisms and which are only beginning to be understood and optimized.
口服途径是慢性药物治疗的首选。口服生物利用度差会导致血浆浓度和药物效应的变异性更大且控制不佳，此外还可能增加产品成本。在本综述中，对口服生物利用度低的最常见原因进行了分类，并总结了提高生物利用度的制剂策略。讨论了可用于帮助确定生物利用度低原因的各种方法。本文重点关注膜通透性差和系统前降解问题；溶解度/溶解速率问题仅作简要讨论。在开发口服蛋白质、肽和肽模拟物的过程中，通常会遇到膜通透性差和系统前降解问题。综述的制剂策略包括使用代谢抑制剂、膜渗透增强剂、离子对和络合作用以及微粒载体。还综述了脂质和表面活性剂制剂，它们已被证明可通过多种机制提高生物利用度，并且才刚刚开始被理解和优化。
