Li Shoufeng, He Handan, Parthiban Lakshman J, Yin Hequn, Serajuddin Abu T M
Pharmaceutical Development Section, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA.
J Pharm Sci. 2005 Jul;94(7):1396-417. doi: 10.1002/jps.20378.
Predictive scientific principles and methods to assess in vivo performance of pharmaceutical dosage forms based on in vitro studies are important in order to minimize costly animal and human experiments during drug development. Because of issues related to poor solubility and low permeability of newer drug candidates, there has in recent years been a special focus on in vitro-in vivo correlation (IV-IVC) of drug products, particularly those used orally. Various physicochemical, biopharmaceutical, and physiological factors that need to be considered in successful IV-IVC of immediate-release oral dosage forms are reviewed in this article. The physicochemical factors include drug solubility in water and physiologically relevant aqueous media, pK(a) and drug ionization characteristics, salt formation, drug diffusion-layer pH, particle size, polymorphism of drug substance, and so forth. The biopharmaceutical factors that need to be considered include effects of drug ionization, partition coefficient, polar surface area, etc., on drug permeability, and some of the physiological factors are gastrointestinal (GI) content, GI pH, GI transit time, etc. Various in silico, in vitro, and in vivo methods of estimating drug permeability and absorption are discussed. Additionally, how IV-IVC may be applied to immediate-release oral dosage form design are presented.
基于体外研究评估药物剂型体内性能的预测性科学原理和方法对于在药物开发过程中尽量减少昂贵的动物和人体实验非常重要。由于新型候选药物存在溶解度差和渗透性低等问题，近年来特别关注药物产品的体外-体内相关性（IV-IVC），尤其是口服制剂。本文综述了速释口服剂型成功实现IV-IVC时需要考虑的各种物理化学、生物药剂学和生理学因素。物理化学因素包括药物在水和生理相关水性介质中的溶解度、pK(a)和药物电离特性、盐的形成、药物扩散层pH值、粒径、药物多晶型等。需要考虑的生物药剂学因素包括药物电离、分配系数、极性表面积等对药物渗透性的影响，一些生理学因素包括胃肠道（GI）内容物、GI pH值、GI转运时间等。讨论了各种预测药物渗透性和吸收的计算机模拟、体外和体内方法。此外，还介绍了IV-IVC如何应用于速释口服剂型设计。
