Department of Engineering, Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University , Elche, Spain.
Expert Opin Drug Deliv. 2020 Jun;17(6):791-803. doi: 10.1080/17425247.2020.1750593. Epub 2020 Apr 20.
Controlled release (CR) dosage forms comprise a wide range of technologies, which modify the drug pharmacokinetic (PK) profile by avoiding the immediate release (IR) of the active pharmaceutical ingredient (API). They are particularly of interest in chronic diseases, for narrow therapeutic index drugs or for targeting a particular gastrointestinal tract (GI) segment.
Diffusion and dissolution limited controlled release systems are described in terms of release kinetics and formulation strategies with e xamples marketed or under development. Additionally, the physiological variables affecting the release (such as fluid pH, volume and composition, physical forces, and transit times) and the in vitro dissolution techniques currently available are reviewed.
Selection of the appropriate release mechanism is not a straightforward process, as it requires a balance based on the desired target, the API properties and the technological challenges of the dosage form structure. Diffusion, dissolution or a combination of both could be adequate without an absolute superiority of one mechanism over the other. The combination of in vivo predictive dissolution systems, with mathematical modeling of the release mechanism and its correlation with formulation composition could help to design prototype candidates, with enhanced probabilities of success in human clinical trials.
控释（CR）剂型包含了广泛的技术，通过避免活性药物成分（API）的即刻释放来改变药物的药代动力学（PK）特征。它们在慢性病、治疗指数较窄的药物或靶向特定胃肠道（GI）段的情况下特别有用。
本文介绍了扩散和溶解限制型控释系统，包括释放动力学和制剂策略，并举例说明了已上市或正在开发的产品。此外，还回顾了影响释放的生理变量（如流体 pH 值、体积和成分、物理作用力和通过时间）以及目前可获得的体外溶解技术。
选择合适的释放机制并不是一个简单的过程，因为它需要在目标、API 性质和剂型结构的技术挑战之间取得平衡。扩散、溶解或两者的结合都可能是足够的，而且一种机制并不一定优于另一种机制。体内预测性溶解系统与释放机制的数学模型及其与配方组成的相关性相结合，有助于设计原型候选物，从而提高在人体临床试验中成功的概率。
