Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, UAE.
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia.
Drug Dev Res. 2018 May;79(3):97-110. doi: 10.1002/ddr.21427. Epub 2018 Apr 26.
Preclinical Research & Development An in vitro-in vivo correlation (IVIVC) is as a predictive mathematical model that demonstrates a key role in the development, advancement, evaluation and optimization of extended release, modified release and immediate release pharmaceutical formulations. A validated IVIVC model can serve as a surrogate for bioequivalence studies and subsequently save time, effort and expenditure during pharmaceutical product development. This review discusses about different levels of correlations, general approaches to develop an IVIVC by mathematical modelling, validation, data analysis and various applications. In the current setting, the dearth of success associated with IVIVC is due to complexity of underlying scientific principles as well as the practice of fitting/matching in vivo plasma level-time data with in vitro dissolution profile. Hence, a simple, straightforward practical means to predict plasma drug levels by convolution technique and percentage drug absorbed computed from in vitro dissolution profile based on deconvolution method are illustrated. The bioavailability/bioequivalence assessment and evaluation are frequently validated by the pharmacokinetic parameters such as maximum concentration, time to reach maximum concentration, and area under the curve. The implementation of a quality by design manufacturing based on in vivo bioavailability and clinically relevant dissolution specification are recommended because corresponding design safe space will guarantee that all batches from relevant products are met with sufficient quality and bioperformance. Recently, United States Food and Drug Administration and European Medicines Agency have proposed that in silico/physiologically based pharmacokinetic modelling can be used in decision making during preclinical experiments as well as to recognize the dissolution profiles that can forecast and ensure the desired clinical performance.
临床前研究与开发
体外-体内相关性 (IVIVC) 是一种预测性的数学模型，在开发、推进、评估和优化缓释、改良释放和速释药物制剂方面发挥着关键作用。验证的 IVIVC 模型可用作生物等效性研究的替代方法，从而在药物产品开发过程中节省时间、精力和开支。本文综述了不同水平的相关性、通过数学建模、验证、数据分析和各种应用开发 IVIVC 的一般方法。在当前情况下，IVIVC 缺乏成功的原因是由于基础科学原理的复杂性以及将体内血浆水平-时间数据与体外溶解曲线拟合/匹配的实践。因此，本文介绍了一种简单、直接的实用方法，即通过卷积技术预测血浆药物水平，并根据解卷积方法从体外溶解曲线计算吸收的药物百分比。生物利用度/生物等效性评估和评价通常通过药代动力学参数（如最大浓度、达到最大浓度的时间和曲线下面积）进行验证。建议基于体内生物利用度和临床相关溶解规范实施基于质量的设计制造，因为相应的设计安全空间将保证相关产品的所有批次都具有足够的质量和生物性能。最近，美国食品和药物管理局和欧洲药品管理局提出，基于计算机/生理的药代动力学模型可用于临床前实验中的决策制定，以及识别可预测和确保所需临床性能的溶解曲线。
