Vlachou Marilena, Karalis Vangelis
Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece.
Materials (Basel). 2021 Jan 24;14(3):555. doi: 10.3390/ma14030555.
The aim of this study was to develop a new in vitro-in vivo simulation (IVIVS) approach in order to predict the outcome of a bioequivalence study. The predictability of the IVIVS procedure was evaluated through its application in the development process of a new generic product of amlodipine/irbesartan/hydrochlorothiazide. The developed IVIVS methodology is composed of three parts: (a) mathematical description of in vitro dissolution profiles, (b) mathematical description of in vivo kinetics, and (c) development of joint in vitro-in vivo simulations. The entire programming was done in MATLAB and all created scripts were validated through other software. The IVIVS approach can be implemented for any number of subjects, clinical design, variability and can be repeated for thousands of times using Monte Carlo techniques. The probability of success of each scenario is recorded and finally, an overall assessment is made in order to select the most suitable batch. Alternatively, if the IVIVS shows reduced probability of BE success, the R&D department is advised to reformulate the product. In this study, the IVIVS approach predicted successfully the BE outcome of the three drugs. During the development of generics, the IVIVS approach can save time and expenses.
本研究的目的是开发一种新的体外-体内模拟（IVIVS）方法，以预测生物等效性研究的结果。通过将IVIVS程序应用于氨氯地平/厄贝沙坦/氢氯噻嗪新仿制药的开发过程，评估了该程序的可预测性。所开发的IVIVS方法由三个部分组成：（a）体外溶出曲线的数学描述，（b）体内动力学的数学描述，以及（c）联合体外-体内模拟的开发。整个编程在MATLAB中完成，所有创建的脚本都通过其他软件进行了验证。IVIVS方法可针对任何数量的受试者、临床设计、变异性进行实施，并可使用蒙特卡罗技术重复数千次。记录每种情况成功的概率，最后进行总体评估，以选择最合适的批次。或者，如果IVIVS显示生物等效性成功的概率降低，建议研发部门重新制定产品配方。在本研究中，IVIVS方法成功预测了三种药物的生物等效性结果。在仿制药开发过程中，IVIVS方法可以节省时间和费用。
