Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, USA.
Pharm Res. 2023 Jul;40(7):1633-1639. doi: 10.1007/s11095-023-03572-3. Epub 2023 Jul 31.
Subcutaneously administered drugs are growing in popularity for both large and small molecule drugs. However, development of these systems - particularly generics - is slowed due to a lack of formal guidance regarding preclinical testing and in vitro - in vivo correlations (IVIVC). Many of these methods, while appropriate for oral drugs, may not be optimized for the complex injection site physiologies, and release rate and absorption mechanisms of subcutaneous drugs. Current limitations for formulation design and IVIVC can be supported by implementing mechanistic, computational methods. These methods can help to inform drug development by identifying key drug and formulation attributes, and their effects on drug release rates. This perspective, therefore, addresses current guidelines in place for oral IVIVC development, how they may differ for subcutaneously administered compounds, and how modeling and simulation can be implemented to inform design of these products. As such, integration of modeling and simulation with current IVIVC systems can help in driving the development of subcutaneous injectables.
皮下给药在大分子和小分子药物中越来越受欢迎。然而，由于缺乏关于临床前测试和体外-体内相关性（IVIVC）的正式指导，这些系统的开发（特别是仿制药）进展缓慢。这些方法中的许多方法虽然适用于口服药物，但可能没有针对皮下药物的复杂注射部位生理学、释放率和吸收机制进行优化。通过实施机械、计算方法，可以为制剂设计和 IVIVC 的当前局限性提供支持。这些方法可以通过确定关键药物和制剂属性及其对药物释放速率的影响来帮助指导药物开发。因此，本文针对口服 IVIVC 开发的现行指南，讨论了它们对皮下给予化合物的可能差异，以及如何实施建模和模拟以告知这些产品的设计。因此，将建模和模拟与当前的 IVIVC 系统集成，可以帮助推动皮下注射剂的开发。
