Emerging techniques for modeling and simulating subcutaneous injection and fate of drugs after injection

Subcutaneous (SC) administration offers multiple advantages over intravenous (IV) administration across different therapeutic areas and chemical modalities. Despite progress, some knowledge gaps persist in understanding the SC injection process, drug fate within the SC site, and SC absorption and bioavailability. This review provides an overview of emerging modeling and simulation techniques to tackle these knowledge gaps. Various in silico mechanistic models have been used to simulate SC injection dynamics, injection depot geometry, tissue backpressure, tissue deformation, changes in tissue porosity and permeability, drug migration within the SC site, and drug absorption. On the other hand, in vitro models and methods have advanced to emulate in vivo SC tissue, assess critical quality attributes of SC drug products, and establish in vitro-in vivo correlations. Additionally, this review discussed predictive methods for mAb SC bioavailability. Advances in modeling and simulation techniques can accelerate the development of SC drug products.