The emerging role of physiologically based pharmacokinetic modelling in solid drug nanoparticle translation.

The use of solid drug nanoparticles (SDN) has become an established approach to improve drug delivery, supporting enhancement of oral absorption and long-acting administration strategies. A broad range of SDNs have been successfully utilised for multiple products and several development programmes are currently underway across different therapeutic areas. With some approaches, a large range of material space is available with diversity in physical characteristics, excipient choice and pharmacological behaviour. The selection of SDN lead candidates is a complex process including a broad range of in vitro and in vivo data, and a better understanding of how physical characteristics relate to performance is required. Physiologically-based pharmacokinetic (PBPK) modelling is based upon a comprehensive integration of experimental data into a mathematical description of drug distribution, allowing simulation of SDN pharmacokinetics that can be qualified in vivo prior to human prediction. This review aims to provide a description of how PBPK can find application into the development of SDN. Integration of predictive PBPK modelling into SDN development allows a better understanding of the SDN dose-response relationship, supporting a framework for rational optimisation while reducing the risk of failure in developing safe and effective nanomedicines.