Role of Modeling and Simulation in Preclinical and Clinical Long-Acting Injectable Drug Development.

Innovations in the field of long-acting injectable drug development are increasingly being reported. More advanced in vitro and in vivo characterization can improve our understanding of the injection space and aid in describing the long-acting injectable (LAI) drug's behavior at the injection site more mechanistically. These innovations may enable unlocking the potential of employing a model-based framework in the LAI preclinical and clinical space. This review provides a brief overview of the LAI development process before delving deeper into the current status of modeling and simulation approaches in characterizing the preclinical and clinical LAI pharmacokinetics, focused on aqueous crystalline suspensions. A closer look is provided on in vitro release methods, available biopharmaceutical models and reported in vitro/in vivo correlations (IVIVCs) that may advance LAI drug development. The overview allows identifying the opportunities for use of model-informed drug development approaches and potential gaps where further research may be most warranted. Continued investment in improving our understanding of LAI PK across species through translational approaches may facilitate the future development of LAI drug products.