There is an immediate need to understand the critical formulation parameters that may affect product performance in vitro and in vivo, with a goal of developing IVIVCs for long-acting injectables. In this proposal, we will develop IVIVCs for a long-acting PLGA-based solid implant using a physiologically based pharmacokinetic (PBPK) modeling approach. PBPK modeling “provides a unique opportunity to understand how the physicochemical properties of drug molecules/polymer, implant specific properties, critical formulation attributes, and physiology, among other things, influence the in vivo release mechanisms of LAI drug products and their disposition characteristics. Successful execution of the project will entail (1) developing a bio-predictive in-vitro release testing method and determining how critical formulation and physicochemical properties impact the in-vitro release of PLGA-based buprenorphine implants; and (2) using a bottom-up PBPK approach to build IVIVCs that predict in-vivo PK profiles of PLGA-based buprenorphine implants from in-vitro data.