Establishment of preclinical mechanistic in vitro-in vivo correlations for long-acting injectable suspensions​

Authors: Amaral Silva D, Bao Q, Wan B, Malavia N, Burgess DJ, Lukacova V
Conference: AAPS
Keywords: AAPS 2022, in vitro-in vivo correlations, long-acting injectable formulations, PBPK modeling
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

Purpose

Long acting injectable (LAI) formulations administered through subcutaneous (SC) or intramuscular (IM) routes provide sustained drug release over an extended period. For LAIs formulated as crystalline suspensions, the extended release is obtained through the formation of an in-situ drug depot at the injection site from which poorly soluble drugs slowly dissolve and are subsequently absorbed into the systemic circulation1. ​

The development of complex generic LAIs is challenging since the relationship between solubility, particle size, and in vivo release from a parenteral suspension has not yet been established systematically. In this scenario, the use of modeling and simulation may provide a unique opportunity to mechanistically understand the in vivo release of drug from LAI suspensions and drug disposition. Establishing mechanistic in vitro–in vivo correlations (IVIVCs) is a valuable approach to further drug product development of LAIs. 

By Daniela Amaral Silva, Quanying Bao, Bo Wan, Nilesh Malavia, Diane J. Burgess, Viera Lukacova

Presented at American Association of Pharmaceutical Scientists (AAPS) Pharm Sci 360 Boston, Massachusetts October 16-19, 2022​