Mechanistic modeling of intramuscular administration of long-acting injectable suspensions accounting for fibrosis at the depot site

Conference: AAPS
Software: GastroPlus®
Division: Simulations Plus


  • Antipsychotic drugs formulated as long-acting injectables (LAIs) significantly improve patient compliance compared to regimens that require daily oral administration1. However, the clinical development of LAIs has proven challenging due to limited understanding of the tissue response to injected particles (e.g., inflammation, fibrosis formation) impacting in vivo performance.
  • Physiologically-based pharmacokinetic (PBPK) models could be valuable in establishing a link between in vitro formulation characteristics and in vivo performance while incorporating formulation interactions with the physiology at the injection site.
  • The purpose of this study was to use PBPK modeling to delineate the in vivo performance of an LAI suspension, informed by in vitro data, and accounting for physiological responses at the injection site in humans.
  • Aripiprazole (AR), formulated as prodrug AR-lauroxil (AR-L) for LAI, was used as a model drug.

By Daniela Amaral Silva, Nilesh Malavia, Diane J. Burgess, Alam Khondoker, Yan Wang, Viera Lukacova

AAPS 2023 PharmSci 360,Orlando, FL, October 22-25, 2023