Population Balance Modeling of Aggregation in Long-Acting Injectable Formulations Integrated with PBPK Modeling

Authors: Mullin JM, Amaral Silva D, Alam K, Al Shoyaib A
Conference: AAPS
Keywords: AAPS 2025, gastroplus, in vivo, long-acting injectable formulations, PBPK modeling, population balance model (PBM)
Software: GastroPlus®

Purpose 

  • Long-acting injectable (LAI) formulations are criticaI for sustained drug delivery in a multitude of applications for birth control, psychological disorders, human immunodeficiency virus (HIV), and cancer.
  • The injection depot site is a complex system due to:
    • Immune response
    • Low compound solubility
    • Particle agglomeration/size
    • Viscosity
    • Injection volume
    • Excipient effects
  • Simulating agglomeration dynamics is essential for understanding the difficult-to-observe in vivo formulation behavior at the injection site1.
  • The objective of this study is to develop a population balance model (PBM) to describe in vivo agglomeration of once-monthly extended-release LAI suspension of lnvega Sustenna•, paliperidone palmitate (PP), and integrate it with a physiologically based pharmacokinetic   (PBPK) model to predict the in vivo performance.

By James M. Mullin, Daniela Silva, Khondoker Alam, Abdullah Al Shoyaib

American Association of Pharmaceutical Scientists (AAPS) PharmSci360, November 9-12, 2025, San Antonio, TX