Mechanistic understanding of drug release in dissolution apparatuses - In-depth review

Dissolution apparatuses are indispensable tools in the pharmaceutical industry for evaluating drug release from dosage forms under standardized conditions. They support formulation development, quality control, and regulatory compliance. Despite their widespread use, dissolution testing often yields variable results, often due to differences in hydrodynamic conditions within the dissolution apparatus. The hydrodynamic is influenced by several factors, including apparatus geometry, formulation properties, medium composition, and operating parameters. Variability in dissolution testing can lead to serious consequences, including product recalls, costly investigations, and regulatory delays. Therefore, a mechanistic understanding of these factors is critical for developing physiologically relevant and reliable dissolution methods. Experimental techniques and computational modeling have been employed to characterize flow behavior and drug release mechanisms. However, their predictive capabilities remain constrained by simplifying assumptions and the complexity of dissolution processes. Additionally, dissolution data are used to establish in vitro-in vivo correlations (IVIVCs) and support biowaivers in bioequivalence studies. However, the development of robust IVIVCs is often limited by the availability of insufficient or poor-quality datasets. This review provides an overview of current experimental and computational approaches to understanding drug release in dissolution apparatuses, highlighting key challenges in method development and modeling that must be addressed to ensure reliable and clinically relevant outcomes.