Advanced Dissolution Testing for Novel Drug Formulations: Challenges, Emerging Methods, and Regulatory Perspectives

Advanced drug delivery systems (ADDS), such as nanoparticles, liposomes, and stimuli-responsive formulations, offer enhanced therapeutic outcomes through controlled and targeted drug release. However, these innovative systems present significant challenges to traditional in vitro dissolution testing methods. Classical dissolution techniques, such as USP I and II, are often insufficient for capturing the complex release behaviors of modern formulations, which differ from conventional drug forms. This review explores the limitations of traditional dissolution tests and examines emerging strategies to address these challenges. These include modifications to dissolution apparatus, such as flow-through cells, microfluidic systems, and dialysis methods, alongside advanced analytical tools like real-time spectroscopic monitoring and imaging techniques. The integration of physiologically based pharmacokinetic (PBPK) modeling and Quality-by-Design (QbD) principles is discussed as a pathway to enhance in vitro–in vivo correlation (IVIVC). Additionally, the review considers regulatory perspectives from agencies such as the FDA, EMA, and ICH, highlighting the increasing acceptance of novel testing approaches, including in silico modeling and Process Analytical Technology (PAT). By adapting dissolution testing methods to the specific characteristics of novel drug delivery systems, both researchers and regulators can ensure reliable drug release evaluations, safeguarding therapeutic efficacy and patient safety.