Dissolution Testing for Inhaled Nanoparticulate Drug Delivery Systems

The dissolution of inhaled nanoparticles plays a critical role in determining the therapeutic efficacy and bioavailability of pulmonary drug delivery systems. Unlike traditional oral formulations, inhaled drugs encounter unique physiological environments—characterized by minimal fluid volume, rapid clearance mechanisms, and complex lung morphology—that significantly affect dissolution behavior. This approach has been recently explored for the administration of advanced formulations that aim at further improving the efficacy and expanding the range of drugs administered via this route. This chapter explores different in vitro dissolution techniques employed for nanoparticulate formulations, since these systems are increasingly used for the treatment of respiratory diseases like asthma, COPD, infections or even systemic diseases via pulmonary absorption. Here, the limitations of conventional dissolution methods (e.g., paddle and flow-through cell) in replicating lung conditions are discussed and are presented with emerging biorelevant dissolution approaches which better simulate the air–liquid interface conditions in lung fluids, such as Transwell, Franz cells, Dissolvit and Respicell. The chapter presents the dissolution of several paradigmatic advanced formulations, including nanosuspensions, liposomes, nanocrystals, and composite microparticles, illustrating their dissolution properties and the impact of the formulation on it. Emphasis is placed on highlighting the capacity of different dissolution methods to discriminate different formulation dissolution profiles. Finally, regulatory perspectives and the role of dissolution testing in establishing in vitro–in vivo correlations (IVIVC) are briefly addressed, underscoring the need for standardized, physiologically relevant methods to support the development and approval of innovative inhaled nanomedicines.