Control of physical forms of drug particles for pulmonary delivery by spray drying and supercritical fluid processing

Dry powder inhalation (DPI) is an important means of pulmonary drug delivery for both local and systemic actions. Since drugs of different solid-state chemistry can influence a wide range of physical, chemical and biological properties, control of the solid-state structures and associated behaviours of drug particles is critical for DPI formulation. Current production technology of fine drug particles for pulmonary delivery utilizes sequential batch crystallization and micronization. However, this two-step manufacturing approach often causes unwanted crystallographic damage to the particles and may induce undesirable polymorphic transformation in certain materials. In recent years, spray-drying and supercritical fluid crystallization have emerged as two cost-efficient processing technologies that allow more precise control of the crystal forms and physical properties of the powders produced in a single step operation. This article presents a critical review of these latest technological developments in DPI formulation with focus on the regulation of the physical forms of inhaled drug particles.