Engineering Large Porous Mannitol-PVA Microparticles for Extended Drug Delivery via Spray Drying

Background: Large porous particles (LPPs) offer significant potential in drug delivery due to their porous structure and suitable particle size and shape, which can improve powder dispersibility and control drug release. Methods: In this study, sustained-release large porous microparticles of mannitol, PVA, and diclofenac sodium (MPDs) were developed using a spray drying technique. The influence of PVA co-spray drying and its concentration (0-40%) on the characteristics of the spray-dried particles was investigated. Results: Co-spray drying with PVA enhanced particle morphology, producing MPDs with a spherical shape and smooth surface, which minimized particle adhesion. This improvement correlated with a low Carr's Index value (17.56%), indicating favorable particle dispersibility and aerosol performance. The large geometric diameter (>5 μm) of the MPDs, coupled with their low bulk density (<0.1 g/cm³), suggested potential for inhalation use. FTIR, XRD, and DSC analyses revealed that PVA altered the polymorphic form of mannitol, with the MPDs exhibiting a mixture of the α and δ forms. In vitro dissolution tests demonstrated that PVA co-spray drying effectively prolonged drug release, with the formulation containing 40% PVA (MPD-4) showing an optimal release profile. The release kinetics followed first-order Higuchi models, suggesting drug release occurred through a matrix diffusion mechanism facilitated by the porous structure. Conclusions: These findings demonstrate the feasibility of engineering large porous microparticles with tailored release characteristics and physicochemical properties suitable for further development in inhalable or other controlled-release dosage forms.