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

<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results</b>: 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. <b>Conclusions</b>: 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.