Optimizing large porous mannitol-leucine microparticles via spray drying technique

Abstract

The development of large porous microparticles (LPPs) has gained attention for dry powder in-halation (DPI) formulations due to their potential to enhance the efficiency of drug delivery into the lungs. In this work, large porous mannitol-leucine microparticles (MALs) were developed using a spray drying technique. Mannitol was co-spray dried with ammonium bicarbonate (0–50 % w/w) and leucine (1–20 % w/w). The morphology of MAL particles was spherical hollow with corrugated surface. The MAL with 10 % leucine (MAL-10) showed the lowest bulk density (0.08 g/cm3) with the highest surface area (7.85 m2/g), while the aerodynamic diameter (Daer) was within 1–5 μm, indicating the suitability to penetrate the lung. The DSC and XRD results indicated that the MALs exhibited a mixture of β- and α-polymorphs, while the FT-IR spectra con-firmed that no chemical interaction during co-processing. The leucine co-processing significantly improved powder flowability of the MAL-10 (28.33° for angle of repose). In addition, the co-processing with high leucine concentration (10–20 %) significantly reduced moisture sorption, while the polymorph of MALs did not change after 30 days of hygroscopicity study that indicated good stability. According to all results, the MALs could potentially be applied as drug carriers for DPI formulations.