(443d) Synthesis and Stability Study of Polymorphic Transformed Mannitol/ LB Agar Microcarriers for Dry Powder Inhalation

Spray drying is a widely used technique for the preparation of drug carriers as it can provide easily control of particle size, powder density and morphology. However, spray-dried microparticles are often in an unstable state. Most of the spray-dried microparticles have not reached an equilibrium state due to the short spray-drying processing time. In our previous work, novel rough mannitol/LB Agar microparticles were successfully prepared by polymorphic transformation method. The mannitol/LB Agar microparticles when used as carriers for dry powder inhalation has shown good drug delivery performance. In this study, the stability of the fully-transformed and fully-crystallized mannitol/LB Agar microparticles is enhanced with the use of agar as a stabilizer. As-prepared microparticles were characterized by X-ray diffraction spectra (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA) and Andersen Cascade Impactor (ACI).

The X-ray diffraction spectra (XRD) results indicate that δ-mannitol was completely transformed to α-mannitol after immersing the spray-dried mannitol/LB Agar microparticles in hexane for a certain days. The scanning electron microscopy (SEM) shows that the spray-dried microparticles have smooth surface, while the roughness of the microparticle surface is increased after transformation. XRD indicates that the α-mannitol present in the transformed mannitol/LB Agar microparticles was stable for 33 months. SEM indicates that the small mannitol crystals in the transformed microparticles aggregated and self-assembled into nanorods. The transformed microparticles can maintain the rough-surface and spherical shape for 21 months. It is substantially longer than that of the microparticles without using agar as stabilizer, which can only maintain a stable shape for 6 months. Andersen Cascade Impactor (ACI) result shows that the fine particle fraction (FPF) of the model drug, Budesonide using the mannitol/LB Agar microparticles as drug carriers can also be maintained for 21-month.