Crystalline Rearranged CD-MOF Particles Obtained via Spray-Drying Synthesis Applied to Inhalable Formulations with High Drug Loading

γ-Cyclodextrin-based metal–organic framework (CD-MOF) particles were prepared using poor solvent crystallization and spray-drying methods in order to advance conventional engineering processes. Particles were characterized in terms of their morphology, size, surface area, surface elemental composition, crystallinity, and drug content. CD-MOFs prepared by the poor solvent crystallization method exhibit similar morphologies and crystallinities to those fabricated by vapor diffusion. In contrast to the development of the (γ-CD)6 cubic array, the rapid evaporation of the solvent during spray-drying promoted the formation of hollow CD-MOF particles with low crystallinity. The CD-MOF structure in spray-dried particles reformed into the well-known (γ-CD)6 cubic array following contact with ethanol. In terms of their spherical shape, low density, and geometric median particle size (D50) that is lower than 5 μm, the potential application of spray-dried CD-MOF for dry powder inhaler formulation was affirmed. Thus, the spray-drying process was further enhanced using a modified procedure. Modified spray-dried particles achieved an outstanding aerosolization performance by initiating crystal growth using an ethanolic spray-drying precursor. The successful design of this crystal structure grants CD-MOF products a high potential for use in inhalable formulation carriers and likely for other applications in the future.