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

Abstract

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 (D 50 ) 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.

Drug-Facilitated Crystallization of Spray-Dried CD-MOFs with Tunable Morphology, Porosity, And Dissolution Profile

“…Highly crystalline spray-dried CD-MOF particles were formed at certain incubation times, such as 6 and 48 h. As the CD-MOF crystals are more physically stable than the corresponding amorphous material, CD-MOF crystal seeds grew continuously in an antisolvent-rich environment with a concentrated solute. In our previous study, amorphous and crystalline spray-dried CD-MOFs were successfully synthesized using a precursor in the presence of either water or ethanol as solvents . A similar phenomenon was observed using other MOF materials and several organic solvents …”

“…Vapor diffusion is a conventional method used for preparing CD-MOF crystals. − Although highly porous CD-MOF crystals can be synthesized using this method, it is time-consuming, sensitive, and not suitable for manufacturing. Therefore, a spray-drying method has been proposed to overcome the issues with the vapor diffusion method . Spray drying is a well-known approach for designing functional particles. , Compared with the vapor diffusion method, CD-MOF powders obtained by spray drying have several advantages, such as a higher product yield, shorter synthesis time, and tunable particle properties.…”

“…In our previous report, 19 we established the synthesis of CD-MOF using spray-drying, and we also compared spray-drying to vapor diffusion and poor solvent crystallization method. The spray-dried CD-MOF showed characteristic particle morphology, size, and surface area, along with an outstanding aerosol dispersion performance.…”

“…Therefore, a spray-drying method has been proposed to overcome the issues with the vapor diffusion method. 19 Spray drying is a well-known approach for designing functional particles. 20,21 Compared with the vapor diffusion method, CD-MOF powders obtained by spray drying have several advantages, such as a higher product yield, shorter synthesis time, and tunable particle properties.…”

Transformation behaviour of salts composed of calcium ions and phosphate esters with different linear alkyl chain structures in a simulated body fluid modified with alkaline phosphatase

“…However, we consider that learning from organic chemistry and polymer chemistry is worthwhile, and is a shorter way to design and develop highly functional ceramic biomaterials. Functional metal-organic frameworks [ 19–23 ], sol-gel derived inorganic-organic hybrid materials [ 24–28 ] and organically modified inorganic layered compounds [ 29–33 ] are typical examples of this. If we can not only partially incorporate organic components into ceramics as in these cases, but also incorporate highly designed polymeric materials, then this would enable the design of even more functional ceramic biomaterials.…”