Pharmaceutical dry powders of small molecules prepared by thin-film freezing and their applications – A focus on the physical and aerosol properties of the powders

[Display omitted] •Thin-film freezing technology can be applied to produce pharmaceutical powders of small molecule drugs.•The powders exhibit unique morphology, high surface area, and brittle fracture.•The brittle-matrix powders contain loosely connected micro- and/or nano-particles.•Powders prepared using TFF technology generally have desirable aerosol properties for pulmonary delivery by oral inhalation.•TFF powders of poorly water soluble drugs generally have improved dissolution profiles and increased oral bioavailability. Thin-film freeze-drying is a dry powder engineering technology that involves in a rapid thin-film freezing (TFF) process followed by lyophilization to remove solvent. TFF process has been successfully used to produce pharmaceutical powders of the small and large molecule drugs as well as live organisms. This paper provides a comprehensive review of the pharmaceutical applications of TFF powders of small molecule drugs intended for pulmonary delivery or oral administration. The powders produced by the TFF process often exhibited unique physical properties such as amorphous morphology, high porosity, brittle matrix structure, and high specific surface area, and the powders also often contain loosely connected micron or submicron particles or aggregates. The TFF process parameters and formulation compositions directly affect the physical properties of the powders. These physical properties render TFF powders desirable aerodynamic properties for efficient pulmonary delivery by oral inhalation and help enhance the dissolution of poorly water-soluble small molecule drugs in the powders and thus improve their bioavailability after oral administration.