Accelerated mass transfer from frozen thin films during thin-film freeze-drying

Abstract

Freeze-drying, or lyophilization, is widely used to produce pharmaceutical solids from temperature-sensitive materials but the process is time and energy inefficient. Herein, using E. coli as a model live organism, whose viability in dry powders is highly sensitive to the water content in the powders, we demonstrated that the drying rate of thin-film freeze-drying (TFFD) is significantly higher than that of the conventional shelf freeze-drying, likely because the large total surface area from the loosely stacked frozen thin films and the low thickness of the thin films enable faster and more efficient mass transfer during freeze-drying. The highly porous nature and high specific surface area of the thin-film freeze-dried powders may have contributed to the faster mass transfer as well. Moreover, we demonstrated that TFFD can be applied to produce dry powders of E. coli and L. acidophilus with minimum bacterial viability loss (i.e., within one log reduction), and the L. acidophilus dry powder is suitable for intranasal delivery. It is concluded that TFFD technology is promising in addressing the time- and cost-inefficient issue of conventional shelf freeze-drying.

Feasibility of intranasal delivery of thin-film freeze-dried, mucoadhesive AS01B-adjuvanted vaccine powders

“…Besides the AS01 B -adjuvanted vaccines, the TFF technology has been successfully applied to various other types of vaccines, including vaccines adjuvanted with aluminum salt (Alzhrani et al, 2021; Li et al, 2015; Thakkar et al, 2018), MF59 or AddaVax (AboulFotouh et al, 2022a), plasmid DNA vaccine (Xu et al, 2022), viral vector-based vaccines (Cui, unpublished data), and messenger RNA-lipid nanoparticle vaccines (Cui, unpublished data). In addition, both Gram-positive and Gram-negative bacteria in suspension can be converted to dry powders using the TFF technology (Wang et al, 2022). Therefore, it is expected that various other types of vaccines can be administered intranasally as TFF powders using the UDSP nasal device to target the vaccines to the lymphoid tissues in the nasopharynx region in humans.…”

Progress on Thin Film Freezing Technology for Dry Powder Inhalation Formulations

“…Biologics and vaccines that have undergone TFF conversion can be transported at room temperature and reconstituted at the site of administration, doing away with the need for a cold chain. TFF technology is useful in the creation of biologics and vaccines, as well as medications for indications other than lung disorders, in animal models, and in vitro testing [18]. An in vivo absorption study evaluating the TFF-treated powder with brand-name Sporanox ® was then carried out.…”