KONA Powder and Particle Journal
Online ISSN : 2187-5537
Print ISSN : 0288-4534
ISSN-L : 0288-4534
Review Papers
The Development of Thin-Film Freezing and Its Application to Improve Delivery of Biologics as Dry Powder Aerosols
Stephanie HufnagelSawittree SahakijpijarnChaeho MoonZhengrong CuiRobert O. Williams III
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2022 Volume 39 Pages 176-192


While the formulation of pharmaceuticals as liquids is common practice, powders are associated with enhanced stability, avoidance of the cold chain, lower dosing requirements, and more convenient administration. These are particularly critical for proteins, as they are expensive and complicated to manufacture. Powders also have improved aerosol properties for pulmonary delivery. Conventional techniques for formulating powders include spray-drying, shelf freeze-drying, spray freeze-drying, and spray freezing into liquid, but they produce powders with poor aerosol performance and/or activity due to suboptimal powder properties. Thin-film freezing (TFF) is a new cryogenic technique that can engineer highly porous, brittle, powder matrices with excellent aerosol performance properties and stability. Herein, we describe TFF in comparison to other cryogenic techniques. Physical properties of TFF powders such as morphology, moisture sorption, stability, solubility, and dissolution, as well as aerosol properties are discussed. In addition, factors that significantly affect the physical and aerosol properties of dry powders prepared by TFF, such as solids content, drug loading, solvent system, excipient, and dry powder delivery device, are analyzed. Finally, we provide evidence supporting the applicability of using TFF to prepare dry powder formulations of protein-based pharmaceuticals, enabling their cold chain-free storage as well as efficient pulmonary delivery.

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