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Tracking Solid State Dynamics in Spray-Dried Protein Powders at Infrared and Terahertz Frequencies

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Shmool, Talia A 
Batens, Maarten 
Massant, Jan 
Van den Mooter, Guy 
Axel Zeitler, J 

Abstract

Therapeutic protein powders can be prepared by spray-drying. This process is known to result in solid particles of relatively narrow size distribution and high yield and purity [1], [2]. Additionally, the spray-drying process is rapid, semi-continuous, cost-effective, reproducible and scalable. The process transforms a liquid into dry particles by atomising the liquid feed in a hot drying gas stream [3]. One of the main advantages of spray-drying is that a wide range of formulations, including heat-sensitive materials, can be dried using this technique since the droplet surface will retain the wet-bulb temperature rather than the temperature of the hot drying gas, provided evaporation is taking place at the droplet surface. By the time the evaporation at the droplet/particle surface stops, the drying gas will already have cooled down, thus limiting the heat exposure of the formulation components to the relatively high inlet gas temperatures, and, in combination with the short process duration, making spray-drying a feasible process for heat-sensitive materials, including proteins [1], [2], [3]. While spray-drying is a well established process for small molecules, the additional challenge of ensuring protein stability of the dried product during storage currently limits its use for biopharmaceutical products [2], [4]. A major concern during the spray-drying process is the entire or partial unfolding of proteins due to their high susceptibility to migrate to the air-liquid interfaces where the surface energies can cause the protein to expose hydrophobic regions, resulting in facilitated protein-protein interactions and ultimately aggregation [5]. In order to prevent such undesired aggregation non-ionic surfactants, for example polysorbate, are often used to prevent accumulation of protein at the air-liquid interface, as these small and more mobile surfactants will preferentially position themselves at the interfaces [6]. To put more generally, the excipients of a formulation are vital in providing stability to the protein by maintaining its native conformation during the spray-drying process.

Description

Keywords

Bovine serum albumin, Dynamics, Infrared, Spray-dried protein powders, Terahertz, Biological Products, Chemistry, Pharmaceutical, Drug Compounding, Particle Size, Powder Diffraction, Powders, Protein Structure, Tertiary, Proteins

Journal Title

European Journal of Pharmaceutics and Biopharmaceutics

Conference Name

Journal ISSN

0939-6411
1873-3441

Volume Title

Publisher

Elsevier BV
Sponsorship
EPSRC (1198)
T.A.S. and J.A.Z. acknowledge funding from AstraZeneca UK Limited/MedImmune Limited and the UK Engineering and Physical Sciences Research Council (EP/N022769/1). T.A.S. would like to thank the AJA-Karten Trust and the AIA-Kenneth Lindsay Trust for their financial support.