This article compares and explores vacuum foam-drying as an alternative drying technology to freeze-drying and spray drying for a recombinant human lipase as the model protein. Materials characteristics such as structure, surface composition and the solid-state properties of the dry materials were compared and investigated. Moreover, the technical functionality in terms of reconstitution characteristics and the lipase stability were also investigated. The stability of the lipase was evaluated through activity measurements. Sucrose and dextran D40 (40 kDa) were used as matrix former and the surfactant α-dodecyl maltoside was used as surface active additive. The study demonstrated that the drying technique greatly influenced the material structure and composition which in turn affected the reconstitution characteristics. The lipase was overrepresented at the material surface in declining order spray-dried > vacuum foam-dried > freeze-dried. The lipase activity was retained up to 10 % lipase content in solids, but at 20 % lipase a loss of activity was observed for all drying techniques. Phase separation in the solid material may be an explanation. Vacuum foam-drying shows promise as an alternative drying technique for the lipase, and potentially other proteins. 

This paper explores how vacuum foam-drying of a protein is influenced by formulation parameters by investigating the foam structure, physical properties of the foam, and the stability of the protein. Recombinant human bile salt-stimulated lipase was used as a model of a protein drug. The stability of the lipase was evaluated through activity measurements. Two disaccharides (sucrose and trehalose), strongly tending to an amorphous form, were used as matrix formers, and the physical properties were assessed through residual water content, glass transition temperature, and crystalline state. Moreover, some formulations included surfactants with different sizes and structures of the head group. The alkyl chain length was kept constant to only investigate the impact of the surfactant head group, in the presence of the lipase, on the foamability and surface coverage of the lipase. The study demonstrated that the lipase allowed for a dry, solid foam with a foam overrun of up to 2600 %. The wall thickness of the dry, solid foam was estimated to be 20–50 µm. Clear differences between sucrose and trehalose as matrix former were identified. The lipase showed no tendency to lose activity because of the drying and rehydration, despite a proportion of the lipase covering the surfaces of the dry material. 

Solid-state properties of dried protein formulations are important for stability and functionality of the product. This study investigates how different drying technologies (freeze-drying with and without annealing, spray drying and spray-freeze drying) affect the structure and solid-state properties of a set of matrix formulations composed of trehalose (glass former) and mannitol (scaffolding agent) in five ratios. The dried materials were characterized using differential scanning calorimetry, thermogravimetric analysis, x-ray diffraction and scanning electron microscopy. The morphology of the dried matrix is determined by the drying technology and the composition. In all mixtures, mannitol partially dissolved in the amorphous trehalose, resulting in reduced glass transition temperature. At least 50% mannitol is required to achieve a scaffolding effect through crystallized mannitol. At 25% mannitol poor structural stability is obtained regardless of drying technology. Despite the vast differences in drying kinetics, all drying technologies resulted in similar amorphous content in the dried material. © 2022 The Author(s).