Comparison of melibiose and trehalose as stabilising excipients for spray-dried β-galactosidase formulations

Abstract

Spray-dried protein formulations commonly require stabilising excipients to prevent protein degradation during processing and storage, and trehalose has been commonly used. The purpose of this work was to evaluate melibiose in spray-dried protein formulations in comparison to trehalose. The protein-activity-preserving efficacy, process behaviour and storage stability were studied. Spray drying of β-galactosidase was carried out using different process temperature, drying air flow and feed liquid atomisation settings. Both melibiose and trehalose reduced protein activity loss during drying. A decrease in activities was observed when the process temperature exceeded a threshold temperature. During storage (30 days at 18% RH and 20 or 40 °C), the formulations dried below this threshold temperature showed no further activity loss, and the stabilising efficacy of the two disaccharides was equal. With higher process temperatures, the remaining protein activities after storage trended higher with melibiose formulations. All formulations remained amorphous. The powder yields of melibiose formulations were similar to trehalose. There was a difference in residual moisture contents, with melibiose formulations giving drier products. In conclusion, protein formulations with melibiose could be spray dried into amorphous powders that were physically stable, contained lower moisture contents and protected protein activity at least as well as trehalose formulations.

A Design of Experiment (DoE) approach to optimise spray drying process conditions for the production of trehalose/leucine formulations with application in pulmonary delivery

“…In fact, it has been well established that trehalose is known to be a superior stabilizer in providing protection to biological materials against dehydration and desiccation, in comparison with a number of other sugars, especially during lyophilization, spray drying and exposure to high temperatures in solution (Lipiainen et al, 2018;Rajagopal et al, 2013).…”

Development of an Orodispersible Film Containing Stabilized Influenza Vaccine

“…β-Galactosidase formulated with trehalose by freeze-drying was found to be the most stable formulation when compared with other sugars (i.e., dextran 70 kDa, dextran 6 kDa and inulin) [16]. In a study by Lipiäinen et al [29], melibiose or trehalose was used as stabilizing excipient for β-galactosidase by spray drying, and its activity remained for 30 days at 40 • C.…”

Progress in spray-drying of protein pharmaceuticals: Literature analysis of trends in formulation and process attributes

“…erythritol, glucosamine, and xylitol) were found only in one study each. [48,100,128] Even though mannitol is one of the most well-used sugars in commercialized biologic products, [141] when used alone to spray-dry certain classes of proteins (e.g. mAbs), its crystallization during processing has shown the potential to deleteriously affect product stability.…”

“…However, lactose and melibiose are reducing sugars, so their free aldehyde groups can undergo the Maillard reaction when in contact with the amino groups of proteins. [22,48,136] Although, the reducing disaccharides have been extensively selected to study protein spraydrying [17,22,24,44,48,51,80,81,83,84,86,94,111,128,131,144] and are used in some marketed bio-formulations, [141] it is crucial to guarantee that no detrimental chemical interaction takes place, during processing and storage. Within a spray-drying context, it has been reported that trehalose could be more successful than other sugars, when stabilizing proteins.…”