Associate Professor Graz University of Technology Graz, Steiermark, Austria
Excipient plays a critical role in the stabilization of protein drugs during and following the formulation processing, including drying to form solid products. Saccharides are stabilizers in freeze-drying and spray-drying (SD) of biopharmaceutical formulations. We employed a miniaturized sessile single droplet drying of different aqueous saccharide-protein systems, and the findings were compared with SD. The protein drugs include trypsin, catalase, and a model protein X. Trehalose, dextran, and Hydroxypropyl β-cyclodextrin (HPβCD) were used as the excipients. The molecular dynamics simulations were performed for understanding the stabilization mechanisms. HPβCD showed a tendency to self-assemble and binds to some sites of trypsin to drag the air-water interfaces promoting aggregation during drying. The effect of drying rates and saccharide types on peroxide formation via the degradation of polysorbate was also investigated. The results highlight the need for careful consideration when selecting saccharides and their ratios.
Learning Objectives:
Comparison of trehalose, cyclodextrin, and dextran for the particle engineering of protein drugs formulations via spray drying
The importance of small-scale screening via sessile droplet drying of the formulation candidates and relevance for selection of formulations for spray drying
Application of molecular docking and molecular modeling to support the finding of excipient´s effect of protein stability during evaporative drying
The role of saccharide excipients on the polysorbate autoxidation during evaporative drying of single droplet and spray drying