Improving protein stabilization by spray drying: formulation and process development

There is an increasing interest for dried protein formulations in pharmacy. They may offer several advantages over aqueous formulations, such as ease of storage, longer shelf life, and use for solid dosage forms. However, the mechanisms underlying stabilization in the solid state are not yet fully understood.
Proteins in their solid state can be stabilized by incorporating them into a matrix of sugar molecules. The sugar is believed to act as a replacement for water or to keep the protein vitrified. Although usually only one of the mechanisms is considered, in this study both were found to play a role. The importance of either mechanism depends on the storage temperature and ambient humidity, which should therefore be taken into account when developing dry stabilized protein formulations.
Furthermore, the drying technique should also be considered during the development. For example, because spray drying can be stressful to the protein, the process conditions can largely affect the quality of the product. Therefore, also the drying process should be tailored to the specific protein to be formulated. Therefore, a mathematical model was developed to predict optimal process conditions.
It is believed that more detailed models can further help with the formulation and process development by understanding better what happens at a more microscopic level. For protein formulations, predicting the behavior of drying droplets showed and quantified the separation of the stabilizing sugar and the protein on a molecular level inside the droplet. With this knowledge a better approach can be chosen to obtain optimal protein stability.