The Impact of the Water Evaporation Rate and Saccharide Excipients on the Oxidative Degradation of Polysorbates During Oven Drying and Spray Drying.

In recent years, many fast drying techniques such as spray-drying are being explored as alternatives to biopharmaceutical freeze-drying. Thus, it is essential to understand how the processability of commonly used excipients will be affected when these new techniques are employed. This study reports a series of observations outlining how the thermally-induced oxidative degradation of polysorbates (PS) evolves in liquid to solid transitions, such as those expected in spray-drying. Firstly, the impact of different evaporation rates on the oxidative degradation of aqueous solutions of two different PS types namely, PS20 and PS80, were screened via evaporative solvent casting. The latter revealed that the evaporation rate could critically impact the rate-limiting steps of PS thermal oxidation. In addition, the potential of saccharides as excipients to mitigate the thermal oxidation of PS80 under slow and fast evaporation conditions was investigated. Five different saccharide excipients were screened, i.e., trehalose dihydrate, maltodextrin, hydroxypropyl-β-cyclodextrin, and Dextran 40. Under slow evaporation conditions, only trehalose dihydrate seemed to be beneficial in avoiding the thermal oxidation of PS80. For fast evaporation conditions, hydroxypropyl-β-cyclodextrin prevented the oxidative degradation of PS80. This implies that distinct strategies to mitigate PS oxidative degradation might be necessary depending on the drying process and rates.