Spray drying for protein stabilization

During formulation development, stabilizing buffers and excipients are added to therapeutic proteins to overcome their intrinsic instability. Another approach is their solidification using techniques like freeze drying or spray drying (SD). In this work, to enhance the stability of three proteins (α-chymotrypsin, catalase and Horseradish Peroxidase (HRP)), suitable buffers and excipients were selected in solution state for three formulations (referred to as concepts) for each protein using Differential Scanning Fluorimetry (DSF) combined with Static Light Scattering (SLS). Two of these concepts were supposed to stabilize the protein and one was less stabilizing. Then, SD was performed, and the protein stability was compared to that prior SD using dynamic light scattering, UV-VIS spectroscopy, far-UV circular dichroism, size-exclusion and reversed-phase chromatography. While the selected excipients did not differ much from the ones used during a previous study on Bovine Serum Albumin (BSA), Immunoglobulin G (IgG) and lysozyme, clear stability differences during solidification were observed. The measured recovery was partly 40 % lower than prior to SD and only one catalase concept was able to maintain its original concentration. While the stability of two catalase concepts was correctly predicted by DSF/SLS, it was not the case for the other proteins. This outcome led to the question whether it is sufficient to determine protein stability during solidification using DSF/SLS or if a more holistic approach is necessary.