Spray drying of protein precipitates and evaluation of the nano spray dryer B-90

The objective of the present thesis was to tread new paths in pharmaceutical spray drying. Compared to other drying techniques in formulation development, spray drying offers the advantage of a comprehensive particle design depending on the intended application of the powder. Moreover, spray drying is characterized by short process times and moderate acquisition costs for lab scale equipment. The application of spray drying for the production of stable protein powders was evaluated. As a matter of principle, spray drying challenges protein stability. The atomization of the spray solution leads to a tremendous increase of the air-–liquid interface, at which proteins with inherent surface affinity tend to adsorb. Adsorption is often followed by protein unfolding and subsequently aggregation, which are seen as critical with respect to safety and efficacy. The default measure to prevent protein adsorption in the first place constitutes the addition of a surfactant to the spray solution. Surfactant molecules are known to compete with protein molecules for the interfacial space. However, the use of surfactants, especially polysorbates, may be associated with a reduced long-term protein stability due to enhanced protein oxidation by residual peroxides. Instead of adding surfactant to the spray solution, the concept of protein precipitation before spray drying was investigated as alternative approach to stabilize proteins against interface related stress. Protein precipitation by ‘salting-out’ was conducted for a monoclonal IgG1 antibody and recombinant human interleukin-11 (rhIL-11) using volatile ammonium salts. The volatility of the precipitating salts was considered to be of high importance, as their elimination from the final protein formulation was to be accomplished at the increased temperature during spray drying. Specifically, ammonium carbamate showed appropriate qualities as precipitating agent.