Protein Drugs for Inhalation: Investigating the Stability of Dry Powder Formulations during Production and Application
The pulmonary application of protein drugs broadens the therapeutical option for several severe lung diseases. The formulation as an inhalable dry powder increases the storage stability, is easy to formulate and highly environmentally friendly. For proteins these dry powders are best prepared by spray drying. The spray drying process, however, exposes the protein to various stress factors during the different phases of the process. This thesis, therefore, aimed to identify and characterise destabilising factors that occur during the production and application of inhalable protein drugs. Spray dryers using different techniques and atomisation nozzles were compared. Each exposed the protein to varying levels and types of stress factors and ultimately affected the structure of the protein in different ways. The degradation was also depending on the stage of spray drying and the spray drying temperature. As stabilising excipients glycine and mannitol were able to protect the structure of the model protein chymotrypsin during the spray drying process to a high extent. Small structural changes, however, still occurred. Furthermore, spray drying changed the dissolution behaviour of the model protein ovalbumin in terms of dissolution velocity, solubility and wettability. Dissolution behaviour analysis was found as a fast, easy to perform and sensitive method to detect changes in dry powder protein formulation. Last, the investigation of application opportunities revealed two possibilities. First, the inhalable dry powder (DPI) formulation exhibited an aerodynamic performance suitable for dry powder inhalation. Second, this work found that the formulation could be redispersed and applied using a nebuliser. This would be an option to deliver the protein drug to the lung of patients that are not able to use a DPI device, due to e. g. poor lung function.
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