Characterising Protein DPI Formulations: How and why does the dissolution behaviour change?

Friederike Roth, Regina Scherließ

Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, Kiel, 24118, Germany

Summary

Treating lung diseases with high molecular protein drugs is still limited by their inability to penetrate well through the pulmonary tissue. Local pulmonary application facilitates treatment with these protein drugs. Furthermore, it would broaden the application possibilities of smaller proteins and peptides that are able to penetrate through the epithelium. The application via the lung is a suitable alternative to the commonly used parental application. To ensure the stability of the sensitive protein drugs during storage an inhalable dry powder formulation is a good option. The most suitable production method for protein DPI formulations is spray drying. This, however, comes with various stress factors for the protein and can thereby change the properties of the protein. This study focuses on observed changes in the dissolution behaviour. It aims to characterise these changes and to find a structural explanation. We used ovalbumin as a model protein and compared the commercial lyophilisate with ovalbumin spray-dried with two different spray-drying nozzles: the two-fluid nozzle and the ultrasonic nozzle. As a characterising method, we choose the Franz cell dissolution measurements. The obtained dissolution profiles show differences in dissolution velocity. Although a morphological explanation seems obvious, experimental observations indicate further changes. Further experiments to characterise these changes are ongoing It was not possible to find a structural explanation for these dissolution changes with the used methods. Neither XRPD measurements nor fluorescence emission spectra assay showed structural changes after spray drying. The search for a method to identify the structural explanation for the observed changes continues.

Key Message

Dry powder formulations for inhalation seem to be promising for protein drugs. Nevertheless, the production method can influence proteins not only in their biological effect, but also in physical characteristics such as dissolution profile. Our research aims to investigate the resulting structural changes. We were able to characterise the dissolution behaviour changes after spray drying; the search for a structural explanation, however, continues.