Summary
Semaglutide (SMG) is a Glucagon-like peptide 1 derivative modified to prolong its bioavailability. It is weekly administered subcutaneously using autoinjectors stored under refrigerated conditions. For these reasons a more patient-friendly route, like inhalation, which does not require cold chain can be advantageous. The aim of this project was to formulate SMG as a spray-dried powder for inhalation maintaining the peptide stable and reaching satisfactory respirability. A pre-formulative study, at 40°C for up to 6h, was conducted on eight solutions which differed in buffer type (Tris and Phosphate) and concentrations (5-10 mM) and in the concentration of SMG, L-leucine and trehalose (0.5 or 0.8% w/w). No effect on the concentration of the peptide was observed by Reverse Phase High Pressure Liquid Chromatography, no aggregates were identified by Size Exclusion Chromatography and mass spectrometry did not show any evidence of chemical degradation. Two solution compositions were then chosen and spray-dried at fixed process parameters. Although different buffers were used, the powders obtained did not present any degradation of the peptide and had a similar water content (<4% w/w). However, the powder obtained from the Phosphate buffer showed a higher Fine Particle Fraction (59.8%) and higher Extra Fine Particle Fraction (21.6%), indicating a potential higher alveolar deposition, and, therefore, systemic absorption. Employing pre-formulative studies it was possible to readily obtain a dry powder which preserved the peptide and was respirable. Optimization of powder composition and spray drying process parameters as well as feasibility study focused on industrialising the DPI SMG product will be carried out.