Barry Derham1, Joona Sundqvist1, Faheem Ahmed Bhatti1, Sami Ikävalko1, Juho Kukkonen1, Juha Kontturi1, Josetta Silfvast1, Maria Lume1 & Gunilla Petersson2
1Nanoform Finland Oyj, Viikinkaari 4, 00790 Helsinki, Finland
2Inhaled Delivery Consulting AB, Lovartsgatan 13, SE-211 74 Malmoe, Sweden
Summary
Semaglutide (SMG) is a glucagon-like peptide-1 (GLP-1) receptor agonist that was modified to increase the half-life from two minutes to approximately one week. It has shown significant results in the treatment of type 2 diabetes and obesity. The opportunity to shift from subcutaneous injection to an inhaled product of SMG for systemic effect would enhance patient adherence and convenience. Nanoform’s proprietary Bio platform technology (Bioline) can manufacture formulated biological drug particles of tuneable size and morphology, while retaining biological activity. The technology can be applied across various delivery routes. For inhalation, suitable particle sizes can be easily produced. Formulation development and manufacturing were focused on the production of a physicochemical stable formulation, with improved aerodynamic particle size distribution. No chemical degradation or physical change was observed during the formulation manufacturing process. The powder aerosol showed a low MMAD and high fine particle fraction. A down-selected formulation showed stability at 25°C/60% RH for 3 months. Dissolution testing of the SMG formulation at three dose levels was conducted. The dose was captured on a membrane filter using a modified Andersen Cascade Impactor (mACI) and a pre-separator with a 5 µm cut off. The dissolution testing was performed with USP paddle over disk at pH, 6.0 and 7.5. Dissolution was rapid, 80% is dissolved after 2 minutes and complete dissolution after 30 minutes at both pH’s. A stable formulation of semaglutide suitable for inhalation delivery for a systemic effect has been developed and is ready for further preclinical in vivo testing.