Effects of Excipients on the Chemical and Physical Stability of Glucagon during Freeze-Drying and Storage in Dried Formulations

To evaluate the effects of several buffers and excipients on the stability of glucagon during freeze-drying and storage as dried powder formulations. The chemical and physical stability of glucagon in freeze-dried solid formulations was evaluated by a variety of techniques including mass spectrometry (MS), reversed phase HPLC (RP-HPLC), size exclusion HPLC (SE-HPLC), infrared (IR) spectroscopy, differential scanning calorimetry (DSC) and turbidity. Similar to protein drugs, maintaining the solid amorphous phase by incorporating carbohydrates as well as addition of surfactant protected lyophilized glucagon from degradation during long-term storage. However, different from proteins, maintaining/stabilizing the secondary structure of glucagon was not a prerequisite for its stability. The formulation lessons learned from studies of freeze-dried formulations of proteins can be applied successfully to development of stable formulations of glucagon. However, peptides may behave differently than proteins due to their small molecule size and less ordered structure.