Abstract:
PURPOSE:To evaluate the effects of several buffers and excipients on the stability of glucagon during freeze-drying and storage as dried powder formulations. METHODS: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. RESULTS: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. CONCLUSIONS: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.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Fang WJ,Qi W,Kinzell J,Prestrelski S,Carpenter JFdoi
10.1007/s11095-012-0820-7subject
Has Abstractpub_date
2012-12-01 00:00:00pages
3278-91issue
12eissn
0724-8741issn
1573-904Xjournal_volume
29pub_type
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