Effects of excipients on the chemical and physical stability of glucagon during freeze-drying and storage in dried formulations.

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 Res

journal_title

Pharmaceutical research

authors

Fang WJ,Qi W,Kinzell J,Prestrelski S,Carpenter JF

doi

10.1007/s11095-012-0820-7

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

3278-91

issue

12

eissn

0724-8741

issn

1573-904X

journal_volume

29

pub_type

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