Stability and stabilization of insulinotropin in a dextran formulation.
The stability of insulinotropin in a formulation containing 23% dextran-75 is studied. The effects of temperature, excipients, dextran concentration, and drug concentration on the stability of insulinotropin are examined. The tryptophan residue is identified as the primary degradation site in the insulinotropin molecule by LC-MS. Different antioxidants are used to stabilize the peptide. The combination of cysteine and EDTA is found to be most effective in stabilizing insulinotropin in the dextran formulation.
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Pharmaceutical Research and Development, Pfizer Central Research, Groton, Connecticut, USA.
Heller
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D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D004355:Drug Stability; D004492:Edetic Acid / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010446:Peptide Fragments; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D013696:Temperature
D002021:Buffers; D003911:Dextrans; D005079:Excipients; D010446:Peptide Fragments; D010455:Peptides; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D004492:Edetic Acid; D003545:Cysteine; C051322:glucagon-like peptide 1 (7-37)