Stabilized glucagon formulation for bihormonal pump use.
BACKGROUND
A promising approach to treat diabetes is the development of an automated bihormonal pump administering glucagon and insulin. A physically and chemically stable glucagon formulation does not currently exist. Our goal is to develop a glucagon formulation that is stable as a clear ungelled solution, free of fibrils at a pH of 7 for at least 7 days at 37 °C.


METHODS
Experimental glucagon formulations were studied for stability at 25 and 37 °C. Chemical degradation was quantified by reverse phase ultra-performance liquid chromatography. Physical changes were studied using light obscuration and visual observations.


RESULTS
Glucagon content of Biodel glucagon and Lilly glucagon at pH 2 and pH 4, as measured by high-performance liquid chromatography at 25 °C, was 100% at 7 days compared to 87% and <7%, respectively. Light obscuration measurements indicated Lilly glucagon at pH 4 formed an opaque gel, while Biodel glucagon formulation remained a clear solution beyond 50 days at 37 °C. Visual observations confirmed these results.


CONCLUSIONS
Biodel glucagon is a stabilized formulation at physiological pH and remains chemically and physically stable beyond 7 days at 37 °C, suggesting its utility for use in a bihormonal pump.
Biodel Inc., Danbury, Connecticut 06810, USA. ssteiner@biodel.com
Solomon S
SS
Steiner
Ming
M
Li
Robert
R
Hauser
Roderike
R
Pohl
D000438:Alcohols / Q000737:chemistry; D002021:Buffers; D002241:Carbohydrates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005934:Glucagon / Q000008:administration & dosage* / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007332:Insulin Infusion Systems; D008244:Lysophosphatidylcholines / Q000737:chemistry; D019999:Pharmaceutical Solutions; D019163:Reducing Agents / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
D000438:Alcohols; D002021:Buffers; D002241:Carbohydrates; D008244:Lysophosphatidylcholines; D019999:Pharmaceutical Solutions; D019163:Reducing Agents; D005934:Glucagon