Stabilized Glucagon Formulation for Bihormonal Pump Use

Abstract

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.