Development of a highly stable, nonaqueous glucagon formulation for delivery via infusion pump systems

Background: Despite a vigorous research effort, to date, the development of systems that achieve glucagon stability in aqueous formulations (without reconstitution) has failed to produce any clinical candidates. We have developed a novel, nonaqueous glucagon formulation based on a biocompatible pharmaceutical solvent, dimethyl sulfoxide, which demonstrates excellent physical and chemical stability at relatively high concentrations and at high temperatures. Methods: This article reports the development of a novel, biocompatible, nonaqueous native human glucagon formulation for potential use in subcutaneous infusion pump systems. Results: Data are presented that demonstrate physical and chemical stability under presumed storage conditions (2 years at room temperature) as well as "in use" stability and compatibility in an Insulet's OmniPod infusion pump. Also presented are results of a skin irritation study in a rabbit model and pharmacokinetics/pharmacodynamics data following pump administration of glucagon in a diabetic swine model. Conclusions: This nonaqueous glucagon formulation is suitable for further clinical development in pump systems.