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

J Diabetes Sci Technol. 2015 Jan;9(1):24-33. doi: 10.1177/1932296814565131.

Abstract

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. This article reports the development of a novel, biocompatible, nonaqueous native human glucagon formulation for potential use in subcutaneous infusion pump systems. 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. This nonaqueous glucagon formulation is suitable for further clinical development in pump systems.

Keywords: glucagon; hypoglycemia; infusion; nonaqueous.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Delivery Systems
  • Drug Stability
  • Glucagon / administration & dosage*
  • Glucagon / chemical synthesis*
  • Glucagon / chemistry
  • Infusion Pumps*
  • Male
  • Rabbits
  • Swine

Substances

  • Glucagon