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

Brett Newswanger, Steve Ammons, Neelima Phadnis, W. Kenneth Ward, Jessica Castle, Robert W. Campbell, Steven J. Prestrelski

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalJournal of diabetes science and technology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Infusion Pumps
Glucagon
Pumps
Chemical stability
Pharmacodynamics
Pharmacokinetics
Dimethyl sulfoxide
Subcutaneous Infusions
Temperature
Drug products
Skin
Dimethyl Sulfoxide
Population Groups
Swine
Rabbits
Research
Pharmaceutical Preparations

Keywords

  • glucagon
  • hypoglycemia
  • infusion
  • nonaqueous

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Bioengineering
  • Biomedical Engineering

Cite this

Development of a highly stable, nonaqueous glucagon formulation for delivery via infusion pump systems. / Newswanger, Brett; Ammons, Steve; Phadnis, Neelima; Kenneth Ward, W.; Castle, Jessica; Campbell, Robert W.; Prestrelski, Steven J.

In: Journal of diabetes science and technology, Vol. 9, No. 1, 01.01.2015, p. 24-33.

Research output: Contribution to journalArticle

Newswanger, Brett ; Ammons, Steve ; Phadnis, Neelima ; Kenneth Ward, W. ; Castle, Jessica ; Campbell, Robert W. ; Prestrelski, Steven J. / Development of a highly stable, nonaqueous glucagon formulation for delivery via infusion pump systems. In: Journal of diabetes science and technology. 2015 ; Vol. 9, No. 1. pp. 24-33.
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AU - Campbell, Robert W.

AU - Prestrelski, Steven J.

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