title: Development of a highly stable, nonaqueous glucagon formulation for delivery via infusion pump systems.
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.
authors.affiliation: Xeris Pharmaceuticals, Inc, Austin, TX, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Newswanger
authors.affiliation: Xeris Pharmaceuticals, Inc, Austin, TX, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Ammons
authors.affiliation: Xeris Pharmaceuticals, Inc, Austin, TX, USA.
authors.forename: Neelima
authors.initials: N
authors.lastname: Phadnis
authors.affiliation: Legacy Health and Legacy Research Institute, Portland, OR, USA Pacific Diabetes Technologies, Portland, OR, USA.
authors.forename: W Kenneth
authors.initials: WK
authors.lastname: Ward
authors.affiliation: Oregon Health & Science University, Portland, OR, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Castle
authors.affiliation: Insulet Corporation, Billerica, MA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Campbell
authors.affiliation: Xeris Pharmaceuticals, Inc, Austin, TX, USA stevep@xerispharma.com.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Prestrelski
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D004355:Drug Stability; D005934:Glucagon / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry; D007260:Infusion Pumps; D008297:Male; D011817:Rabbits; D013552:Swine
chemical_list: D005934:Glucagon
keywords: glucagon; hypoglycemia; infusion; nonaqueous