title: Development of stable liquid glucagon formulations for use in artificial pancreas.
abstract: A promising approach to treat diabetes is the development of fully automated artificial/bionic pancreas systems that use both insulin and glucagon to maintain euglycemia. A physically and chemically stable liquid formulation of glucagon does not currently exist. Our goal is to develop a glucagon formulation that is stable as a clear and gel-free solution, free of fibrils and that has the requisite long-term shelf life for storage in the supply chain, short-term stability for at least 7 days at 37°C, and pump compatibility for use in a bihormonal pump. We report the development of two distinct families of stable liquid glucagon formulations which utilize surfactant or surfactant-like excipients (LMPC and DDM) to "immobilize" the glucagon in solution potentially through the formation of micelles and prevention of interaction between glucagon molecules. Data are presented that demonstrate long-term physical and chemical stability (~2 years) at 5°C, short-term stability (up to 1 month) under accelerated 37°C testing conditions, pump compatibility for up to 9 days, and adequate glucose responses in dogs and diabetic swine. These stable glucagon formulations show utility and promise for further development in artificial pancreas systems.
authors.affiliation: Biodel Inc, Danbury CT, USA rpohl@biodel.com.
authors.forename: Roderike
authors.initials: R
authors.lastname: Pohl
authors.affiliation: Biodel Inc, Danbury CT, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Biodel Inc, Danbury CT, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Krasner
authors.affiliation: Biodel Inc, Danbury CT, USA.
authors.forename: Errol
authors.initials: E
authors.lastname: De Souza
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000473:pathology; D004285:Dogs; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008297:Male; D019397:Pancreas, Artificial; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry; D013552:Swine
chemical_list: D019999:Pharmaceutical Solutions; D005934:Glucagon
keywords: artificial pancreas; bihormonal pump; liquid glucagon; stabilized glucagon