Xeris Pharmaceuticals, Inc.

Powderject Research Limited

Other

University of Colorado

Amylin Pharmaceuticals, Inc.

Steven J Prestrelski

John Kinzell

Michael A Sandoval

Martin J Donovan

Kevin J Brodbeck

Nancy Scott

Terry L Burkoth

Yuh-Fun Maa

Brian R Sloat

John Frank Carpenter

Barbara Horsey O'Connor

Manley Huang

Christopher A Rhodes

Gregg Stetsko

Andrew Gordon Muddle

Jessica G Smith

Wei-Jie Fang

Evan Cassavaugh

Roderick Hafner

Victoria Knepp Maskiewicz

John TH Ong

The present invention relates to the use of aprotic polar solvents and an ionization stabilizing agent to prepare storage stable sustained release therapeutic formulations by dissolving a therapeutic agent (active ingredient) in an aprotic polar solvent system that can then be administered to patients suffering from or predisposed to a variety of physical conditions or disorders, notably hypoglycemia. In certain embodiments, the invention is directed to formulations comprising one or more therapeutic agents, as well as methods of making such formulations, comprising at least one therapeutic agent dissolved in an aprotic polar solvent such as DMSO, comprising at least one ionization stabilizing excipient (suitably, a mineral acid) and at least one sustained release modifier (suitably, a divalent cation-donating compound such as a zinc salt and/or a polymer such as a PLGA) in concentrations sufficient to impart physical and chemical stability to the therapeutic agent and to produce a formulation that results in a sustained release of the therapeutic agent into the bloodstream of an animal to which the formulation has been administered. The invention also relates to methods of producing such storage stable sustained release therapeutic formulations and to methods of treating, preventing and diagnosing certain physical conditions and disorders, notably hypoglycemia, by administering such storage stable sustained release therapeutic formulations to a patient.

Stable sustained release therapeutic compositions in aprotic polar solvents and methods of manufacturing the same

Embodiments of the invention are directed to formulations that provide a solution to the problem of small molecule (e.g., diazepam) precipitation at the injection site when administered as a highly-concentrated formulation. In certain aspects the formulations include at least one surfactant in a non-aqueous formulation, which prevents small molecule precipitation and improves the bioavailability of the drug by enhancing absorption into the systemic circulation.

Precipitation resistant small molecule drug formulations

Certain embodiments are directed to a formulation of a therapeutic agent, as well as a method of making such a formulation, comprising at least one therapeutic agent dissolved in an aprotic polar solvent system comprising at least one ionization stabilizing excipient in a concentration sufficient to impart physical and chemical stability to the therapeutic agent.

Methods for producing stable therapeutic glucagon formulations in aprotic polar solvents

Disclosed is a stable liquid formulation for parenteral injection comprising a biocompatible non-aqueous solvent and a small molecule drug, or a salt thereof, solubilized within the non-aqueous solvent, wherein the liquid formulation comprises less than 10% by weight residual water, and wherein the volume of the liquid formulation to be parenterally injected is from 0.1 &#x3bc;l to 3 ml.

Stable formulations for parenteral injection of small molecule drugs

Stable formulations for parenteral injection of peptide drugs and methods of using such stable formulations are provided. In particular, the present invention provides stable formulations for parenteral injection of glucagon and methods of using such glucagon formulations to treat hypoglycemia, especially severe hypoglycemia in emergency situations.

Stable formulations for parenteral injection of peptide drugs

Methods for producing stable therapeutic formulations in aprotic polar solvents

The delivery of biopharmaceutical and other therapeutic agents parenterally to an animal via a minimally invasive, low pain administration is provided. The agents are delivered to the patient via, e.g., the epidermal, dermal, or subcutaneous layer of the skin in a concentrated form of injectable glucagon that is dissolved in a pharmaceutically acceptable carrier.

Stable glucagon formulations for the treatment of hypoglycemia

Disclosed is a composition for parenteral administration comprising a glucagon peptide which has been dried in a non-volatile glycine buffer, and wherein the glucagon peptide has a pH memory that is about equal to the pH of the glucagon peptide in the non-volatile buffer, wherein the pH memory is between 2.5 to 3.5, an aprotic polar solvent, wherein the peptide is solubilized in the aprotic polar solvent, and wherein the aprotic polar solvent is dimethyl sulfoxide (DMSO), trehalose, glycine, and optionally hydrochloric acid, wherein the moisture content of the composition is less than 5 wt. %.

Compositions for rapidly treating severe hypoglycemia

Disclosed is a paste for injection of a therapeutic agent, the paste comprising an amount of powder comprising an effective amount of the therapeutic agent, wherein the powder is homogeneously contained within a pharmaceutically acceptable carrier, and wherein the paste comprises an injection volume of 0.1 to 3000 microliters.

Pastes for injection of a therapeutic agent

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San Diego, CA, United States of America

Steven J Prestrelski