Stable glucagon formulations for the treatment of hypoglycemia

Inactive Publication Date: 2012-02-23
XERIS PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009]The present invention overcome the problems outlined above and advances the art by providing stable glucagon formulations for parenteral injection that can be formulated as solutions, suspensions or pastes. Importantly, the injectable formulations of the present invention advantageously promote uniform delivery of glucagon and provide additional shelf stability against aggregation, oxidation and hydro

Problems solved by technology

However, the desired route of administration places constraints on the therapeutic formulation itself.
However, one of the disadvantages of injectables is the pain and discomfort present at the site of administration associated with certain pharmaceutically active agents, as well as the trauma of having a needle inserted under the skin or into a vein.
Clearly, there can be some degree of discomfort for

Method used

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  • Stable glucagon formulations for the treatment of hypoglycemia
  • Stable glucagon formulations for the treatment of hypoglycemia
  • Stable glucagon formulations for the treatment of hypoglycemia

Examples

Experimental program
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formulation examples

III. Formulation Examples

[0079]The present invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of noncritical parameters which can be changed or modified to yield essentially the same results.

example 1

Preparation of Glucagon Solutions for Use in Freeze-Drying

[0080]Various solutions were prepared to contain glucagon at a concentration of 10 mg / mL. The solutions contained, alternatively, glycine, citrate or phosphate at 5 mM, generally providing a buffer establishing pH of 3. The solution also contained a sugars, alone or in combination, in amounts equal to the w / v amount of glucagon (1:1) or at 200% (2:1) of the amount of glucagon. The sugars were trehalose, HES, and β-cyclodextrin β-CD. Some solutions also contained Tween 20 at 0.10% w / v as a surfactant. The various formulations mixed to substantial homogeneity in amounts as described in Table 1 below:

TABLE 1Glucagon mixtures for subsequent lyophilization.GycineCitratePhosphateTween-GlucagonBufferBufferBufferTrehaloseHESβ-CD20Formulation(mg / ml)(mM)(mM)(mM)(mg / ml)(mg / ml)(mg / ml)(mg / ml)155000000255000000.01355001000045500010005550055006550000100750500000850500000.0195050100001050500100011505055001250500010013500500001450050000.01155...

example 2

Preparation of Dry Glucagon Powder by Freeze-Drying

[0082]The above formulations of Table 1 were pipetted (0.3 mL) into 3-ml lyophilization vials (13-mm ID). The formulations were lyophilized in a FTS Durastop freeze-drier (Stoneridge, N.Y.). Samples were frozen to about −40° C. at a ramp of 2.5° C. / min and maintained for 2 hours (h) to allow sufficient freezing. The sample temperature was then increased to about −5° C. at a ramp of 2° C. / min and held for 2 h as an annealing step. The temperature was then decreased to about −30° C. at a ramp of 1.5° C. / min and the vacuum was turned on at 60 mTorr. The primary drying was set for 24 h. The temperature was gradually increased to about 40° C. at a ramp of 0.5° C. / min and held for additional 10 h. After drying was complete, the vials were capped under vacuum using XX stoppers from the West Pharmaceutical company (product #10123524). None of the formulations showed any evidence of cake collapse following freeze-drying. These formulations w...

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Abstract

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.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims priority to and the benefit of U.S. Provisional Application No. 61 / 365,637, filed Jul. 19, 2010 and entitled “Stable Glucagon Formulations for the Treatment of Hypoglycemia,” the entire disclosure of which is herein incorporated by reference for all purposes.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under grant number DK085809 awarded by The National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Parenteral injection refers to the administration of drugs or vaccines via injection under or through one or more layers of skin or mucus membranes of an animal. Standard injections are given into the subcutaneous or intramuscular region of an animal, e.g., a human patient. These deep locations are targeted because the tissue expands more easily, relative to shal...

Claims

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Application Information

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IPC IPC(8): A61K38/26C07K14/605A61P3/08
CPCA61K9/0019A61K9/19A61K38/26A61K47/02A61K47/40A61K47/183A61K47/26A61K47/36A61K47/12A61P3/08A61P3/10A61P7/12
Inventor PRESTRELSKI, STEVENFANG, WEI-JIECARPENTER, JOHN F.KINZELL, JOHN
Owner XERIS PHARMA
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