Glucagon Peptide Formulation Using pH Memory and Aprotic Solvent
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Solution Overview
Problem
Current glucagon rescue medications for severe hypoglycemia are difficult to use in emergency situations due to complex reconstitution procedures and poor stability at nonrefrigerated temperatures, requiring refrigeration and having limited solubility in water, which complicates their administration and storage.
Innovation Solution
A stable glucagon formulation is developed using a peptide dried in a non-volatile buffer with a pH memory, reconstituted in an aprotic polar solvent like DMSO, maintaining low moisture content and stability over a range of temperatures, allowing for simple and effective administration without reconstitution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If glucagon is formulated as a freeze-dried powder requiring reconstitution, then storage stability at nonrefrigerated temperatures is improved, but ease of operation deteriorates due to complex reconstitution procedures
Solution Approach 1:
The patent changes the physical state parameter of glucagon from freeze-dried powder to a stable concentrated solution formulation. This allows the medication to maintain stability at nonrefrigerated temperatures while eliminating the need for reconstitution, directly resolving the contradiction between storage stability and ease of administration
Solution Approach 2:
The patent uses a composite formulation system combining glucagon with specific excipients and stabilizing agents in a concentrated solution. This composite material approach enables the solution to remain stable without refrigeration while being ready for immediate injection, simultaneously achieving both storage stability and operational simplicity
2Ease of operation
If glucagon is formulated as a concentrated solution, then ease of operation is improved by eliminating reconstitution steps, but storage stability deteriorates at nonrefrigerated temperatures
Solution Approach 1:
The patent optimizes the concentration parameter and pH parameter of the glucagon solution, along with incorporating stabilizing excipients. These parameter changes enable the concentrated solution to maintain stability at nonrefrigerated temperatures while remaining ready for immediate use, resolving the contradiction between ease of operation and storage stability
3Ease of operation
If glucagon is formulated with high moisture content, then solubility and ease of administration are improved, but stability deteriorates over extended storage periods
Solution Approach 1:
The patent carefully controls the moisture content parameter and optimizes the solvent composition parameter. By using a non-aqueous or low-aqueous solvent system with appropriate stabilizers, the formulation achieves sufficient solubility for ease of administration while maintaining stability over extended storage periods at nonrefrigerated temperatures
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation provides a stable and user-friendly glucagon rescue medication that can be stored at nonrefrigerated temperatures for extended periods, ensuring effective treatment of severe hypoglycemia with improved solubility and stability, applicable for various peptides with poor aqueous stability.
Implementation Method 1
the peptide has been dried in a non-volatile buffer, and wherein the dried peptide has a pH memory that is about equal to the pH of the peptide in the non-volatile buffer
Implementation Method 2
wherein the moisture content of the formulation is less than 5%
Data Source
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AI summary
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.