GLP-1/GLP-2 Peptide Stability with Preservatives
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Solution Overview
Problem
Peptide-based pharmaceutical compositions face challenges such as chemical instability, self-association, and physical instability due to interactions with preservatives, which can lead to reduced efficacy and safety concerns, especially in multi-dose administration settings.
Innovation Solution
The use of specific preservatives like m-cresol and phenol in combination with a GLP-1/GLP-2 dual agonist peptide and phosphate buffer, which maintains chemical and physical stability of the peptide, preventing microbial growth and oligomerization, even at high peptide concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If preservatives are added to pharmaceutical compositions to prevent microbial contamination, then safety is improved, but chemical stability of the peptide deteriorates due to interactions with preservatives
Solution Approach 1:
The patent uses a specific buffer system (phosphate-buffered saline at pH 7.4) as an intermediary substance that mediates between the preservative (m-cresol) and the peptide (GLP-1/GLP-2 dual agonist). The buffer acts as a protective medium that allows the preservative to function while minimizing its direct harmful interactions with the peptide, thereby maintaining chemical stability while ensuring safety through microbial prevention.
2Reliability
If preservatives are used in multi-dose administration settings to prevent microbial growth, then safety is improved, but peptide activity is reduced due to preservative-peptide interactions
Solution Approach 1:
The patent optimizes specific parameters including preservative concentration (0.05-0.5% m-cresol), buffer composition (phosphate-buffered saline), and pH (7.4) to achieve a parameter space where the preservative remains effective against microbes while its negative impact on peptide activity is minimized. This parameter optimization allows multi-dose administration safety without significant loss of peptide therapeutic activity.
3Reliability
If excipients are added to enhance solubility and stability, then positive interactions are achieved, but negative effects occur such as loss of peptide solubility, activity, and chemical/physical stability
Solution Approach 1:
The patent employs a multi-functional excipient system where phosphate-buffered saline serves multiple purposes: maintaining pH stability, providing ionic strength for solubility, and creating a chemical environment that reduces preservative-peptide interactions. This universal buffer system simultaneously addresses solubility, stability, and compatibility with preservatives, avoiding the need for separate excipients that might cause conflicting effects.
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
This approach allows for stable and effective preservation of GLP-1/GLP-2 dual agonist peptides, ensuring prolonged shelf-life and safety in multi-dose administration devices by preventing microbial contamination and maintaining peptide stability, thus enhancing the practicality and safety of peptide-based pharmaceutical compositions.
Implementation Method 1
Pharmaceutical compositions can be sealed and stored in sterile conditions without preservatives being present, but when the container holding the composition is used, any accidental introduction of microorganisms can render the contents unsuitable for further medical use. Therefore, it is important to effectively preserve the pharmaceutical contents
Implementation Method 2
The greatest control over hydrolytic reactions, including deamidation, is exerted by stable and reliable pH and buffer systems
Implementation Method 3
The preservative effect in the composition of the invention allows the composition to be provided in a multi-dose administration setup. The preservative effect prevents growth of microorganisms in the composition over this period, whilst chemical and physical stability of the peptide is maintained
Data Source
AI summary
The present invention relates to pharmaceutical compositions comprising particular preservatives.