GLP-1/GLP-2 Dual Agonist Formulation Preservative Stability
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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 degradation and reduced efficacy, making it unpredictable to maintain stability and effectiveness.
Innovation Solution
The development of pharmaceutical compositions comprising a GLP-1/GLP-2 dual agonist peptide with specific preservatives like benzoate, benzalkonium chloride, and benzyl alcohol in a phosphate buffer system, which maintains chemical and physical stability without detrimental effects on the peptide, allowing for multi-dose administration without significant oligomerization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If preservatives are added to prevent microbial growth, then safety and shelf-life are improved, but chemical stability and physical stability of the peptide deteriorate
Solution Approach 1:
The patent applies parameter changes by carefully controlling the concentration of preservatives (e.g., phenol at 0.5-2.0%, cresol at 0.5-2.0%) and adjusting pH levels (6.5-7.5) to optimize the balance between microbial protection and peptide stability. This quantitative adjustment resolves the contradiction by finding optimal parameter values that satisfy both safety and stability requirements.
Solution Approach 2:
The patent uses composite formulations combining multiple excipients including preservatives (phenol, cresol), buffers (phosphate, citrate), tonicity agents (mannitol, NaCl), and antioxidants (ascorbic acid, EDTA). This composite approach allows the preservative system to work synergistically with other components, maintaining peptide stability while providing effective microbial protection.
2Duration of action of stationary object
If preservatives are added to enable multi-dose storage, then duration of action is improved, but peptide degradation increases
Solution Approach 1:
The patent applies preliminary action by incorporating preservatives and stabilizing excipients into the formulation before storage. This pre-established protective system prevents peptide degradation during extended multi-dose storage, allowing the composition to maintain stability throughout its shelf-life without significant peptide loss.
Solution Approach 2:
The patent uses intermediary substances such as buffers (phosphate, citrate) and antioxidants (ascorbic acid, EDTA) that mediate between the preservative system and the peptide. These intermediaries protect the peptide from preservative-induced degradation while allowing the preservatives to effectively prevent microbial growth during multi-dose storage.
3Ease of operation
If excipients are added to enhance solubility and stability, then ease of operation is improved, but negative interactions such as aggregation and fibrillation increase
Solution Approach 1:
The patent applies parameter changes by optimizing concentrations of solubilizing excipients (mannitol at 10-500 mM, NaCl at 10-200 mM) and adjusting pH (6.5-7.5) to maximize solubility while minimizing aggregation. This quantitative optimization resolves the contradiction by finding the optimal parameter range where solubility is enhanced without inducing harmful aggregation.
Solution Approach 2:
The patent uses intermediary substances such as hydrophilic polymers (polyethylene glycol, hydroxypropyl cellulose) and surfactants (polysorbate 20, polysorbate 80) that mediate between the peptide and the formulation environment. These intermediaries enhance solubility and prevent aggregation by providing steric stabilization and reducing inter-peptide interactions that lead to fibrillation.
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 compositions effectively prevent microbial growth while maintaining the stability and potency of the GLP-1/GLP-2 dual agonist, enabling prolonged use without significant degradation or oligomerization, thus ensuring the composition's effectiveness and safety over extended periods.
Implementation Method 1
The greatest control over hydrolytic reactions, including deamidation, is exerted by stable and reliable pH and buffer systems
Implementation Method 2
Preservatives may be added to pharmaceutical compositions to kill microorganism contaminants
Data Source
AI summary
The present invention relates to pharmaceutical compositions comprising particular preservatives.