Aqueous Peptide Formulations with Minimal Buffer for Stability
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Solution Overview
Problem
Peptide therapeutic agents in aqueous solutions are unstable due to structural degradation, which is exacerbated by the presence of buffers, and maintaining stability at elevated temperatures is challenging, especially in the pH range of 4.0-7.5 where many peptides do not provide sufficient buffering capacity.
Innovation Solution
Formulating peptide therapeutic agents with minimal buffer concentration (0-5 mM) and optionally adding a stabilizer such as an amino acid or polyol, while ensuring the pH is maintained between 4.0 and 7.5, thereby minimizing buffer impact and enhancing stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If buffer concentration is increased to maintain pH stability, then pH control is improved, but peptide stability deteriorates due to buffer-induced degradation
Solution Approach 1:
The invention extracts and removes the harmful buffer component from the formulation while retaining pH control through alternative means (peptide self-buffering or minimal buffer at 0-5 mM), thereby eliminating buffer-induced degradation while maintaining pH stability
Solution Approach 2:
The invention enables the peptide to serve its own buffering needs through self-buffering capability, where the peptide's ionizable groups provide pH stability without requiring external buffer additives, thus improving stability while maintaining pH control
2Ease of operation
If storage temperature is increased to 25°C or 30°C for patient convenience, then ease of operation is improved, but peptide stability deteriorates due to accelerated degradation
Solution Approach 1:
The invention changes the formulation parameters (buffer concentration to 0-5 mM, addition of stabilizers, pH optimization) to enable the peptide to remain stable at elevated temperatures (25-30°C), thus improving storage convenience without sacrificing stability
3Reliability
If peptide concentration is maintained in aqueous solution for therapeutic efficacy, then effectiveness is improved, but stability deteriorates due to susceptibility to degradation
Solution Approach 1:
The invention extracts the harmful aqueous environment's degradation-promoting aspects while retaining the beneficial aqueous solubility, by removing buffers and adding stabilizers to create a modified aqueous environment that supports both solubility and stability
Solution Approach 2:
The invention introduces stabilizer molecules as intermediaries that mediate between the peptide and the aqueous environment, protecting the peptide from degradation while allowing it to remain dissolved and therapeutically effective
Data Source
AI summary
There is provided, inter alia, an aqueous solution composition of pH in the range 4.0-7.5 comprising: a peptide therapeutic agent; optionally one or more buffers being substances having at least one ionisable group with a pK a in the range 3.0 to 8.5 and which pk a is within 2 pH units of the pH of the composition; and a stabilizer; wherein the peptide therapeutic agent does not contain ionisable groups with pk a in the range 3.0 to 8.5, and wherein the buffers are present in the composition at a total concentration of 0-5 mM.