Anakinra Formulation Stability via HEPES Buffering
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Solution Overview
Problem
Existing protein drug formulations, particularly those for ophthalmic use, face challenges with the poor stability of active proteins, which affects their efficacy and longevity during storage and administration, especially under elevated temperatures and mechanical stress.
Innovation Solution
The development of novel anakinra compositions using HEPES buffer, optionally combined with sodium citrate, and osmolytes like taurine or hydroxyproline, which stabilize the protein at concentrations from 0.01 mg/mL to 30 mg/mL, maintaining pH stability and osmolality, thereby enhancing storage and handling stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If sodium citrate is used as buffer component to stabilize anakinra, then protein stability is improved, but local irritation at injection site increases
Solution Approach 1:
The patent changes the buffer component from sodium citrate to HEPES, altering the chemical parameters of the formulation. This substitution maintains anakinra stability while eliminating the local irritation issue associated with citrate, as HEPES does not cause the same degree of tissue irritation.
Solution Approach 2:
The patent employs sodium citrate at minimized concentrations or in combination with HEPES, using it temporarily during specific formulation stages or in formulations where its stabilizing effect is most needed, while relying primarily on HEPES for long-term stability and tolerance.
2Reliability
If protein concentration is increased to improve therapeutic efficacy, then treatment effectiveness is improved, but protein aggregation increases
Solution Approach 1:
The patent optimizes the concentration parameters of anakinra within the range of 0.01 mg/mL to 30 mg/mL, finding the optimal balance point where therapeutic efficacy is achieved without excessive aggregation. The buffer system (HEPES/sodium citrate) is adjusted concurrently to maintain stability at these concentrations.
Solution Approach 2:
The HEPES buffer acts as an intermediary substance that mediates between the anakinra protein molecules, preventing direct protein-protein aggregation while maintaining sufficient protein concentration for therapeutic effect. The buffer system provides a protective ionic environment that stabilizes the protein structure.
3Ease of operation
If storage temperature is elevated to improve handling, then ease of administration is improved, but protein degradation increases
Solution Approach 1:
The patent modifies the formulation parameters by incorporating HEPES buffer and osmolytes, which change the thermal stability characteristics of the anakinra solution. This allows the protein to withstand elevated temperatures during handling and administration without significant degradation, expanding the acceptable temperature range.
Solution Approach 2:
The buffer system and osmolytes are incorporated in advance to provide protective effects against thermal stress before it occurs. The formulation is pre-designed to cushion against protein degradation that would otherwise occur during temperature fluctuations during handling and administration.
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 exhibit improved stability under various conditions, including long-term refrigeration and short-term ambient storage, reducing protein degradation and maintaining therapeutic effectiveness, making them suitable for topical ophthalmic administration.
Implementation Method 1
buffer, selected from HEPES and a mixture of HEPES and sodium citrate, wherein said buffer stabilizes the pH of the composition at a pH of from 6 to 7
Implementation Method 2
optionally at least one osmolyte
Data Source
AI summary
The present invention relates to compositions comprising anakinra, buffer, and optionally at least one osmolyte and optionally further excipients. Further, the present invention relates to use of said compositions for treatment of for example ophthalmic disorders.