Anakinra Formulation Without Sodium Citrate for Stability
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Solution Overview
Problem
Current pharmaceutical compositions containing anakinra for treating IL-1 mediated disorders often cause injection site reactions due to the use of sodium citrate, which can lead to aggregation and stability issues, necessitating the development of formulations without sodium citrate.
Innovation Solution
Anakinra is formulated in an aqueous solution with appropriate tonicity agents and stabilizers, such as EDTA and polysorbate 80, without sodium citrate, allowing the protein to inherently control solution pH and maintain stability, thereby avoiding aggregation and injection site reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If sodium citrate is used as a buffering agent in anakinra formulations, then pH stability is improved, but injection site reactions and local intolerance increase
Solution Approach 1:
The patent removes sodium citrate from the formulation entirely, extracting the problematic buffering agent that causes injection site reactions. The formulation achieves pH stability without citrate by relying on the inherent buffering capacity of the protein drug anakinra itself and using alternative tonicity agents, thus eliminating the harmful effect while maintaining pH control.
Solution Approach 2:
The patent enables anakinra to serve its own buffering function. The protein drug inherently controls solution pH through its amino acid composition and ionization properties, eliminating the need for external buffering agents like sodium citrate. This self-service approach maintains pH stability while avoiding injection site reactions caused by exogenous buffers.
2Stability of the object's composition
If sodium citrate is used to maintain pH stability, then formulation stability is improved, but protein aggregation increases
Solution Approach 1:
The patent extracts sodium citrate from the formulation to prevent citrate-induced protein aggregation. By removing this specific buffering agent, the formulation avoids triggering aggregation pathways associated with citrate while maintaining pH stability through alternative means, thus improving overall formulation stability without aggregation.
Solution Approach 2:
The formulation uses anakinra's inherent properties to maintain stability without external buffering agents that could induce aggregation. The protein's own ionization characteristics provide sufficient pH control to prevent aggregation, eliminating the need for citrate-based buffering that would otherwise trigger aggregation events.
3Stability of the object's composition
If buffer concentration is increased to improve pH control, then pH stability is improved, but local tolerance at injection site worsens
Solution Approach 1:
The patent eliminates the need for high buffer concentrations by enabling anakinra to self-regulate pH. The protein's inherent buffering capacity provides sufficient pH control at physiological buffer levels, maintaining both pH stability and local tolerance without requiring excessive buffer concentrations that would cause injection site reactions.
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 achieves stability and reduced injection site reactions, maintaining therapeutic efficacy while minimizing aggregation and pH instability, comparable to formulations with sodium citrate, and effectively treats IL-1 mediated disorders.
Implementation Method 1
EDTA and polysorbate 80 are used as stabilizers
Implementation Method 2
EDTA and polysorbate 80 are used as stabilizers
Data Source
AI summary
The present invention relates to pharmaceutical compositions comprising anakinra as an active compound in the absence of sodium citrate. The said pharmaceutical compositions are useful for the treatment of IL-1 mediated disorders and for decreasing nociceptive pain during such treatment.