Adalimumab Formulation Stability Without Chloride or Amino Acids
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Solution Overview
Problem
High concentration adalimumab compositions tend to aggregate during freeze/thaw and long-term storage, and existing formulations often rely on stabilizers like sodium chloride and amino acids to maintain stability, which is not economically or effectively optimized.
Innovation Solution
Development of a stable aqueous pharmaceutical composition of adalimumab that is free or essentially free of sodium chloride and amino acids, using a buffer system, surfactant, and polyol, with a pH range of 4.5 to 6.5, to maintain long-term stability without these stabilizers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentration compositions of adalimumab are used, then the pharmaceutical composition achieves high drug concentration, but the composition aggregates during freeze/thaw and long term storage
Solution Approach 1:
The patent changes the chemical parameters of the formulation by replacing traditional stabilizers (sodium chloride and amino acids) with a specific combination of buffer system, surfactant, and polyol. This parameter substitution resolves the aggregation issue at high concentrations while maintaining stability during freeze/thaw cycles and long-term storage.
Solution Approach 2:
The patent introduces an intermediary stabilization system consisting of buffer, surfactant, and polyol that mediates between the high concentration adalimumab and the storage conditions. This intermediary system prevents direct interaction between adalimumab molecules that would lead to aggregation, while still allowing high drug concentration to be maintained.
2Stability of the object's composition
If stabilizers such as sodium chloride and amino acids are used, then the stability of adalimumab is maintained, but the formulation becomes less economically optimized
Solution Approach 1:
The patent extracts and removes the traditional stabilizers (sodium chloride and amino acids) from the formulation while replacing them with an alternative stabilization system. This extraction eliminates the need for expensive traditional stabilizers and simplifies the manufacturing process while maintaining adalimumab stability through the buffer-surfactant-polyol combination.
3Stability of the object's composition
If traditional stabilizers are used in the formulation, then adalimumab stability is maintained, but the formulation complexity increases
Solution Approach 1:
The patent merges multiple functions into a unified stabilization system where the buffer, surfactant, and polyol work together as an integrated system. This combination achieves stability maintenance while reducing formulation complexity compared to using multiple separate traditional stabilizers, as the new system is designed to work synergistically as a single formulation package.
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 composition achieves long-term stability for adalimumab, maintaining over 90% activity after six months at various storage conditions, including freeze/thaw cycles, without the need for sodium chloride or amino acids, thus providing a cost-effective and stable formulation for extended storage.
Implementation Method 1
a buffer system, a surfactant and a polyol, wherein the said composition has a pH of about 4.5 to about 6.5
Implementation Method 2
a surfactant selected from group consisting of polysorbate 80, polysorbate 20, polysorbate 40, sodium dodecyl sulfate and poloxamer
Implementation Method 3
a polyol selected from group consisting of mannitol, xylitol, sorbitol, dextran, propylene glycol and polyethylene glycol
Data Source
AI summary
The present relates to stable aqueous pharmaceutical composition of adalimumab comprising (a) buffer system (b) a surfactant and (c) a polyol and the process for the preparation thereof, particularly the suitable aqueous pharmaceutical compositions comprising adalimumab which is free of stabilizers selected from group consisting of sodium chloride and/or amino acids.