Buffer-Free Adalimumab Formulation for High-Concentration Stability
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Solution Overview
Problem
There is a need for additional stable aqueous formulations of high concentration adalimumab, particularly for parenteral administration, that do not rely on traditional buffers to maintain stability and shelf life.
Innovation Solution
A pharmaceutical composition comprising pharmaceutical-grade water with 90 - 110 mg/ml adalimumab, 5 mM to 25 mM salt, 180 mM to 300 mM polyol, and 0.1% polysorbate, without additional buffers, using salts like MgCl2, KCl, NaCl, or CaCl2, and polyols like mannitol or sucrose, to achieve stability for subcutaneous injection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If traditional buffer systems (citrate/phosphate) are used in adalimumab formulations, then pH stability is maintained, but formulation complexity increases and potential stability issues arise
Solution Approach 1:
The patent removes the buffer system from the formulation entirely, extracting the problematic component while maintaining pH stability through alternative means (protein concentration and composition). This resolves the contradiction by eliminating formulation complexity while preserving pH stability.
Solution Approach 2:
The adalimumab protein itself serves as the pH stabilizing agent through its concentration and intrinsic properties, rather than requiring an external buffer system. The formulation uses the active ingredient's own characteristics to maintain stability, reducing overall formulation complexity.
2Stability of the object's composition
If buffer systems are added to maintain pH, then pH control is improved, but the risk of fragmentation and aggregation increases
Solution Approach 1:
By removing the buffer system entirely, the patent eliminates the source of fragmentation and aggregation associated with traditional buffers while maintaining pH control through alternative mechanisms.
Solution Approach 2:
The patent changes the formulation parameters by using specific concentrations of adalimumab (90-110 mg/ml) and adjusting ionic strength with salts to achieve both pH control and reduced protein instability, avoiding the harmful effects of traditional buffers.
3Quantity of substance
If high concentration adalimumab (90-110 mg/ml) is formulated, then dosage efficiency is improved, but formulation stability becomes more challenging
Solution Approach 1:
The patent achieves high concentration formulation (90-110 mg/ml) by modifying key parameters: eliminating buffers, optimizing salt concentrations (5-25 mM), using specific polyols (180-300 mM), and adjusting polysorbate levels. These parameter changes enable both high concentration and stability.
Solution Approach 2:
The formulation uses a composite approach combining adalimumab with specific ratios of salts, polyols, and surfactants to create a stable high-concentration system that leverages the synergistic effects of multiple components.
4Device complexity
If buffer-free formulations are used, then formulation simplicity is improved, but maintaining stability without buffers becomes difficult
Solution Approach 1:
The adalimumab protein and accompanying excipients serve the dual function of both formulation components and stability agents, eliminating the need for separate buffer systems while maintaining formulation stability through optimized concentrations.
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 exhibits good stability and reduces the risk of fragmentation and aggregation, while minimizing the impact of plastic leaching from single-use manufacturing components, maintaining stability for at least 6 months.
Implementation Method 1
180 mM to 300 mM of a polyol
Implementation Method 2
5 mM to 25 mM of a salt
Implementation Method 3
0.1% (w/v) of a polysorbate
Data Source
Figure 1
AI summary
A pharmaceutical composition comprises a buffer-less aqueous formulation of adalimumab, a salt, a polyol, and a polysorbate. The formulation is suitable for injection.