Adalimumab Formulation Stability via Polyol and Buffer Systems
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Solution Overview
Problem
There is a need for stable liquid formulations of adalimumab that allow long-term storage without substantial loss in efficacy, as existing formulations face challenges in maintaining the stability and effectiveness of the antibody over time.
Innovation Solution
The development of stable aqueous pharmaceutical compositions of adalimumab that include a stabilizer such as a polyol and a surfactant, along with a buffer system comprising citrate, phosphate, succinate, histidine, tartrate, or maleate, with a pH range of 4 to 8, specifically using histidine and succinate as preferred buffering agents to enhance long-term stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If adalimumab is stored in existing formulations, then it can be stored for a period of time, but it experiences substantial loss in efficacy and stability over long-term storage
Solution Approach 1:
The patent modifies the formulation parameters by incorporating specific stabilizers (polyols such as sorbitol, mannitol, or trehalose; surfactants such as polysorbate 20, polysorbate 80, or poloxamer 188) and buffers (citrate, phosphate, succinate, histidine, tartrate, or maleate) at optimized concentrations to maintain adalimumab stability during long-term storage
Solution Approach 2:
The patent creates a composite aqueous formulation system combining adalimumab with multiple excipients including stabilizers, buffers, and surfactants that work synergistically to prevent protein degradation, aggregation, and denaturation during storage
2Stability of the object's composition
If adalimumab is formulated with stabilizers and buffers for long-term storage, then stability is improved, but formulation complexity increases
Solution Approach 1:
The patent employs multi-functional excipients that simultaneously perform multiple roles: polyols provide both stabilization and osmotic balance, surfactants prevent both aggregation and surface adsorption, and buffers maintain both pH stability and ionic strength, thereby reducing the need for additional separate components
Data Source
AI summary
The invention provides aqueous pharmaceutical adalimumab compositions suitable for long-term storage of adalimumab, methods of manufacture of these compositions, methods of administration, and kits containing same.