Buffer-Less 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, as existing formulations often include buffers that can adversely affect stability and shelf-life, and there is a lack of effective buffer-less alternatives.
Innovation Solution
A pharmaceutical composition comprising pharmaceutical-grade water with 90-110 mg/ml adalimumab, 5-25 mM salt, 180-300 mM polyol, and 0.1% polysorbate, without additional buffers, to provide stability and suitability for subcutaneous injection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If buffer systems (citrate/phosphate) are added to adalimumab formulations, then pH stability is improved, but formulation complexity and potential stability issues increase
Solution Approach 1:
The patent removes the buffer system from the adalimumab formulation entirely, relying on the self-buffering capacity of the antibody molecule itself. This extraction of the buffer component simplifies the formulation while maintaining pH stability through the protein's intrinsic properties.
Solution Approach 2:
The adalimumab antibody serves its own buffering needs through its amino acid residues, eliminating the requirement for external buffer additives. The protein's side chains provide the necessary pH buffering capacity without requiring additional chemical components.
2Stability of the object's composition
If buffer additives are included in adalimumab formulations, then pH control is improved, but shelf-life and stability are adversely affected
Solution Approach 1:
By removing buffer additives from the formulation, the patent eliminates the stability issues and shelf-life reductions associated with buffer-protein interactions, while maintaining adequate pH control through the antibody's self-buffering capacity.
3Quantity of substance
If high concentration adalimumab (100 mg/ml) is formulated, then dosage efficiency is improved, but stability and aggregation risks increase
Solution Approach 1:
The removal of buffer systems eliminates buffer-induced aggregation and stability issues that typically plague high-concentration formulations, enabling the 100 mg/ml concentration to be achieved without the usual stability compromises.
Solution Approach 2:
The patent changes the formulation parameters by eliminating buffers and adjusting excipient concentrations, which allows high antibody concentration to be maintained without the usual increase in aggregation and stability problems.
4Stability of the object's composition
If multiple excipients (buffers, stabilizers, surfactants) are added, then formulation stability is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent removes buffer components from the formulation, reducing the number of excipients that need to be sourced, characterized, controlled, and manufactured, thereby simplifying the manufacturing process while maintaining stability through self-buffering.
Data Source
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.