Protein Formulation Stabilization with Polysorbate 80 and Arginine
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Solution Overview
Problem
There is a challenge in formulating high concentration antibody formulations, particularly for subcutaneous administration, as increasing protein concentration can lead to issues such as protein aggregation, degradation, solubility, stability, and viscosity, along with manufacturing and supply chain difficulties.
Innovation Solution
A pharmaceutical formulation comprising a protein with an antigen binding domain that binds to VEGF-B, an organic acid buffer, a non-ionic surfactant, and at least one amino acid stabilizer, which maintains stability, solubility, and suitable viscosity for injection without the need for additional salts or stabilizing agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentration of protein is used in formulation, then injection volume is reduced, but protein aggregation and degradation increase
Solution Approach 1:
The patent introduces specific excipients (polysorbate 80, arginine, histidine buffer) as intermediary substances that mediate between the high protein concentration requirement and protein stability requirement. These excipients act as protective agents that prevent aggregation and degradation while allowing high concentration formulation.
Solution Approach 2:
The patent changes the chemical parameters of the formulation by adjusting pH (using histidine buffer to maintain pH 5.0-6.0), adding surfactants (polysorbate 80 at 0.01-0.1%), and incorporating amino acid stabilizers (arginine at 50-150 mM). These parameter changes enable high concentration formulations to maintain protein stability.
2Quantity of substance
If high concentration of protein is used in formulation, then injection volume is reduced, but viscosity increases
Solution Approach 1:
The patent uses polysorbate 80 as a surfactant intermediary that reduces the viscosity increase caused by high protein concentration. The surfactant acts as a mediator that maintains fluidity while allowing high protein loading, making the formulation suitable for subcutaneous injection.
3Reliability
If additional salts and stabilizing agents are added to formulation, then protein stability improves, but formulation complexity increases
Solution Approach 1:
The patent selects excipients that perform multiple functions simultaneously. For example, arginine serves both as a stabilizing agent preventing aggregation and as a viscosity modifier. The histidine buffer provides both pH control and stability. This multi-functionality reduces the number of separate components needed while maintaining protein stability.
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 high protein concentrations (up to 220 mg/mL) while maintaining stability and suitable viscosity, addressing the challenges of protein aggregation and degradation, and ensuring long-term stability at various temperatures.
Implementation Method 1
a non-ionic surfactant
Implementation Method 2
an organic acid buffer, wherein the formulation has a pH of 5.0 to 6.0
Implementation Method 3
at least one amino acid stabiliser
Data Source
AI summary
The present disclosure is directed to a liquid formulation comprising high concentration of a protein comprising an antigen binding domain that binds to VEGF-B, an organic buffer, a non-ionic surfactant and an amino acid stabilizer, wherein the pH of the formulation is 5.0-6.5. The formulation comprises a histidine buffer, a polysorbate 80 surfactant and the amino acid stabilizers arginine and proline.