Antibody Formulation Dual Buffer System Viscosity
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Solution Overview
Problem
Liquid antibody formulations face challenges due to instability caused by pH sensitivity, temperature, and oxidation, leading to rapid degradation and aggregation, which complicates their therapeutic use.
Innovation Solution
A stable liquid antibody formulation using a dual buffer system comprising phosphate and amino acids, which acts as a counter-ion, along with sorbitol and surfactant, without the need for antioxidants, maintaining low viscosity and stability across various storage conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If liquid formulations with high antibody concentrations are used, then the therapeutic efficacy is improved, but the viscosity increases and aggregation occurs
Solution Approach 1:
The patent changes the chemical parameters of the buffer system by introducing a dual buffer system comprising phosphate and amino acid components. This chemical parameter modification enables the formulation to maintain low viscosity and prevent aggregation at high antibody concentrations (10-200 mg/ml), thereby resolving the contradiction between concentration and physical stability.
2Ease of operation
If liquid formulations are used for convenience of administration, then the ease of operation is improved, but the chemical stability deteriorates due to faster degradation
Solution Approach 1:
The patent employs a composite buffer system combining phosphate and amino acid components working together. This composite approach provides synergistic protection against multiple degradation pathways (deamidation, hydrolysis, oxidation) while maintaining the liquid formulation's administrative convenience, thus resolving the contradiction between ease of operation and chemical stability.
3Object-affected harmful factors
If antioxidants are added to prevent oxidation, then the protection from oxidation is improved, but the formulation complexity increases
Solution Approach 1:
The dual phosphate-amino acid buffer system inherently provides protection against oxidation without requiring the addition of separate antioxidant agents. The buffer components themselves create a chemical environment that prevents oxidative degradation, allowing the formulation to protect itself and thereby reducing formulation complexity while maintaining oxidation protection.
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 retains high monomeric content and low aggregate levels, ensuring the antibody's stability and efficacy over extended storage periods without the use of antioxidants, even under extreme conditions.
Implementation Method 1
a stable liquid antibody formulation, wherein the antibody is formulated in a dual buffer system comprising phosphate and amino acid as the buffer
Implementation Method 2
the invention discloses a stable liquid formulation in phosphate-amino acid buffer, comprising sorbitol, surfactant, and optionally arginine
Implementation Method 3
the invention discloses a stable liquid formulation in phosphate-amino acid buffer, comprising sorbitol, surfactant, and optionally arginine
Data Source
AI summary
The present invention provides a stable liquid formulation of an antibody in phosphate-amino acid based dual buffer system. The antibody formulated in phosphate-amino acid based dual buffer system imparts optimum stability to the antibody, at lower as well as higher concentrations. Further, the antibody formulated in phosphate-amino acid based buffer system has low viscosity and is suitable for therapeutic administration of high concentrations of antibody.