High-Concentration Antibody Formulation With Low Viscosity Stability
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Solution Overview
Problem
Existing formulations of high-concentration pharmacologically active antibodies face issues with aggregation, viscosity, and instability, which affect their stability, shelf-life, and delivery, particularly for subcutaneous administration.
Innovation Solution
A stable liquid formulation comprising pharmacologically active antibodies, such as Omalizumab, is developed using phosphate buffer, aggregation inhibitors like Arginine or Lysine, and a surfactant like Poloxamer 188, maintained at pH 6.0 to 7.0, to prevent aggregation and maintain low viscosity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If antibody concentration is increased to more than 100mg/ml for subcutaneous administration, then administration time is reduced and patient convenience is improved, but viscosity increases making injection difficult
Solution Approach 1:
The patent applies parameter changes by optimizing the pH of the formulation to a specific range (pH 5.5-6.5) and controlling ionic strength through buffer selection and concentration. These parameter adjustments reduce protein-protein interactions at high concentrations, thereby maintaining lower viscosity and improving injectability while preserving the high concentration (≥100mg/ml) needed for rapid subcutaneous administration.
2Quantity of substance
If antibody concentration is increased to more than 100mg/ml, then formulation volume is reduced for convenient home administration, but protein-protein interaction increases leading to aggregation and instability
Solution Approach 1:
The patent employs intermediary substances including specific buffers (phosphate, citrate, acetate) and surfactants (polysorbate 20, polysorbate 80, poloxamer 188) that mediate between the high concentration antibodies and prevent direct protein-protein interactions. These intermediaries stabilize the formulation by reducing aggregation and maintaining monomeric antibody structures throughout the shelf life.
3Productivity
If high concentration antibody formulation is prepared, then subcutaneous administration becomes feasible with shorter injection time, but aggregation and oligomerization occur reducing therapeutic stability
Solution Approach 1:
The patent utilizes parameter changes by precisely controlling pH (5.5-6.5), ionic strength, and excipient concentrations to create a formulation environment that suppresses aggregation. This allows the maintenance of high antibody concentration (≥100mg/ml) needed for rapid subcutaneous injection while preserving antibody monomer stability and preventing oligomerization during storage and administration.
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 stability, low aggregation, and suitable viscosity, enabling effective subcutaneous delivery with prolonged shelf-life and reduced immunogenicity.
Implementation Method 1
phosphate buffer
Implementation Method 2
suitable aggregation inhibitor selected from Arginine or suitable salt thereof
Implementation Method 3
surfactant is Poloxamer 188
Data Source
AI summary
The present disclosure describes pharmaceutically stable high concentration liquid formulations of antibody. Such formulations comprise, in addition to the antibody, at least one anti-aggregating agent selected from arginine or lysine, buffer and poloxamer 188. In addition, the present disclosure provides high concentrated antibody formulation having high monomer, low aggregates and desirable viscosity.