Antibody Formulation Surfactant Composition for Particle Reduction
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Solution Overview
Problem
The formation of particles, including aggregates, in antibody-containing formulations is a challenge, particularly for anti-coagulation factor IXa/X and anti-IL-6 receptor antibodies, where the effect of surfactant hydrophobicity and surface tension on particle formation is not well understood, necessitating improved surfactants to control particle formation.
Innovation Solution
The use of poloxamers with specific long polypropylene oxide blocks and high hydrophobicity, such as poloxamer 188, in formulations containing specific antibodies, is effective in reducing particle formation through precise HPLC conditions and surfactant properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-generated harmful factors
If conventional surfactants (poloxamer 188, polysorbates) are used to reduce particle formation, then particle formation is reduced to some extent, but the ability to reduce particle formation varies depending on surfactant type and grade, and polymer structure heterogeneity affects effectiveness
Solution Approach 1:
The patent changes the key parameters of the surfactant by specifying precise molecular weight ranges (6,840-9,510 Da), hydrophobicity ratios (0.01-0.15), and structural composition (polypropylene oxide block length). This parameter optimization ensures consistent and reliable particle formation reduction across different batches, resolving the reliability issue caused by conventional surfactant variability.
Solution Approach 2:
The patent focuses on the specific local structure of the surfactant molecule, particularly the polypropylene oxide block length and hydrophobicity distribution. By controlling the local quality of the surfactant structure (specific molecular weight distribution and hydrophobicity ratio), the patent achieves consistent particle reduction effectiveness without the heterogeneity problems of conventional surfactants.
2Object-generated harmful factors
If surfactants with high hydrophobicity are used to control particle formation, then particle formation is reduced, but the surface tension and impurity content of the surfactant affect the effectiveness
Solution Approach 1:
The patent establishes precise parameter ranges for surfactant hydrophobicity (0.01-0.15), molecular weight (6,840-9,510 Da), and impurity content (<0.1%). By controlling these parameters during manufacturing, the patent ensures both high particle reduction effectiveness and manufacturing precision, resolving the contradiction between efficacy and purity control.
Solution Approach 2:
The patent incorporates quality control measures with specified detection methods and acceptance criteria for surfactant purity and surface tension. This feedback mechanism ensures that only surfactants meeting the precise specifications are used, maintaining both high effectiveness and manufacturing precision throughout production.
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
This approach significantly reduces particle formation, ensuring stable pharmaceutical formulations by maintaining a low surface tension and controlled hydrophobicity, thereby enhancing the stability and efficacy of antibody-containing solutions.
Implementation Method 1
the effects of the surface tension of the solution containing the surfactant on particle formation were not known
Implementation Method 2
the degree of hydrophobicity of the surfactant would reduce particle formation
Data Source
AI summary
Provided is a pharmaceutical formulation with reduced particle formation, comprising an anti-coagulation factor IXa/X antibody (bispecific monoclonal antibody) that substitutes for coagulation factor VIII, or an anti-IL-6 receptor antibody that inhibits binding to the interleukin 6 receptor. Provided is a pharmaceutical formulation comprising an aqueous solution comprising a polyoxyethylene polyoxypropylene glycol (poloxamer),wherein the poloxamer is represented by formula I:wherein a and c are independently an integer selected from 75 to 85;b is an integer selected from 22 to 33; anda, b and c are average values over the entire poloxamer,and,the poloxamer comprises poloxamer molecules comprising 34 or more (C3H6O) in the molecule at a ratio of 3% (w/w) or more of the total poloxamer.