Mirikizumab Formulation Stability and Viscosity Control
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Solution Overview
Problem
Formulating therapeutic antibodies, such as anti-IL-23p19 antibodies, into aqueous pharmaceutical formulations suitable for subcutaneous, intramuscular, and intraperitoneal administration is challenging due to stability and viscosity issues, which affect their therapeutic efficacy and patient tolerance.
Innovation Solution
A pharmaceutical formulation comprising 50 mg/mL-150 mg/mL of IL-23p19 antibody, 8 mM-12 mM citrate buffer, 100-200 mM sodium chloride, and 0.01%-0.05% w/v surfactant, with a pH between 5.0 and 6.0, specifically optimized to maintain stability and reduce injection-associated pain.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentrations of therapeutic antibodies (50-150 mg/mL) are formulated, then the therapeutic efficacy and patient convenience are improved, but the stability and viscosity of the formulation deteriorate
Solution Approach 1:
The patent applies parameter changes by systematically optimizing pH (5.0-6.0), ionic strength (100-200 mM NaCl), and surfactant concentration (0.01%-0.05% w/v) to achieve high antibody concentrations (50-150 mg/mL) while maintaining formulation stability. This resolves the contradiction by adjusting physical-chemical parameters to simultaneously enable high concentration and stability.
Solution Approach 2:
The patent introduces surfactants as intermediary substances to mediate between high antibody concentration and formulation stability. The surfactants prevent aggregation and maintain solubility of the antibody at high concentrations, acting as a protective intermediary that enables both high concentration and stability.
2Quantity of substance
If high concentrations of therapeutic antibodies (50-150 mg/mL) are formulated, then the therapeutic efficacy and patient convenience are improved, but the viscosity increases which negatively affects administration
Solution Approach 1:
The patent changes physical parameters including pH (5.0-6.0), ionic strength (100-200 mM NaCl), and temperature to optimize viscosity. By adjusting these parameters, the formulation achieves high antibody concentration while maintaining acceptable viscosity for subcutaneous, intramuscular, and intraperitoneal administration.
Solution Approach 2:
Surfactants are introduced as intermediary substances that reduce intermolecular interactions between antibodies, thereby reducing viscosity. These surfactants act as mediators that enable high concentration formulations to maintain low enough viscosity for easy patient self-administration.
3Quantity of substance
If high concentrations of therapeutic antibodies are formulated, then the therapeutic efficacy is improved, but the rates of antibody degradation, aggregation, and other degradation processes increase
Solution Approach 1:
The patent systematically optimizes multiple parameters including pH (5.0-6.0), ionic strength (100-200 mM NaCl), and surfactant concentration (0.01%-0.05% w/v) to create a formulation environment that stabilizes antibodies at high concentrations. These parameter changes reduce degradation rates and prevent aggregation, maintaining reliability.
Solution Approach 2:
Surfactants serve as protective intermediaries that coat antibody molecules, preventing intermolecular aggregation and degradation. This intermediary layer protects the antibodies from degradation processes while maintaining high concentration, thereby improving reliability.
4Quantity of substance
If high concentrations of therapeutic antibodies are formulated, then the therapeutic efficacy is improved, but injection-associated pain increases which reduces patient tolerance
Solution Approach 1:
The patent optimizes pH (5.0-6.0) and ionic strength (100-200 mM NaCl) to reduce injection-associated pain. By adjusting these parameters, the formulation maintains high antibody concentration while minimizing pain upon injection, thereby improving patient tolerance.
Solution Approach 2:
Surfactants act as intermediaries that reduce surface tension and improve solution properties, thereby reducing injection-associated pain. These intermediaries enable high concentration formulations to be better tolerated by patients during administration.
Data Source
AI summary
Stable pharmaceutical formulations for therapeutic anti-IL-23p19 antibodies and methods of using such stable pharmaceutical formulations.