CD147 Monoclonal Antibody Formulation Stability
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Solution Overview
Problem
Monoclonal anti-CD147 antibodies are prone to instability due to aggregation, leading to undesired immunological reactions and safety concerns in liquid formulations, necessitating stable and quality-consistent pharmaceutical formulations.
Innovation Solution
A stable pharmaceutical formulation comprising a monoclonal anti-CD147 antibody, a buffer, a protein protective agent, and a surfactant, specifically using a histidine buffer, sucrose as the protein protective agent, and polysorbate 80 as the surfactant, with a concentration range and pH optimized for stability, including a method for preparation involving ultrafiltration and solvent exchange.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid formulation of monoclonal antibodies is used, then ease of administration is improved, but aggregation occurs leading to instability and safety concerns
Solution Approach 1:
The patent introduces excipients (surfactants like polysorbate 80, stabilizers like sucrose or trehalose, and buffers) as intermediary substances that mediate between the antibody and the liquid environment. These additives prevent aggregation by reducing surface tension, providing steric stabilization, and maintaining optimal pH, thereby enabling stable liquid formulations suitable for administration.
Solution Approach 2:
The patent optimizes multiple formulation parameters including pH (adjusted to 5.0-7.0 using buffers), temperature (storage at 2-8°C), concentration of excipients (surfactant at 0.01-0.5%, stabilizer at 1-100 mM), and ionic strength to achieve a parameter space where the antibody remains stable in liquid form without aggregating, thus resolving the contradiction between ease of administration and stability.
2Productivity
If antibody concentration is increased to reduce dosing volume, then productivity is improved, but aggregation risk increases leading to decreased reliability
Solution Approach 1:
The patent uses surfactants and stabilizers as intermediary substances that become increasingly important at higher antibody concentrations. These additives prevent intermolecular interactions that lead to aggregation, enabling the formulation to maintain reliability even as concentration increases to improve dosing efficiency.
Solution Approach 2:
The patent creates a composite formulation system where the monoclonal antibody is combined with multiple excipients (surfactants, stabilizers, buffers) in specific ratios. This composite material approach allows the formulation to achieve both high concentration (for productivity) and high stability (for reliability) by leveraging the synergistic effects of different components.
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 maintains stability over long periods, remains uniform, and retains functional activity, with the antibody remaining effective and safe for administration, as demonstrated by various stability tests.
Implementation Method 1
a buffer, a protein protective agent and a surfactant, specifically using a histidine buffer
Implementation Method 2
sucrose as the protein protective agent
Implementation Method 3
polysorbate 80 as the surfactant
Data Source
AI summary
Disclosed is a pharmaceutical preparation comprising a CD147 monoclonal antibody, a buffer, a protein protectant and a surfactant. The pharmaceutical preparation can maintain the stability of the CD147 monoclonal antibody over a long period of time. Also disclosed are the use of the pharmaceutical preparation in the preparation of a drug for treating CD147-related diseases, in particular non-small cell lung cancer, and a method for preparing the pharmaceutical preparation.