Stable Aflibercept Formulations Without Buffers
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Solution Overview
Problem
There is a need for stable liquid formulations of aflibercept suitable for ophthalmic administration, as existing formulations lack stability and effectiveness for this application.
Innovation Solution
The development of stable aqueous formulations of aflibercept, including buffer-free, organic co-solvent-free, and buffer-free and organic co-solvent-free formulations, with specific pH ranges and stabilizers such as amino acids and sugars, to maintain the protein's stability and activity for ophthalmic use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing aflibercept formulations are used, then the product is available for commercial use, but the formulations lack stability and effectiveness for ophthalmic administration
Solution Approach 1:
The patent applies parameter changes by optimizing pH ranges (5.5-7.0), adjusting stabilizer concentrations (0.1-5% w/v), and controlling ionic strength to achieve stable aqueous formulations of aflibercept specifically suitable for ophthalmic administration. These parameter optimizations resolve the contradiction between general availability and ophthalmic suitability.
2Object-affected harmful factors
If buffer-free and organic co-solvent-free formulations are developed, then safety and purity are improved, but formulation complexity increases
Solution Approach 1:
The patent removes harmful buffers and organic co-solvents from the formulation, extracting only the essential components (aflibercept, water, and minimal stabilizers). This extraction approach eliminates harmful factors while keeping the formulation simple and suitable for ophthalmic use.
3Productivity
If high concentration aflibercept formulations are prepared, then dosage efficiency is improved, but protein aggregation and particulate formation increase
Solution Approach 1:
The patent introduces stabilizers (amino acids, sugars, or polyols) as intermediary substances that mediate between high aflibercept concentrations and protein stability. These stabilizers prevent aggregation and particulate formation while allowing high concentrations (1-200 mg/mL) to maintain dosage efficiency.
Data Source
AI summary
A stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of aflibercept, wherein the formulation is free of organic co-solvent and/or free of buffer; methods for making such a formulation; and methods of using such a formulation.