Sorbitol-PEG Protein Formulation Stability
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Solution Overview
Problem
Protein formulations, particularly antibodies like anti-HER2, face challenges in maintaining stability due to structural complexity, leading to physical and chemical degradation such as aggregation, deamidation, and oxidation, which affects bioactivity and safety, and existing stabilizers can cause compatibility issues.
Innovation Solution
A stable pharmaceutical formulation comprising an anti-HER2 antibody with a specified molar excess of sorbitol and polyethylene glycol (PEG) in defined ratios, along with buffering agents like L-histidine, to maintain structural integrity and prevent degradation, formulated for lyophilization and reconstitution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If traditional stabilizers are used to prevent protein degradation, then protein stability is improved, but compatibility issues arise with other formulation components
Solution Approach 1:
The patent changes the chemical parameters of the stabilizer by using sorbitol instead of traditional stabilizers like trehalose or mannitol. This parameter change resolves the compatibility issue while maintaining protein stability, as sorbitol does not interfere with other formulation components.
Solution Approach 2:
The patent employs sorbitol as a simple, effective stabilizer that can be easily removed or adjusted in the formulation. Its simplicity and lack of interference make it an ideal temporary stabilizer that maintains protein integrity without creating long-term compatibility problems.
2Stability of the object's composition
If additional lyoprotectants are added to maintain protein stability during lyophilization, then protein stability is improved, but formulation complexity increases
Solution Approach 1:
The patent extracts and removes unnecessary lyoprotectants like trehalose or mannitol from the formulation, retaining only sorbitol as the essential stabilizer. This extraction simplifies the formulation while maintaining protein stability during lyophilization, as sorbitol alone provides sufficient protection.
Solution Approach 2:
Sorbitol serves multiple functions simultaneously: it acts as a stabilizer during storage, a lyoprotectant during lyophilization, and a compatibility agent with other formulation components. This multi-functionality eliminates the need for multiple separate additives, reducing formulation complexity.
3Stability of the object's composition
If high concentrations of stabilizers are used to prevent aggregation, then protein aggregation is reduced, but osmotic stress on the protein increases
Solution Approach 1:
The patent changes the type of stabilizer from traditional high-osmolarity agents to sorbitol, which provides effective aggregation prevention at lower concentrations. This parameter change reduces osmotic stress on the protein while maintaining adequate stabilization, as sorbitol's molecular structure allows for effective protein shielding at moderate concentrations.
Data Source
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AI summary
A stable pharmaceutical formulation comprising a protein of interest, sorbitol and polyethylene glycol (PEG). The sorbitol and protein is present in a molar ratio of 550 to 700 mole of sorbitol: 1 mole of protein and the PEG to protein is present in the molar ratio of 2-50:1. The formulation optionally comprising buffer. The formulation in lyophilised form is stable for at least 4 years at 2-8 ° C. Also provided is a process for preparing the composition and a pharmaceutical kit comprising the same.