Viscosity-Reducing Excipients for Concentrated Protein Formulations
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Solution Overview
Problem
Highly concentrated protein solutions face challenges due to increased viscosity, leading to difficulties in manufacturing and administration, including protein instability, prolonged processing times, and adverse effects on process economics, with existing excipients often causing stability issues or pain during injection.
Innovation Solution
A liquid composition comprising a protein combined with specific viscosity-reducing excipients such as cyanocobalamin, pyridoxine, ascorbic acid, and thiamine derivatives, along with additional excipients like valine and arginine, to reduce viscosity and enhance stability, thereby improving the handling and administration of protein therapeutics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentration protein formulations are used to reduce injection volume, then therapeutic efficacy is improved, but viscosity increases making injection difficult
Solution Approach 1:
The patent introduces specific excipients (amino acids like arginine, lysine, histidine, proline, and their salts) as intermediary substances that mediate between the high concentration protein and the aqueous environment. These excipients interact with the protein molecules to reduce intermolecular interactions, thereby reducing viscosity and improving injectability while maintaining high protein concentration
2Ease of operation
If viscosity reducing excipients are added to high concentration protein formulations, then injectability is improved, but protein stability may be compromised
Solution Approach 1:
The patent systematically evaluates and optimizes multiple parameters including excipient type, concentration, pH, and ionic strength to find the optimal formulation space. By changing these parameters, the patent achieves a balance where viscosity is reduced sufficiently for injection while protein stability is maintained through careful selection of physiologically compatible excipients at optimized concentrations
3Stability of the object's composition
If standard excipients like sucrose and sodium chloride are used to stabilize protein formulations, then protein stability is improved, but injection pain and tissue damage increase
Solution Approach 1:
The patent replaces traditional excipients (sucrose, sodium chloride) with amino acid-based excipients that are naturally compatible with biological systems. These amino acid excipients provide stabilization functionality while being less harsh on tissues, reducing injection pain and tissue damage. The patent specifically identifies amino acids and their salts as superior alternatives to conventional excipients
4Manufacturing precision
If highly viscous protein solutions are processed through ultrafiltration and sterile filtration, then purification is achieved, but process time increases and product loss occurs
Solution Approach 1:
The patent applies viscosity-reducing excipients to the protein formulation before the purification process begins. This preliminary action reduces the viscosity of the feed solution, which subsequently reduces back pressure and shear stress during ultrafiltration and sterile filtration, leading to faster processing times and reduced product loss while maintaining purification quality
Data Source
AI summary
The present invention relates to liquid compositions and formulations comprising a protein having a reduced viscosity and/or increased stability. Furthermore, the invention relates to methods for reducing the viscosity and/or increasing the stability of a protein solution.