Excipient Compounds for Protein Formulation Viscosity
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Solution Overview
Problem
Current protein formulations face challenges with high viscosity and stability issues, particularly at high protein concentrations, which complicates subcutaneous or intramuscular delivery and limits shelf life.
Innovation Solution
The use of liquid formulations containing a protein and an excipient compound such as hindered amines, anionic aromatics, functionalized amino acids, or low molecular weight aliphatic polyacids, which are added in a viscosity-reducing amount to improve stability and reduce viscosity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentration of protein is used to deliver high dose level, then dosage requirement is met, but viscosity rises dramatically
Solution Approach 1:
The patent introduces excipient compounds as intermediary substances that mediate between the protein molecules and the solvent. These excipients (such as surfactants, polymers, or small molecules) insert themselves between protein molecules, preventing direct protein-protein interactions that lead to clustering and high viscosity. This allows high concentration delivery while maintaining acceptable viscosity levels for injection.
Solution Approach 2:
The patent modifies the formulation parameters by adding specific excipient compounds that change the physical-chemical environment of the protein solution. By adjusting parameters such as ionic strength, pH, and molecular interactions through excipient addition, the formulation achieves reduced viscosity at high protein concentrations, enabling both high dosage delivery and ease of injection.
2Ease of operation
If restricted liquid volume is used for SC or IM injection, then patient compliance and comfort are improved, but dosage requirement cannot be met
Solution Approach 1:
The patent creates a concentrated protein formulation that copies the therapeutic effect of larger volumes while using minimal liquid. By achieving extremely high protein concentrations (e.g., >150 mg/mL) through excipient-mediated stabilization, the formulation delivers equivalent or superior dosages in reduced volumes (2-3 mL or less), maintaining patient compliance while meeting dosage requirements.
Solution Approach 2:
The patent fundamentally changes the concentration parameter of the formulation by using excipient compounds to enable supersaturated protein solutions. This parameter change allows delivering high dosages in small volumes, simultaneously achieving both patient compliance and dosage requirements that were previously contradictory.
3Quantity of substance
If high concentration of protein is used, then dosage requirement is met, but stability problems increase
Solution Approach 1:
The patent uses excipient compounds as protective intermediaries that form a protective environment around protein molecules. These excipients (such as sugars, polymers, or surfactants) prevent direct protein-protein interactions that lead to aggregation, precipitation, and degradation. This intermediary protection maintains protein stability even at high concentrations required for high dosage delivery.
Solution Approach 2:
The patent applies beforehand cushioning by incorporating stabilizing excipients into the formulation before protein stress occurs. These excipients pre-establish a protective matrix that cushions proteins against destabilizing forces such as concentration-induced aggregation, oxidation, or conformational changes, ensuring stability is maintained throughout storage and administration.
4Reliability
If conventional excipient combinations are used, then some stability improvement is achieved, but optimization must progress empirically
Solution Approach 1:
The patent identifies excipient compounds with universal multi-functional properties that simultaneously address multiple formulation challenges: viscosity reduction, stability enhancement, and solubility improvement. These versatile excipients can be applied across different protein therapeutics without requiring extensive empirical optimization for each specific protein, simplifying the development process while achieving reliable stability.
Data Source
AI summary
Disclosed herein are stability-enhanced formulations that comprise a therapeutic protein and a stability-improving amount of a stabilizing excipient, wherein the stabilized-enhanced formulation is characterized by an improved stability parameter in comparison to a control formulation otherwise identical to the stability-enhanced formulation but lacking the stabilizing excipient. Further disclosed herein are methods of improving stability of therapeutic formulations or improving parameters of protein-related processes.