Viscosity-Reducing Excipients for High-Concentration Protein Formulations
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Solution Overview
Problem
Current biopolymer formulations face challenges in delivering high-dose therapeutic proteins subcutaneously or intramuscularly due to viscosity issues and stability problems, limiting their effectiveness and shelf life, and there is a need for a universal approach to reduce viscosity while maintaining protein activity.
Innovation Solution
The use of excipient compounds such as hindered amines, anionic aromatics, functionalized amino acids, oligopeptides, short-chain organic acids, and low molecular weight aliphatic polyacids to create liquid formulations that reduce viscosity by up to 90% and improve stability, allowing for more effective delivery and storage of proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentration of antibody is used to deliver high dose level, then dosage requirement is met, but viscosity rises dramatically making it incompatible with standard delivery systems
Solution Approach 1:
The patent introduces viscosity-reducing excipients as intermediary substances that mediate between the high concentration antibody and the delivery system. These excipients (e.g., amino acids like arginine, surfactants, or polymers) interact with the antibody molecules to reduce intermolecular interactions, thereby lowering viscosity while preserving the high dosage concentration needed for therapeutic effect
Solution Approach 2:
The patent changes the physical-chemical parameters of the antibody solution by adjusting pH, ionic strength, and temperature, and by adding specific excipients. These parameter changes modify the conformational state and interaction properties of antibodies, enabling high concentration formulations to maintain low viscosity compatible with standard SC or IM delivery systems
2Quantity of substance
If high concentration of protein is used, then dosage requirement is met, but stability problems such as precipitation, aggregation, and gel formation occur
Solution Approach 1:
The patent employs stability-enhancing excipients as intermediary substances that protect antibodies from destabilizing interactions at high concentrations. These excipients (e.g., sugars like sucrose or trehalose, polyols, or amino acids) act as molecular chaperones or osmolytes that prevent precipitation, aggregation, and gel formation, thereby maintaining formulation stability while enabling high dosage concentrations
Solution Approach 2:
The patent applies beforehand cushioning by incorporating stabilizing excipients and optimizing formulation conditions prior to storage and administration. These preemptive measures cushion against potential stability issues such as aggregation and precipitation that would otherwise occur during storage or upon concentration increase, ensuring reliable shelf life and therapeutic performance
3Ease of operation
If liquid volume is limited to 2 to 3 ccs for SC or IM injection, then patient compliance and comfort are improved, but dosage delivery is restricted
Solution Approach 1:
The patent changes the concentration parameter of the antibody formulation to enable high dosage delivery within the restricted volume. By formulating at very high concentrations (e.g., 100-500 mg/mL or higher) through advanced excipient technology and formulation methods, the patent achieves therapeutic dosage requirements in volumes suitable for comfortable SC or IM injection, thereby maintaining patient compliance while maximizing dosage delivery
Data Source
AI summary
Disclosed herein are methods for improving a parameter of a protein-related process comprising providing a viscosity-reducing excipient compound selected from the group consisting of hindered amines, anionic aromatics, functionalized amino acids, oligopeptides, short-chain organic acids, and low molecular weight aliphatic polyacids, and adding a viscosity-reducing amount of the viscosity-reducing excipient compound to a carrier solution for the protein-related process, wherein the carrier solution contains a protein of interest, and carrier solutions comprising a liquid medium in which is dissolved a protein of interest, and a viscosity-reducing excipient, wherein the viscosity of the carrier solution has a lower viscosity that that of a control solution that is substantially similar to the carrier solution except for the presence of the viscosity-reducing excipient.