NMP Excipient Reduces Viscosity in High-Concentration Protein Formulations
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Solution Overview
Problem
Highly concentrated protein formulations for subcutaneous administration face challenges due to increased viscosity, making them difficult to handle and inject, as they are either too thick or require larger needles, which is unpleasant for patients.
Innovation Solution
The use of N-methyl pyrrolidone (NMP) at selected concentrations, combined with other excipients like arginine, lysine, and N-acetyl arginine, to reduce the viscosity of protein pharmaceutical formulations, allowing for more stable and injectable high-concentration protein solutions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If protein concentration is increased to meet dose volume requirements for subcutaneous administration, then the dose volume can be reduced, but the viscosity of the formulation increases making it difficult to handle and inject
Solution Approach 1:
The patent applies parameter changes by adding NMP (N-methyl-2-pyrrolidone) at specific concentrations (1-1000 mM, preferably 100-500 mM) to modify the physical properties of the protein formulation. This excipient changes the solution parameters to reduce viscosity while maintaining high protein concentration (100-300 mg/mL), enabling both small dose volume and ease of injection
2Productivity
If protein concentration is increased to reduce formulation volume, then fewer injections are needed, but the formulation becomes difficult to manufacture and fill
Solution Approach 1:
The patent uses NMP as an intermediary substance that mediates between the conflicting requirements of high protein concentration and manufacturability. NMP acts as a viscosity-reducing excipient that facilitates handling during bulk processing and filling operations while allowing the formulation to maintain the high protein concentration needed for reduced injection frequency
3Quantity of substance
If protein concentration is increased to meet therapeutic dose requirements, then the treatment efficacy is maintained, but the formulation becomes difficult to administer to patients
Solution Approach 1:
The patent modifies the formulation parameters by incorporating NMP at optimized concentrations that reduce viscosity enough to enable easy syringe drawing and injection, while maintaining the high protein concentration (100-300 mg/mL) required to deliver the therapeutic dose in a small volume suitable for subcutaneous administration
Data Source
AI summary
Described herein are therapeutic protein formulations comprising N-methyl pyrrolidone (NMP), methods related to reducing viscosity of pharmaceutical formulations and methods related to stabilizing pharmaceutical formulations using NMP.