Low-Molecular-Weight PVP Formulations for High-Protein Viscosity Reduction
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Solution Overview
Problem
Highly concentrated protein formulations face challenges due to increased viscosity, which complicates manufacturing, handling, and administration, particularly for subcutaneous delivery, necessitating the need for compounds that reduce viscosity without compromising protein stability.
Innovation Solution
Incorporating low molecular weight polyvinylpyrrolidone (PVP) and arginine hydrochloride (Arg-HCl) into protein formulations at specific concentrations to achieve reduced viscosity, maintaining protein stability and facilitating easier administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If high concentration protein formulations are used to reduce dose volume, then the volume is reduced to meet subcutaneous administration requirements, but viscosity increases making handling and administration difficult
Solution Approach 1:
The patent introduces polyvinylpyrrolidone (PVP) as an intermediary substance that mediates between the high protein concentration requirement and the ease of administration requirement. PVP acts as a viscosity-modifying agent that allows the formulation to maintain high protein concentration while reducing viscosity to acceptable levels for subcutaneous injection
Solution Approach 2:
The patent changes the physical-chemical parameters of the formulation by adding PVP at specific concentrations (0.1-10% w/v). This parameter change modifies the rheological properties of the formulation, specifically reducing viscosity while maintaining protein concentration, thereby resolving the contradiction between dose volume reduction and ease of administration
2Volume of moving object
If high concentration protein formulations are used to meet subcutaneous administration requirements, then smaller dose volume is achieved, but manufacturing becomes difficult due to increased viscosity
Solution Approach 1:
PVP serves as an intermediary that facilitates manufacturing by reducing the viscosity-induced difficulties in bulk handling, filtration, and filling operations. The additive enables high-concentration formulations to be manufactured using conventional equipment and processes without requiring specialized low-viscosity handling procedures
Solution Approach 2:
By adjusting the PVP concentration parameter within the range of 0.1-10% w/v, the formulation achieves optimal viscosity for manufacturing. This parameter optimization allows standard manufacturing processes to proceed efficiently while maintaining the required high protein concentration for small dose volume
3Ease of operation
If viscosity-reducing agents are added to high concentration formulations, then ease of administration is improved, but protein stability may be compromised
Solution Approach 1:
The patent optimizes the PVP concentration parameter within a specific range (0.1-10% w/v) that balances viscosity reduction with protein stability maintenance. This parameter optimization ensures that the viscosity-modifying effect is achieved while the protein remains stable, preventing aggregation and degradation
Solution Approach 2:
The patent creates a composite formulation system combining protein and PVP where the two components work synergistically. The composite nature of this formulation allows the PVP to provide viscosity reduction while the protein maintains its structural and functional stability, resolving the contradiction between ease of administration and protein stability
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination of PVP and Arg-HCl effectively decreases viscosity by up to 80% while preserving protein stability, enabling easier handling and administration with minimal impact on protein integrity.
Implementation Method 1
the viscosity of the composition comprising the PVP is less than a composition comprising the same concentration of the therapeutic protein, but the PVP is absent
Data Source
AI summary
Disclosed herein are pharmaceutical compositions (formulations) having reduced viscosity, using a low molecular weight polyvinylpyrrolidone (povidone) in the case of high therapeutic protein concentration (≥70 mg/ml) formulations. The addition of arginine, such as arginine monohydrochloride or N-acetyl arginine, can further reduce viscosity. Appropriate therapeutic proteins include antibodies, such as monoclonal antibodies, and derivatives, fragments, and analogues thereof.