Buffer Solubility Prediction Method for High Salt Concentrations

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Solution Overview

Problem

Current methods fail to accurately predict the solubility of buffer solutions containing weak acid and weak base species, especially in the presence of high salt concentrations, which is crucial for preparing stable buffer stock solutions without precipitation.

Innovation Solution

A method that iteratively calculates the concentrations of ionic species in an aqueous buffer solution using dissociation equilibria and solubility products, considering the activity of ions and ionic strength, to determine solubility limits and adjust the total solute concentration accordingly.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If high salt concentrations are used in buffers for bioprocess separations, then buffering capacity and ionic strength are improved, but solubility prediction accuracy deteriorates and precipitation risk increases

Engineering Contradiction:
Improvesalt concentrationVSAvoidsolubility prediction accuracy
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The method dynamically adjusts calculation parameters including activity coefficients and solubility products based on the specific combination of ionic species and their concentrations. By changing the parameters adaptively rather than using fixed values, the system maintains accurate solubility predictions even at high salt concentrations where simple models fail.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The method employs an iterative calculation process where solubility predictions are continuously refined based on the actual ionic species concentrations and their interactions. The system feeds back the calculated activities and solubility products to adjust the total solute concentration determination, ensuring accurate predictions despite complex interactions at high salt concentrations.

Inventive Principle:
Principle #23Feedback

2Adaptability or versatility

If complex buffer formulations with multiple weak acids and bases are used, then buffer region coverage is improved, but calculation complexity increases

Engineering Contradiction:
Improvebuffer region coverageVSAvoidcalculation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The method segments the buffer system into individual ionic species and their specific interactions. By analyzing each weak acid-base pair and their respective dissociation equilibria separately, then combining the results, the system can handle complex multi-component buffers without becoming computationally intractable. This modular approach maintains versatility while managing complexity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The method uses a universal calculation framework based on dissociation equilibria and activity coefficients that applies to all weak acid-base pairs regardless of their specific chemical identities. This universal approach allows the same algorithm to handle single-component buffers, multi-component buffers, and high-salt conditions without requiring separate specialized calculations for each case.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If iterative calculation methods are used to account for ion activities, then solubility prediction accuracy is improved, but computational time increases

Engineering Contradiction:
Improvesolubility prediction accuracyVSAvoidcomputational time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The method performs iterative calculations only to the extent necessary to achieve convergence on accurate solubility predictions. By stopping the iteration process once the calculated activities and solubility products stabilize within acceptable tolerances, the system achieves high accuracy without unnecessary computational time expenditure. This partial action approach balances precision with efficiency.

Inventive Principle:
Principle #16Partial or excessive action

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

Enables reliable prediction of buffer solubility, allowing for the preparation of highly concentrated buffer solutions with controlled pH and ionic strength, reducing the risk of precipitation and optimizing buffer formulation and dilution systems.

Implementation Method 1

calculating the concentrations of all ionic species present in the buffer at the specified pH value from the total composition of the buffer and available dissociation constants

Methodology Applied
Scientific EffectDissociation equilibrium: Electrolyte

Implementation Method 2

calculating the solubility limits of each combination of ionic species present in the buffer from available solubility products

Methodology Applied
Scientific EffectSolubility product: Precipitation

Implementation Method 3

the activities of the ions are taken into account

Methodology Applied
Scientific EffectIonic strength: Electrolyte

Data Source

PatentEP3201618B1Method for predicting the solubility of a buffer
Publication Date: 2022.04.13 CYTIVA SWEDEN AB
  • EP3201618B1 patent drawingFigure 1a~1b
  • EP3201618B1 patent drawingFigure 2
  • EP3201618B1 patent drawingFigure 3

AI summary

The invention discloses a method for predicting the solubility of at least one species at a specified pH value in an aqueous buffer comprising at least one weak acid species and/or at least one weak base species. The method comprises the steps of: a) selecting a start composition of the buffer, giving a start value for the total solute concentration; b) calculating the concentrations of all ionic species present in the buffer at the specified pH value from the total composition of the buffer and available dissociation constants; c) calculating the solubility limits of each combination of ionic species present in the buffer from available solubility products, taking the concentrations calculated in step a) into account; d) comparing the concentrations of all ionic species calculated in step a) with the solubility limits calculated in step b) and determining if any solubility limit is exceeded; e) if no solubility limit is exceeded, increasing the total solute concentration of the buffer or, if at least one solubility limit is exceeded, decreasing the total solute concentration of the buffer, and; f) repeating steps b) - e) until a predetermined convergence criteria is met.