Evaluation of Two Cosolvency Models to Predict Solute Partitioning between Polymers (LDPE) and Water - Ethanol...

Area of Science:

• Pharmaceutical Science
• Materials Science
• Analytical Chemistry

Background:

• Plastic materials in pharmaceutical applications can leach chemicals into drug products.
• Accurate estimation of patient exposure to leached chemicals is crucial for safety assessments.
• Simulating the extraction strength of clinical media is key for reliable leaching studies.

Purpose of the Study:

• To develop a quantitative method for tailoring the extraction strength of water-ethanol mixtures.
• To mimic the polarity-driven extraction strength of clinically relevant media.
• To improve the accuracy of patient exposure estimations from pharmaceutical plastic materials.

Main Methods:

• Calculated hypothetical partition coefficients using log-linear and linear solvation energy relationship (LSER) cosolvency models.
• Employed a thermodynamic cycle with LDPE/water partition coefficients to predict partitioning in water-ethanol mixtures.
• Experimentally verified calculated partition coefficients for diverse chemical solutes.

Main Results:

• Calculated partition coefficients between LDPE and water-ethanol mixtures showed good correlation with experimental values.
• The LSER-based model demonstrated slightly superior predictive accuracy compared to the log-linear model.
• The developed models enable accurate prediction of solute partitioning into simulating solvent mixtures.

Conclusions:

• Cosolvency models combined with LSER-predicted partition coefficients allow tailored preparation of water-ethanol simulating mixtures.
• This approach enhances the reliability of patient exposure estimations for pharmaceutical plastic materials.
• Optimized extraction profiles reduce time and resources for chemical safety risk assessments.