Predicting Leachables Solubilization in Polysorbate 80 Solutions by a Linear Solvation Energy Relationship (LSER)

Area of Science:

• Physical Chemistry
• Pharmaceutical Science
• Polymer Science

Background:

• Polysorbate 80 (PS 80) is widely used in pharmaceuticals.
• Understanding chemical partitioning in PS 80 solutions is vital for drug formulation and safety.
• Leaching of chemicals from pharmaceutical packaging materials is a regulatory concern.

Purpose of the Study:

• To develop a linear solvation energy relationship (LSER) model to predict neutral chemical partitioning from PS 80 micelles to water.
• To convert partition coefficients into a concentration-dependent solubilization strength for aqueous PS 80 solutions.
• To establish a parameter for predicting equilibrium leaching levels from pharmaceutical plastic materials.

Main Methods:

• Measured partition coefficients between PS 80 micelles and water using a reference phase method and literature data.
• Employed multiple linear regression to correlate partition coefficients with five solute parameters.
• Obtained LSER system parameters for model construction.

Main Results:

• Developed an LSER model incorporating 112 diverse compounds.
• Achieved a high model fit (R² = 0.969, SD = 0.219) for the dataset.
• Demonstrated superior accuracy compared to a single-parameter log-linear model based on octanol-water partition coefficient.

Conclusions:

• The LSER model accurately and efficiently calculates PS 80 solubilization strength for neutral organic compounds.
• LSER system parameters offer valuable chemical insights into solubilization within aqueous PS 80 solutions.
• The model aids in predicting chemical leaching from pharmaceutical materials.