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

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Abstract

Purpose

A linear solvation energy relationship (LSER) was developed to predict the partitioning of neutral chemicals from polysorbate 80 (PS 80) micelles to water. Predicted partition coefficients were converted to a concentration dependent solubilization strength of aqueous PS 80 solutions. This solubilization strength represents a key parameter to project equilibrium levels of leaching from pharmaceutical plastic materials.

Methods

To construct the LSER model equation, partition coefficients between PS 80 micelles and water were measured via a reference phase method or collected from the literature. Multiple linear regression of partition coefficients against five publicly available solute parameters was used to obtain the LSER system parameters.

Results

112 chemically diverse compounds were incorporated for LSER model regression. The model equation shows a very good fit (R2 = 0.969, SD = 0.219) for the entire dataset. The accuracy of the multi-parameter LSER model was proven to be substantially better in comparison to a single-parameter log-linear model based on the octanol-water partition coefficient.

Conclusion

PS 80 solubilization strength in water can expediently and accurately be calculated for neutral organic compounds with the proposed LSER model. LSER system parameters provide insightful chemical information with respect to solubilization in aqueous solutions of PS 80.

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was supported by Boehringer Ingelheim. The authors report no competing financial interest.

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Authors and Affiliations

  1. Department of Biopharmaceutics and Pharmaceutical Technology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany

    Adrian Benedict Strobel & Peter Langguth

  2. Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany

    Adrian Benedict Strobel & Thomas Egert

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  1. Adrian Benedict Strobel
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  2. Thomas Egert
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Correspondence to Thomas Egert.

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Strobel, A.B., Egert, T. & Langguth, P. Predicting Leachables Solubilization in Polysorbate 80 Solutions by a Linear Solvation Energy Relationship (LSER). Pharm Res 38, 1549–1561 (2021). https://doi.org/10.1007/s11095-021-03096-8

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