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Pharmaceutical Research

, Volume 25, Issue 1, pp 147–157 | Cite as

Predicting the Solubility of the Anti-Cancer Agent Docetaxel in Small Molecule Excipients using Computational Methods

  • Loan Huynh
  • Justin Grant
  • Jean-Christophe Leroux
  • Pascal Delmas
  • Christine Allen
Research Paper

Abstract

Purpose

To develop an in silico model that provides an accurate prediction of the relative solubility of the lipophilic anticancer agent docetaxel in various excipients.

Materials and Methods

The in silico solubility of docetaxel in the excipients was estimated by means of the solubility (δ) and Flory-Huggins interaction (χ FH) parameters. The δ values of docetaxel and excipients were calculated using semi-empirical methods and molecular dynamics (MD) simulations. Cerius2 software and COMPASS force-field were employed for the MD simulations. The χ FH values for the binary mixtures of docetaxel and excipient were also estimated by MD simulations.

Results

The values obtained from the MD simulations for the solubility of docetaxel in the various excipients were in good agreement with the experimentally determined values. The simulated values for solubility of docetaxel in tributyrin, tricaproin and vitamin E were within 2 to 6% of the experimental values. MD simulations predicted docetaxel to be insoluble in β-caryophyllene and this result correlated well with experimental studies.

Conclusions

The MD model proved to be a reliable tool for selecting suitable excipients for the solubilization of docetaxel.

Key words

docetaxel excipients Flory-Huggins interaction parameter molecular dynamics simulations solubility parameters 

Notes

Acknowledgments

The authors are grateful to Natural Sciences and Engineering Research Council (NSERC) for funding this research.

Supplementary material

11095_2007_9412_MOESM1_ESM.doc (78 kb)
ESM 1 (DOC 78.0 KB)

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Loan Huynh
    • 1
  • Justin Grant
    • 1
  • Jean-Christophe Leroux
    • 2
  • Pascal Delmas
    • 3
  • Christine Allen
    • 1
  1. 1.Faculty of PharmacyUniversity of TorontoTorontoCanada
  2. 2.Canada Research Chair in Drug Delivery, Faculty of PharmacyUniversity of MontrealQuebecCanada
  3. 3.Bioxel Pharma Inc.QuebecCanada

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