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

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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.

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Acknowledgments

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

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Toronto, Toronto, Ontario, M5S 3M2, Canada

    Loan Huynh, Justin Grant & Christine Allen

  2. Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, Quebec, H3C 3J7, Canada

    Jean-Christophe Leroux

  3. Bioxel Pharma Inc., Quebec, G1W 4Y5, Canada

    Pascal Delmas

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  1. Loan Huynh
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  2. Justin Grant
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  3. Jean-Christophe Leroux
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  4. Pascal Delmas
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  5. Christine Allen
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Correspondence to Christine Allen.

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Huynh, L., Grant, J., Leroux, JC. et al. Predicting the Solubility of the Anti-Cancer Agent Docetaxel in Small Molecule Excipients using Computational Methods. Pharm Res 25, 147–157 (2008). https://doi.org/10.1007/s11095-007-9412-3

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