Predicting the solubility of the anti-cancer agent docetaxel in small molecule excipients using computational methods

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 (delta) and Flory-Huggins interaction (chi(FH)) parameters. The delta values of docetaxel and excipients were calculated using semi-empirical methods and molecular dynamics (MD) simulations. Cerius(2) software and COMPASS force-field were employed for the MD simulations. The chi(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 beta-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.