Oral Bioavailability Enhancement of Docetaxel by Preparation of Freeze-Dried Ternary Solid Dispersion Using Hydrophilic Polymer and Surfactant

PurposeThe poor solubility and permeability of docetaxel have limited its oral delivery. The current study was aimed at formulating the ternary solid dispersion of docetaxel for treatment of breast cancer and evaluating its oral bioavailability.MethodsThe solid dispersions of docetaxel were prepared in drug:polymer:surfactant ratio of 1:1:0.01 by using different hydrophilic polymers namely, PVP K-30, HPMC E5, PEG 4000, PEG 10000, Eudragit EPO and Eudragit L100, with the surfactant, sodium lauryl sulphate by the technique of freeze-drying. The best polymer was then selected based on drug release data and its ratio with the drug, and surfactant was optimized.ResultsAmong the screened polymers, Eudragit L100 has given the best results in terms of aqueous solubility and dissolution. The drug:polymer:surfactant ratio for optimized dispersion was 1:3:0.01. The amorphous state of the dispersion was confirmed by solid-state analytical techniques. Enhanced drug release along with enhanced in vitro anticancer activity in the MCF-7 cell line was seen in formulated amorphous dispersion. The results of in vivo pharmacokinetic studies also revealed similar findings where the maximum plasma drug concentration (C-max), area under curve (AUC) and absorption rate constant (K-a) of dispersion were increased by 5.14, 6.46 and 1.91 times, respectively, as compared to pure drug.ConclusionThe optimized dispersion formulation DEL1003 has shown 2.68 times greater drug release due to its amorphous nature, reduced particle size to 137.7 nm and raised aqueous solubility to 274.38 mu g/ml. All these beneficial pharmaceutical factors resulted in the significant enhancement in the oral bioavailability of docetaxel. Altogether, the formulated ternary solid dispersion prepared by freeze-drying technology was found to be a promising approach for enhancing the oral delivery of docetaxel against breast neoplasm.