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

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Abstract

Purpose

The 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.

Methods

The 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.

Results

Among 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 (Cmax), area under curve (AUC) and absorption rate constant (Ka) of dispersion were increased by 5.14, 6.46 and 1.91 times, respectively, as compared to pure drug.

Conclusion

The 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 μg/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.

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Data Availability

All data generated or analysed during this study are included in this published article.

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Acknowledgements

The authors are highly thankful to Mr. Dhiraj Khattar and Dr. Sandip Zode, Fresenius Kabi Oncology Ltd., Gurgaon, India, for providing a free gift sample of valuable docetaxel. We also thank Dr. S.S. Chitlange, Dr. Shubhangi Shekade, DYPIPSR, Pune, India, for allowing us to use lyophilizer for freeze-drying of our formulations. The authors also express their sincere thanks to Dr. Sandip Patil, Director, Biocyte Laboratories, for supporting our in vitro anticancer activity studies and in vivo bioavailability studies in this research. We would also like to thank the professionals at Savitribai Phule Pune University, Pune ,for providing excellent facilities for the examination of solid-state samples. The authors would like to thank Dr. Amit Kasabe, Director of the Aster Analytics Research Institute in Pune, for helping us with the data interpretation.

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Authors and Affiliations

  1. University Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Maharashtra, 431004, Aurangabad, India

    Preeti Tanaji Mane & Pravin Shridhar Wakte

  2. Vilasrao Deshmukh Foundation group of Institutions, VDF School of Pharmacy, New MIDC, Airport Road, Maharashtra, 413531, Latur, India

    Balaji Sopanrao Wakure

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Contributions

Conceptualization: Mane P. T., Wakte P. S.; research methodology: Mane P. T., Wakure B. S.; formal analysis: Mane P. T., Wakure B. S.; resources: Mane P. T., Wakure B. S.; Wakte P. S.; writing-original draft: Mane P. T.; writing—review and editing: Mane P. T., Wakure B. S., Wakte P. S.

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Correspondence to Preeti Tanaji Mane.

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Ethics Approval and Consent to Participate

In accordance with the recommendations of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India, the Institutional Animal Ethics Committee (IAEC) has the approval of all animal experimental procedures (CPCSEA registration number: 1988/PO/Re/S/17/CPCSEA). The IAEC of Gourishankar Institute of Pharmaceutical Education & Research, Limb, Satara, Maharashtra, India, has the approval of all animal experimental procedures for this project number GIPER/IAEC/22/07. The authors state that for all the animal experimental studies, they have gotten the necessary institutional review board approval or have complied with the Declaration of Helsinki’s guiding principles.

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Mane, P.T., Wakure, B.S. & Wakte, P.S. Oral Bioavailability Enhancement of Docetaxel by Preparation of Freeze-Dried Ternary Solid Dispersion Using Hydrophilic Polymer and Surfactant. J Pharm Innov 18, 1669–1684 (2023). https://doi.org/10.1007/s12247-023-09746-1

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