SUSTAINED RELEASE TABLETS OF SORAFENIB-SILIBININ COMBINATIONS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA


Savita Mishra, Sandhya Hora, Vibha Shukla, Mukul Das, Harsha Kharkwal, Deepshikha Pande Katare

Abstract


Objective: The aim of this study was to develop polymer coated sustained release tablet using sorafenib and silibinin combination for the treatment of hepatocellular carcinoma.

Methods: The qualitative analysis such as weight variation, friability, hardness, interaction studies, disintegration and in vitro release were performed to validate formulated tablets. We have maintained the acceptable official limits for weight variation, friability, hardness and disintegration time according to prescribed pharmacopoeial recommendation. In vitro drug release studies were performed using USP-II (paddle type) dissolution apparatus. The MTT assay was performed for assessment of Cell viability of drug combination for tablet formulation. Molecular docking studies have been performed to determine the combinatorial mode of action for the tablet formulation.

Results: Friability and weight variation were less than 1% for each formulation, which were within range of prescribed pharmacopoeial recommendation. The hardness of 20 tablets showed 5-6.5Kg/cm2 for all formulations 5-6.5Kg/cm2. The optimized formulation resulted in 98% drug release after 28 h. The present study reports the synergistic effects of drug combination to inhibit cell growth in HepG2 cell line. Molecular docking studies showed that sorafenib has high binding affinity for B-Raf vascular endothelial growth factor receptor β and protein kinase B. Silibinin showed binding affinity with MAP kinase-11, protein phosphatase 2 A and tankyrase.

Conclusion: The present study reports for the first time a novel formulation for sustained release and reduced toxicity of sorafenib with enhanced inhibitory effect of the drug combination on cancerous hepatic cell line as well collaborative mechanism of action for the formulation.


Keywords


Sustained release, Pullulan, Combinational treatment, Silibinin, Silymarin, Sorafenib, Hepatocellular Carcinoma

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About this article

Title

SUSTAINED RELEASE TABLETS OF SORAFENIB-SILIBININ COMBINATIONS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA

Keywords

Sustained release, Pullulan, Combinational treatment, Silibinin, Silymarin, Sorafenib, Hepatocellular Carcinoma

DOI

10.22159/ijap.2018v10i5.27597

Date

08-09-2018

Additional Links

Manuscript Submission

Journal

International Journal of Applied Pharmaceutics
Vol 10, Issue 5 (Sep-Oct), 2018 Page: 117-124

Online ISSN

0975-7058

Authors & Affiliations

Savita Mishra
Proteomics & Translational Research Lab, Centre for Medical Biotechnology, Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India
India

Sandhya Hora
Proteomics & Translational Research Lab, Centre for Medical Biotechnology, Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India

Vibha Shukla
CSIR- Indian Institute of Toxicology Research, Lucknow, India

Mukul Das
CSIR- Indian Institute of Toxicology Research, Lucknow, India

Harsha Kharkwal
Amity institute of Phytomedicine and Phytochemistry& Amity Center for Carbohydrate Research, Amity University Uttar Pradesh, Noida, India

Deepshikha Pande Katare
Proteomics & Translational Research Lab, Centre for Medical Biotechnology, Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India
India


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