DEVELOPMENT OF QUERCETIN-RESVERATROL IMMEDIATE RELEASE ANTICANCER TABLETS FOR THE MANAGEMENT OF BREAST CANCER BY INVESTIGATING CYTOTOXIC POTENTIAL AGAINST MCF-7 CELL LINES

Abstract

Breast cancer remains one of the most prevalent malignancies and a leading cause of cancer-related mortality among women worldwide, highlighting the need for effective and safer therapeutic approaches. The present study aimed to develop and optimize a quercetin–resveratrol immediate-release tablet for potential breast cancer management by integrating molecular docking, in vitro biological evaluation, pharmaceutical formulation, and Quality by Design (QbD)-based optimization. Molecular docking was initially performed to evaluate the interactions of selected phytoconstituents with the epidermal growth factor receptor (EGFR), identifying quercetin, resveratrol, and naringenin as promising candidates for further investigation. The antiproliferative activity of these phytoconstituents was subsequently assessed against MCF-7 breast cancer cells using the MTT assay, where quercetin and resveratrol exhibited greater cytotoxic activity than naringenin and were therefore selected for formulation development. Immediate-release tablets containing quercetin and resveratrol in different ratios (1:1, 1:2, and 2:1) were prepared using a solid dispersion approach followed by direct compression. Formulation optimization was carried out using a Box–Behnken Design to evaluate the influence of formulation variables on drug release, disintegration time, and tablet hardness. The optimized formulation demonstrated satisfactory physicochemical properties, acceptable pre- and post compression characteristics, drug–excipient compatibility, and efficient dissolution. Biological evaluation of the developed formulations using the sulforhodamine B (SRB) assay demonstrated that the quercetin: resveratrol (2:1) formulation exhibited the greatest antiproliferative activity against MCF-7 cells, with an IC₅₀ value comparable to that of gefitinib. Overall, the findings demonstrate that integrating computational screening, experimental validation, pharmaceutical formulation, and QbD-guided optimization provide a systematic strategy for developing phytoconstituent-based oral formulations and identifies the optimized quercetin–resveratrol immediate-release tablet as a promising candidate for further preclinical evaluation in breast cancer therapy.