The incessant global burden of cancer, particularly breast cancer, drives the urgent need for innovative therapeutic strategies that improve efficacy while reducing the enfeebling side effects of conventional chemotherapy. Drug repurposing, combined with advanced pharmaceutical engineering, presents a promising avenue for rapid clinical translation. This study investigates the anti-cancer potential of a novel pharmaceutical drug-drug co-crystal (DDC) synthesised from Aspirin, a known chemo preventive agent, and Simvastatin, a statin with emerging anti-tumour properties

The co-crystal was successfully synthesised via mechanochemical grinding and thoroughly characterised. Its enhanced aqueous solubility and unique thermal profile confirmed the formation of a new solid-state phase. In vitro biological evaluation (with assays like DPPH, H₂O₂ scavenging, NO scavenging, Protein denaturation and HRBC) demonstrated superior free radical scavenging and anti-inflammatory activities compared to the parent drugs alone. Crucially, the co-crystal exhibited potent anti-proliferative effects against MCF-7 breast cancer cells, significantly reducing cell viability and migration and inducing apoptosis. The IC₅₀ values of DDC, Aspirin and Simvastatin alone were scored to be 49.3987, 68.86, 19.49 µg/ml respectively. Mechanistic insights from RT-PCR analysis revealed profound downregulation of key oncogenic markers (BCL-2, COX-2) and upregulation of the pro-apoptotic BAX gene. Furthermore, the co-crystal remained stable and bioavailable under simulated gastrointestinal conditions, supporting its potential for oral administration. Complementary molecular docking studies confirmed strong binding affinities of the parent molecules to the active sites of the target proteins, rationalising the observed biological activity.

These compelling results position the Aspirin-Simvastatin co-crystal as a highly promising candidate for breast cancer therapy. It exemplifies a rational approach to drug development by enhancing the therapeutic profile of existing drugs through crystal engineering, offering a faster and potentially safer route to novel oncology treatments.

Keywords: Drug-Drug Co-crystal, Drug Repurposing, Breast Cancer (MCF-7), Apoptosis, Molecular Docking, Bioavailability, Solid-State Chemistry.