Enhancing 6-Shogaol Bioavailability via β-Cyclodextrin Inclusion Complex: Synthesis, Characterization, and Anticancer Efficacy in Breast Cancer

6-Shogaol, a bioactive phytochemical derived from Zingiber officinale, demonstrates potent anticancer activity but is hindered by poor aqueous solubility, instability, pungent odor, and low bioavailability. This study aimed to enhance 6-Shogaol’s solubility and therapeutic efficacy through β-cyclodextrin (β-CD) inclusion complexation and evaluate its anticancer potential in breast cancer cells. Additionally, the study explores the co-formulation of 6-Shogaol with a β-CD inclusion complex of allicin to enhance cytotoxic potential. Inclusion complexes were prepared using physical mixture, kneading, solvent evaporation, and co-precipitation methods. The optimal complex (1:1 drug: β-CD ratio) was characterized by FTIR, XRD, SEM, and phase-solubility studies. Solubility, dissolution, and cytotoxicity were assessed in MCF-7 cells via MTT assay. The physical mixture method achieved the highest solubility enhancement (from 0.96 ± 0.02 to 3.14 ± 0.10 mg/mL), with drug loading (50.00% ± 0.075) and entrapment efficiency (76.05% ± 0.99). The stability constant (Kc = 2119.04 M⁻¹) confirmed robust complexation. In-vitro dissolution showed 95.26 ± 0.7% drug release within 2 hours. The β-CD complex exhibited improved cytotoxicity (IC₅₀ = 69.67 ± 2.3 µg/mL) versus the free drug (IC₅₀ = 95.66 ± 2.1 µg/mL), while the co-delivery of 6-Shogaol with allicin further enhanced cytotoxicity (IC₅₀ = 23.32 µg/mL). β-CD complexation significantly improved 6-Shogaol’s solubility, stability, and anticancer activity. The combination of 6-Shogaol and allicin β-CD complexes demonstrated enhanced cytotoxic potential, highlighting a promising phytopharmaceutical strategy for breast cancer therapy.