Host–Guest System of Beta‐Cyclodextrin and Fisetin Prepared by Solvent Evaporation Method: Preparation, Characterization, Phase Solubility, In Vitro Release, and Cell Viability Activity

Abstract The purpose of the investigation was to formulate fisetin‐β‐cyclodextrin (βCD) binary inclusion complex employing solvent evaporation. A phase solubility study of fisetin was executed in the presence of βCD (2–10 mM). Fisetin‐binary inclusion complex was tested by DSC, FTIR, XRD, SEM, in vitro release, and cell viability measurements. A phase solubility test showed that fisetin solubility was elevated 4.11‐fold in the presence of βCD. The analysis of inclusion complex by DSC, FTIR, XRD, and SEM confirmed the formation of fisetin‐binary inclusion complex. Fisetin binary physical mixture and fisetin binary inclusion complex released 52.45% and 62.29% of drug, respectively. Higher drug released with inclusion complex could be due to formation of more water‐soluble inclusion complex. Fisetin binary inclusion complex exhibited significantly greater cytotoxicity on MCF‐7 cells than pure fisetin. A fisetin‐binary inclusion complex demonstrated a lower IC 50 value (71.36 µM) than pure fisetin (102.20 µM). A solvent‐evaporation‐derived fisetin‐binary inclusion complex was found to facilitate fisetin solubility and drug release. Further, enhanced cellular toxicity was observed in binary inclusion complex compared to pure drug. Hence, solvent evaporation approaches in conjunction with cyclodextrin features offer a promising way to overcome the solubility challenges associated with molecules like fisetin.