Development of Fisetin Formulation for Improved Solubility and Dissolution Rate

Recently, the anti-aging and anti-inflammatory therapeutic effects of fisetin, a natural flavonoid, have been gaining attention. It is classified as a Class II drug under the Biopharmaceutical Classification System [BCS], is poorly soluble, and exhibits a pH-dependent solubility pattern. The purpose of this study is to increase the solubility and dissolution rate of fisetin (FST) and to ensure the stabilization of solid-dispersion (SD). The strategy is to adsorb fisetin onto Aerosil300® and optimize it through polymer screening. The FST-SD was developed using the solvent evaporation method with ethyl alcohol. The optimal formulation (HB-SD1) was FST : Aerosil300® : K12®=1 : 3 : 5 (w/w), and the dissolution rates were 76.4±2.8% (pH 1.2), 73.9±1.8% (pH 4.0), and 80.6±1.8% (pH 6.8), showing results 5.2-, 5.4-, and 4.4-fold higher than FST pure, respectively. Changes in the physicochemical properties of the HB-SD1 formulation were observed, and the pre-dissolution rate of the solvent evaporation method was the highest even with different manufacturing methods. In vitro drug release evaluation, the drug release rate of the HB-SD1 formulation was 3.0-fold (FST pure) and 2.3-fold (HB-PM1) higher. In addition, the HB-SD1 formulation demonstrated stability for three months. In conclusion, we succeeded in solubilizing and stabilizing the flavonoid drug as fisetin. Overall, the findings of this study may serve as a basis for future investigations of anti-inflammatory effects at the cellular level and oral bioavailability in rats.