Water Solubility and Dissolution Enhancement of Fisetin by Spherical Amorphous Solid Dispersion in Polymer of Cyclodextrin

Abstract

Fisetin (3, 7, 3', 4'-tetrahydroxyflavone) is an active ingredient characterized by a large spectrum of biological activities with a wide range of nutraceutical properties, including neuroprotecting, antidiabetic and suppression or prevention of tumors. The only drawback limiting its use is its low water solubility. The present work was focused on the solubility improvement of fisetin using spray-drying solid dispersion method, using also cyclodextrin polymers and which is extensively employed as technique to enhance poorly-water soluble compounds. Fisetin solubility was evaluated in the presence of poly-aβ-CD, poly-aγ-CD, poly-aβγ-CD and poly-methyl-β-CD by Higuchi solubility study. Spherical Amorphous solid dispersion formulations were prepared using polymethyl- β-CD (choice of the polymer was based on the better results of solubility study) at different ratios drug: polymer (1:1) and (1:3). In addition, different formulations were investigated using several techniques such as: Fourier Transformed Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), NMR and Scanning Electron Microscopy (SEM). The in vitro dissolution was performed in water at 37°C. The results of dissolution studies showed a complete dissolution observed with the formulation ratio 1:3 while the formulation ratio 1:1 showed a maximum dissolution rate about 59%. This difference is due to the formation of watersoluble inclusion complex and on the other hand to the high hydrophilicity of the cyclodextrin polymer.