The Influence of Cosolvent on the Complexation of HP-β-cyclodextrins with Oleanolic Acid and Ursolic Acid

Abstract

Abstract. The present work was aimed at the influence of ethanol on the complex formation of hydroxypropyl-β-cyclodextrin (HP-β-CD) with oleanolic acid (OA) and ursolic acid (UA), two insoluble isomeric triterpenic acids. Phase solubility studies were carried out to evaluate the solubilizing power of HP-β-CD, in association with ethanol, toward OA and UA. A mathematical model was applied to explain and predict the solubility of OA and UA influenced by HP-β-CD and ethanol. The solid complexes were prepared by evaporating the filtrate of samples which was prepared in different complexing media. The solubility of OA is much higher than that of UA in all the tested aqueous solutions. The solubility of OA and UA can be increased over 900 and 200 times, respectively, by forming complex with HP-β-CD. Ethanol (0.5%, v/v) can help the formation of OA-HP-β-CD complex, but is harmful to the formation of UA-HP-β-CD complex. Increasing solubility in water can be achieved by adding ethanol into the complexing media, but the concentration of ethanol should be optimized. The ring E of the chemical compounds has a great influence on the complexing process.

Design and development of dry powder sulfobutylether-β-cyclodextrin complex for pulmonary delivery of fisetin

“…The ethanol content affected the stability of the formed complexes, with sub-optimal compositions resulting in precipitation of fisetin within 3 h of preparation. It has been reported ethanol content should be optimized, as too high solvent content reduces the inclusion of drug, as solvent will competitively bind to the cyclodextrin molecules [26]. In this study, this may cause the expulsion of fisetin from the cavity of cyclodextrin, causing precipitation.…”

Effect of Cyclodextrin Types and Co-Solvent on Solubility of a Poorly Water Soluble Drug

“…The combined method of CDs complexation and the use of a co-solvent is an approach of interest which has been reported by a number of studies [12,13,14,15,16]. In theory, only the molecular structure of the guest molecule is responsible for the inclusion complex formation with CDs; the presence of a co-solvent, thus, helps by facilitating the complex formation by dissolving the guest before entering the cavity.…”

Solid dispersions containing ursolic acid in Poloxamer 407 and PEG 6000: A comparative study of fusion and solvent methods

“…Regarding the latter alternative, ursolic acid has been formulated with liposomes, hydroxypropyl β cyclodextrin and nanostructured lipid carriers [18][19][20]. However, none of these approaches demonstrated significant ursolic acid solubility enhancement.…”