Stoichiometry-dependent changes of solubility and photoreactivity of an antiulcer agent, 2′-carboxymethoxy-4,4′-bis(3-methyl-2-butenyloxy) chalcone, in cyclodextrin inclusion complexes

Abstract An antiulcer agent, 2′-carboxymethoxy-4,4′-bis(3-methyl-2-butenyloxy) chalcone (CBC), formed inclusion complexes with α-, β- and γ-cyclodextrins (α-, β- and γ-CyDs) in molar ratios (guest:host) of 1:1 and 1:2 in water. The low aqueous solubility of CBC (1.1 × 10 −5 M) was significantly improved by CyD complexations, the degree of the enhancing effect differing depending on the stoichiometry of the complexes. The α- and β-CyD complexes with a stoichiometry of 1:2 have higher solubilities in water than the corresponding 1:1 complexes, whereas the solubility of the 1:2 γ-CyD complex was lower than that of the 1:1 complex because of the complete inclusion of CBC in a γ-CyD dimer which is less hydrated. The 1:1 and 1:2 complexes showed different photoreactivities, i.e., the ( E )-( Z ) photoisomerization of CBC was decelerated in the 1:1 complex due to the steric effect, while rather accelerated in the 1:2 complex due to the microsolvent effect. The β- and γ-CyD solid complexes of CBC with a 1:2 stoichiometry were prepared on the basis of the phase solubility diagram, and their dissolution behaviors were investigated. The dissolution rate of the β-CyD complex was much faster than that of the γ-CyD complex, probably due to the lower solubility and wettability of the 1:2 γ-CyD complex. The present data indicated that physicochemical properties, such as solubility and reactivity, of CyD complexes are changed depending on the stoichiometry, and thus CyD concentrations should be optimized for a rational design of CBC formulation.