The synthesis, crystal properties, cyclodextrin complexation and photochemical stability of selected curcuminoids

Abstract

ABSTRACT

R1 R2 Mw RHC-1 -OCH3 -OCH3 396.42 RHC-2 -OCH3 -OH 368.37 RHC-3 -H -OH 308.32 RHC-4 -H -OCH3 336.39 RHC-5 -OH -OH 340.32

A selection of curcuminoids has been synthesized and complexed to HPβCD, MβCD and HPγCD. The influence of concentration of cyclodextrin (CD), of ionic strength, choice of buffer salt and pH on aqueous phase solubility was investigated. In addition it was investigated if the use Mg2+ together with the CDs could increase the aqueous solubility of curcuminoids. Melting point and polymorphic forms of the curcuminoids were investigated using differential scanning calorimetry (DSC), and photochemical stability was investigated in hydrogen bonding organic solvent, EtOH, a mixture of this organic solvent and water and in aqueous solution of 10% HPβCD and HPγCD. The ionic strength or addition of Mg2+ did not influence the solubility, nor did pH when kept at pH 5 or lower. The stoichiometry of the curcuminoids-CD complexes was not unequivocally determined, but some sort of higher-order complex or non-inclusion complexation seems to be present. Solubility was found to be best for curcumin in HPγCD and best for bisdemethoxycurcumin in the βCDs. Different batches of the curcuminoids have formed different crystal forms, with slightly different melting points. This is assumed to have an effect on the aqueous solubility. Photochemical stability was found to be generally better for curcumin than for the other curcuminoids, presumably due to intramolecular bondings. The stability was best in hydrogen bonding organic solvent for all the curcuminoids. An attempt was made to synthesize a curcumin galactoside, with postulated increased aqueous solubility. This was not successful.