Inclusion complexes of trihexyphenidyl with natural and modified cyclodextrins

Abstract

Abstract The solubility of trihexyphenidyl (Thp) was improved by its combination with β-cyclodextrin (β−CD) and modified β-CDs. The solubility of Thp was found to be increased in the presence of β-CD, hydroxypropyl-β-cyclodextrin (HP-β-CD), methyl-β-cyclodextrin (Me-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD). In particular, the solubility of Thp in conjunction with SBE-β-CD was increased by a factor of 11. The formation constant (K c ) for the Thp/SBE-β-CD inclusion complex was determined to be 2300 L/mol based on fluorometry data. The structure of the Thp/SBE-β-CD complex in aqueous solution was examined by 1H-1H rotating frame nuclear Overhauser effect spectroscopy (ROESY) NMR, and the phenyl moiety of the Thp was found to coordinate with the secondary hydroxyl face of the SBE-β-CD. A solid Thp/SBE-β-CD inclusion complex was prepared by freeze-drying.