Inclusion complexes of trihexyphenidyl with natural and modified cyclodextrins

The solubility of trihexyphenidyl (Thp) was improved by its combination with beta-cyclodextrin (beta-CD) and modified beta-CDs. The solubility of Thp was found to be increased in the presence of beta-CD, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), methyl-beta-cyclodextrin (Me-beta-CD) and sulfobutylether-beta-cyclodextrin (SBE-beta-CD). In particular, the solubility of Thp in conjunction with SBE-beta-CD was increased by a factor of 11. The formation constant (K-c) for the Thp/SBE-beta-CD inclusion complex was determined to be 2300 L/mol based on fluorometry data. The structure of the Thp/SBE-beta-CD complex in aqueous solution was examined by H-1-H-1 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-beta-CD. A solid Thp/SBE-beta-CD inclusion complex was prepared by freeze-drying.