Examination of intermolecular interaction as a result of cogrinding actarit and β-cyclodextrin

In this study, investigations were performed in regard to the possibility of complexation of actarit (ACT) with beta-cyclodextrin (beta-CD) for improving the solubility and dissolution rate. Complexes of beta-CD and ACT (ACT/beta-CD molar ratio = 1/1) were prepared using the cogrinding method. Formation of an ACT/beta-CD inclusion complex by cogrinding was confirmed using powder X-ray diffraction measurement. The powder X-ray diffraction of the ground mixture (ACT/beta-CD = 1/1) showed a halo pattern. The diffraction pattern of the ground mixture after storage at RH 82 %, 40 degrees C exhibited new diffraction peaks at 2h = 11.6 degrees and 17.8 degrees, and differed from those of ACT and beta-CD crystals. In vitro studies showed that the solubility and dissolution rate of ACT were significantly improved by complexation with beta-CD with respect to the drug alone. In H-1-NMR measurement, changes in chemical shift (1H) suggested that the drug phenyl moiety was included in the cavities of beta-CD mainly by hydrophobic interaction, and that the primary hydroxy side of beta-CD was tightly associated with each drug. The results show clear evidence of intermolecular interaction between beta-CD and ACT.