Complexation of ursodeoxycholic acid with beta-cyclodextrin-choline dichloride coprecipitate.

The inclusion complexes of ursodeoxycholic acid (UDCA) with beta-cyclodextrin (betaCD) coprecipitated with choline dichloride (CDC) or beta-cyclodextrin were investigated to evaluate the effect of the presence of choline for UDCA inclusion in betaCD. The inclusion complexes were investigated in solution by phase solubility diagrams and 1H NMR spectrometry and in solid state (kneading, freeze-drying, sealed heating and spray-drying) by DSC, SEM, HSM, XRD and IR spectroscopy. Stability constants were determined at pH 5.5 and 7.0 to simulate the environmental pH of the first intestinal tract and at different temperatures (25, 30 and 37 degrees C) to obtain the thermodynamic parameters of inclusion. Both betaCD-CDC and betaCD increased the water solubility of UDCA particularly betaCD-CDC. All complexes showed a high dissolution rate particularly the spray-dried complexes obtained in the presence of betaCD-CDC.

Nuclear magnetic resonance investigations of the inclusion complexation of gliclazide with beta-cyclodextrin.

The formation of the gliclazide-beta-cyclodextrin (GL-beta-CD) inclusion compound has been studied in the liquid state by phase solubility techniques and by 1H and 13C NMR spectroscopy. From the initial straight portion of the solubility curve (Bs type), the value of the apparent stability constant (Kc) was calculated as 1094 M(-1). The nuclear magnetic resonance studies confirm that GL yields a complex with beta-CD in aqueous medium, which is mainly due to the penetration of the azabicyclooctyl group of GL into the cavity of beta-CD. The study of the monodimensional nuclear Overhauser effect (NOE) of the H3 proton of CD has shown that the tolyl group also interacts with CD, but to a lesser extent than the azabicyclooctyl moiety. Finally, the application of the continous variation technique confirmed the 1:2 drug:CD stoichiometry of the complex.