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.
Orienti
I
I
Department of Pharmaceutical Sciences, University of Bologna, Via S. Donato 19/2, 40127, Bologna, Italy. orienti@biocfarm.unibo.it
Cerchiara
T
T
Zecchi
V
V
Arias Blanco
M J
MJ
Gines
J M
JM
Moyano
J R
JR
Rabasco Alvarez
A M
AM
D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013816:Thermodynamics; D014580:Ursodeoxycholic Acid / Q000737:chemistry*; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D005079:Excipients; D047392:beta-Cyclodextrins; C403004:beta-cyclodextrin-choline dichloride; D014580:Ursodeoxycholic Acid