Abstract
The dissolution kinetics of the cotnn~on crystal- line forms of cholesterol (anhydrate and monohydrate) were studied in free and conjugated chenodeoxycholate and ursodeoxycholate solutions by static disk, rotating disk, and powder dissolution techniques. 'The dissolution kinetics of both forms of cholesterol were found to be non-diffusion controlled, i.e., the detachment rate of cholesterol molecules from the solid crystals was rate-limiting. Cholesterol dis- solution rates in chenodeoxycholate solutions were sig- nificantly faster than in ursodeoxycholate solutions, and micellar solubilities and dissolution rates of anhydrous cholesterol were appreciably larger than those of cholesterol monohydrate. In free and conjugated chenodeoxycholate solutions, the higher solubilities of anhydrous cholesterol converged to the lower solubilities of the monohydrate within a few days, but in ursodeoxycholate solutions anhy- drous cholesterol remained metastable fol- weeks. taurine conjugates). 1)issolution rates were also increased by increases in tcrnperature (17-47C), but no change was observed at the polymorphic crystalline transition temperature of anhyclrous cholesterol (39°C). Linear extrapolations of the temperature dependence of' the dissolution rate constants for both f'ornls of cholesterol converged at higher temperatures ;ind intersected at 86.7C. This temperature has been shown by other methods to he the transition temperature wherc cholesterol nlono- hydrate is convertcd to the anh>drous form. Dissolution rates were retarded markedly by prtial protonation of the bile salt suggesting that sparingly soluble bile acids and cholesterol rnay cornpete for micellar hinding sites.ml'hese studies suggest that nlicellar dissolution rates of cholestcrol gallstones during therapy with ursodeoxycholic acid should be appreciably slowet- than during therapy with cheno- deoxycholic acid. Since he clinical efficacy of gallstone dis- solution with either agent appears to be similar, it is coli- clutled that ~,hysical-chemical nwchanisms other than micellar solubilization may be operative in ursodeoxy- cholate-induced gallstone dissolution.-Igimi,
Highlights
) were studied in freeandconjugatedchenodeoxycholate and ursodeoxycholate solutions by static disk, rotating disk, and powderdissolution techniques
Cholesterol(Nu-ChekPrep,Austin,MN) was recrystallizedthricefromhot 95% EtOHandmixed with [ I, 2-'H]cholesterol ( N e w England Nuclear Co., Boston, MA) to provide, as required=, 5 gram batches temperature( 4 3 ° cholesterol solubilities (Cs) )a n dt h e ns eeded with a f-ew crystals of pure cholesterol monohydrate (ChM) ( 1 1)
Influence of cholesterol disk-pressure on dissolution rates surface into solution under these conditions
Summary
) were studied in freeandconjugatedchenodeoxycholate and ursodeoxycholate solutions by static disk, rotating disk, and powderdissolution techniques. Dissolution rates were retarded markedly by prtial protonation o f the bile salt suggesting that sparingly soluble bile acids and cholesterol rnay cornpete for micellar hinding sites.ml'hese studies suggest that nlicellar dissolution rates of cholestcrol gallstones during therapy with ursodeoxycholic acid should be appreciably slowet- thanduringtherapy with chenodeoxycholic acid. Since he clinical efficacy o f gallstone dissolution w i t h either agent appears to be similar, it is coliclutled that ~,hysical-chemicanlwchanisms othetrhan micellar solubilization may be operative in ursodeoxycholate-induced gallstondeissolution.-Igimi, H., and. Cholesteryl esters may form liquid crystalline accumulations in the liver, gallbladder wall, and reticulo-endothelial systems (4)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
