title: Effect of glycyrrhizinate on dissolution behavior and rectal absorption of amphotericin B in rabbits.
abstract: The effects of dipotassium glycyrrhizinate (GLYK) on the dissolution behavior and bioavailability of amphotericin B (AMB) were investigated. The mixtures of AMB and GLYK were prepared at different molar ratios by lyophilization. Lyophilization resulted in amorphous AMB either alone or in the mixture. Dissolution rates of AMB of the mixtures were markedly faster than that of lyophilized AMB alone, which was followed by a decrease of dissolution. The initially-enhanced dissolution rate was likely to be due to the improvement of surface wettability of drug particles with GLYK rather than the amorphous state of AMB. A phase solubility study of AMB with GLYK indicated that the increasing solubility was caused by micellar solubilization. The in vitro release rate of AMB from suppositories containing the lyophilized mixtures was significantly accelerated by increasing the amount of GLYK. The rectal absorption of AMB from suppositories containing either the drug alone, a physical mixture or a lyophilized mixture was studied using rabbits. The absorption of the mixture (AMB/GLYK = 1/9) was about 35 times greater in the area under the serum concentration-time curve (0-24 h) than that of lyophilized AMB alone. These results suggest that GLYK is useful for improving the dissolution property of AMB and the bioavailability of the drug incorporated in suppositories.
authors.affiliation: Research Laboratories, Bristol-Myers Squibb K. K., Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: E
authors.initials: E
authors.lastname: Kuwahara
authors.forename: O
authors.initials: O
authors.lastname: Koyama
authors.forename: K
authors.initials: K
authors.lastname: Ohkubo
authors.forename: T
authors.initials: T
authors.lastname: Yotsuyanagi
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D011817:Rabbits; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D013488:Suppositories
chemical_list: D013488:Suppositories; D019695:Glycyrrhizic Acid; D000666:Amphotericin B; D006034:Glycyrrhetinic Acid