title: Preparation and evaluation of double-phased mucoadhesive suppositories of lidocaine utilizing Carbopol and white beeswax.
abstract: In an attempt to restrict drug absorption from suppositories to only the lower rectum, mucoadhesive lidocaine (LID) suppositories were prepared using Witepsol H-15 as a base, and Carbopol 934P (CP) and white beeswax (WAX) as additives. CP has a mucoadhesive property and WAX gives the suppositories stiffness. The suppositories containing 10% CP and 20% WAX stayed in the lower recta of rats for at least 2 h. Double-phased suppositories consisting of a front layer containing 10% CP and 20% WAX and a terminal layer containing LID and various amounts of CP were prepared. In vitro release profiles of LID from double-phased suppositories were similar to conventional single-phased suppositories containing CP alone. Values of AUC(0-6 h) and MRT of LID after administration of double-phased suppositories to rabbits were larger than those for single-phased suppositories with or without CP. On the other hand, the initial plasma metabolites concentrations after administration of double-phased suppositories were significantly lower and tended to exhibit delayed T(max) compared to single-phased suppositories. These results suggest that the double-phased mucoadhesive suppositories suppress initial metabolism of LID, and may be useful for improving bioavailabilities of drugs, like LID, which accept first-pass effect considerably.
authors.affiliation: Department of Clinical Pharmacy, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Yahagi
authors.forename: H
authors.initials: H
authors.lastname: Onishi
authors.forename: Y
authors.initials: Y
authors.lastname: Machida
mesh_terms: D000180:Acrylic Resins; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D008012:Lidocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D011145:Polyvinyls / Q000008:administration & dosage*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013488:Suppositories; D014885:Waxes
chemical_list: D000180:Acrylic Resins; D000779:Anesthetics, Local; D011145:Polyvinyls; D013488:Suppositories; D014885:Waxes; C006912:carboxypolymethylene; C038228:beeswax; D008012:Lidocaine