title: Bioavailability of theophylline and thiamine disulfide incorporated into mucoadhesive microspheres consisting of dextran derivatives and cellulose acetate butyrate.
abstract: Mucoadhesive microspheres made of oppositely charged dextran derivatives and cellulose acetate butyrate (Ad-MS) were evaluated for their ability to improve the bioavailability of theophylline (TH) and thiamine disulfide (TDS). A drug suspension (or solution) and non-adhesive microspheres (MS) were used as references. In vitro drug release profiles from MS and Ad-MS were similar for each drug, whereas their gastrointestinal transits differed. The plasma concentration after oral administration of drug suspension (or solution), MS and Ad-MS was investigated in rats. In the case of TH, sustained plasma level profiles were observed after MS or Ad-MS administration, with similar C(max), T(max) and MRT( infinity ) values. AUC( infinity ) values of the suspension, MS and Ad-MS were statistically equivalence. These indicated that Ad-MS achieved a sustained plasma level profile without a decrease of AUC. In the case of TDS, MRT( infinity ) and AUC( infinity ) of Ad-MS were significantly larger than those of the solution and MS, indicating that the plasma level was sustained and the extent of bioavailability was increased. These results suggested that Ad-MS is a promising device for improvement of bioavailability of drugs those absorption windows are limited to upper part of the gastrointestinal tract.
authors.affiliation: Pharmaceutical Department, Tokyo Women's Medical University Daini Hospital, Tokyo, Japan. myph@dnh.twkmu.ac.jp
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Kanako
authors.initials: K
authors.lastname: Ogihara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yakou
authors.forename: Tsuneji
authors.initials: T
authors.lastname: Nagai
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism; D004304:Dosage Forms; D007408:Intestinal Absorption / Q000187:drug effects; D008863:Microspheres; D051381:Rats; D012996:Solutions; D013535:Suspensions; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013831:Thiamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D003911:Dextrans; D004304:Dosage Forms; D012996:Solutions; D013535:Suspensions; D002482:Cellulose; C014396:cellulose acetate-butyrate; D013806:Theophylline; C013293:thiamine disulfide; D013831:Thiamine