Bioavailability of theophylline and thiamine disulfide incorporated into mucoadhesive microspheres consisting of dextran derivatives and cellulose acetate butyrate.
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.
Miyazaki
Yasunori
Y
Pharmaceutical Department, Tokyo Women's Medical University Daini Hospital, Tokyo, Japan. myph@dnh.twkmu.ac.jp
Ogihara
Kanako
K
Yakou
Shigeru
S
Nagai
Tsuneji
T
Takayama
Kozo
K
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*
D003911:Dextrans; D004304:Dosage Forms; D012996:Solutions; D013535:Suspensions; D002482:Cellulose; C014396:cellulose acetate-butyrate; D013806:Theophylline; C013293:thiamine disulfide; D013831:Thiamine