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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.

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Bioavailability of Theophylline and Thiamine Disulfide Incorporated into Mucoadhesive Microspheres Consisting of Dextran Derivatives and Cellulose Acetate Butyrate