Abstract: AimTo study the pharmaceutical characterization, the pharmacokinetics and relative bioavailability of glimepiride gel-matrix controlled-release patch in rats. MethodsAn HPLC method was established for the determination of glimepiride in the permeation receptor and patch. The permeation rate and penetration mechanism of glimepiride-TDDS through rabbit skinin vitro was examined. The determination of drug content and the examination of weight difference and stability of the glimepiride-TDDS were carried out. Another HPLC method after pre-column derivatization was developed to determine the glimepiride serum concentration and then employed to study the pharmacokinetics and relative bioavailability of glimepiride after a single dose of oral or patch administration in rats. ResultsThe permeation tests through excised rabbit skin demonstrated that the optimized glimepiride controlled-release patch exhibited zero-order kinetic characteristics that satisfied the demands of original design. The determination of glimepiride content and the quality control of weight difference of the patch accorded with Pharmacopoeia of the People′s Republic of China of 2000 edition and the pharmaceutical characterization showed good stability. The HPLC method for the determination of serum glimepiride was shown to be a sensitive and simple one. The pharmacokinetic results showed that TDDS could decrease the maximum serum concentration, prolong the peak time, extend the MRT by 5.5 times compared with oral administration and maintain the serum concentration of glimepiride at a higher level even after 120 h of administration. The relative bioavailability of glimepiride-TDDS was 20.3% versus oral administration. ConclusionThe glimepiride-TDDS showed a slower, longer and smoother serum concentration-time profile, as compared with conventional oral administration in both absorption and elimination phase. As a result, it was evident that the patch exhibited good controlled-release properties.