title: In vitro dissolution and in vivo bioequivalence evaluation of two brands of isosorbide 5-mononitrate sustained release tablets.
abstract: The purpose of the present study was to test a sustained release-tablet newly formulated with synthetic paraffin and compare its bioequivalence to that of the Imdur® Long-Acting tablet, based on the guidelines of the Korean Food and Drug Administration.Dissolution test was performed in 4 different dissolution media. A LC/MS/MS method of isosorbide 5-mononitrate in human plasma was validated. In vivo bioequivalence tests of the 2 isosorbide 5-mononitrate tablets were performed in both preprandial and postprandial states.A comparative dissolution test gave similar results for both tablets in all dissolution media tested: 40% dissolution in pH 1.2 at 2 h and 80% dissolution in pH 4.0, pH 6.8, or water at 10 h. In a bioequivalence study to compare 2 tablets, the mean total area under the curve (AUCt) and peak concentration (Cmax) in the fasted state were 8 476.0 ng · h/mL and 540.4 ng/mL, respectively, for the Imdur® Long Acting Tablet 60 mg, and 8 701.4 ng · h/mL and 564.2 ng/mL, respectively, for the test tablet. The mean AUCt and Cmax in the fed state were 8 793.5 ng · h/mL and 559.9 ng/mL, respectively, for the Imdur® Long-Acting tablet 60 mg, and 8 639.8 ng · h/mL and 617.9 ng/mL, respectively, for the test tablet. The 90% confidence intervals using log transformed data were within the acceptable range of 0.8 - 1.25.Based on these statistical analyses, we conclude that the test tablet is bioequivalent to the Imdur® Long-Acting tablet 60 mg in both the preprandial and postprandial states.
authors.affiliation: Kolon Pharmaceuticals Inc., Korea.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Kim
authors.forename: K-S
authors.initials: KS
authors.lastname: Choi
authors.forename: S-H
authors.initials: SH
authors.lastname: Kam
authors.forename: K-H
authors.initials: KH
authors.lastname: Lee
authors.forename: J-S
authors.initials: JS
authors.lastname: Park
mesh_terms: D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D006801:Humans; D007202:Indicators and Reagents; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D019518:Postprandial Period; D015203:Reproducibility of Results; D012995:Solubility; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D014665:Vasodilator Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D007202:Indicators and Reagents; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate