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Arzneimittelforschung 2012; 62(12): 576-582
DOI: 10.1055/s-0032-1327614
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

In vitro Dissolution and in vivo Bioequivalence Evaluation of Two Brands of Isosorbide 5-mononitrate Sustained Release Tablets

Y.-H. Kim
2   Kolon Pharmaceuticals Inc., Korea
2   Kolon Pharmaceuticals Inc., Korea
,
K.-S. Choi
2   Kolon Pharmaceuticals Inc., Korea
,
S.-H. Kam
2   Kolon Pharmaceuticals Inc., Korea
,
K.-H. Lee
2   Kolon Pharmaceuticals Inc., Korea
,
J.-S. Park
1   College of Pharmacy, Chungnam National University, Korea
› Author Affiliations
Further Information

Publication History

received 24 August 2012

accepted 17 September 2012

Publication Date:
23 October 2012 (online)

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Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

Key words

sustained release - isosorbide 5-mononitrate - in vitro dissolution - bioequivalence
 

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