New clopidogrel napadisilate salt and its solid dispersion with improved stability and bioequivalence to the commercial clopidogrel bisulphate salt in beagle dogs

Title
New clopidogrel napadisilate salt and its solid dispersion with improved stability and bioequivalence to the commercial clopidogrel bisulphate salt in beagle dogs
Author(s)
용철순김용일[김용일]김경수[김경수]서귀현[서귀현]스리니바산 샤무감[스리니바산 샤무감]우종수[우종수]최한곤[최한곤]
Keywords
CARBOXYLIC-ACID METABOLITE; SPRAY-DRYING TECHNIQUE; IN-VIVO EVALUATION; PHYSICOCHEMICAL CHARACTERIZATION; GELATIN MICROCAPSULE; CRYSTALLINE CHANGE; MASS-SPECTROMETRY; HUMAN PLASMA; OPEN-LABEL; LC METHOD
Issue Date
201106
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.415, no.1-2, pp.129 - 139
Abstract
The purpose of this study was to develop a novel clopidogrel napadisilate-loaded solid dispersion with improved stability and bioequivalence to the clopidogrel bisulphate-loaded commercial product. Clopidogrel napadisilate prepared in this study appeared as a white crystalline powder unlike clopidogrel base. However, this salt did not improve the solubility of clopidogrel, even with improved stability compared to clopidogrel bisulphate. To improve the solubility of clopidogrel napadisilate, a novel clopidogrel napadisilate-loaded solid dispersion was prepared by the spray-drying technique using HPMC and colloidal silica, and the physicochemical properties, dissolution and bioavailability in beagle dogs were evaluated compared to the clopidogrel bisulphate-loaded commercial product. The solid dispersion composed of clopidogrel napadisilate, HPMC and colloidal silica at a weight ratio of 11.069/3/3.5 improved solubility by 6.5-fold compared to clopidogrel napadisilate, even if it did not improve drug solubility compared to clopidogrel bisulphate. However, unlike clopidogrel bisulphate, this formulation improved the stability of clopidogrel. Furthermore, the clopidogrel napadisilate solid dispersion-loaded tablet showed similar dissolution to the clopidogrel bisulphate-loaded commercial product and was bioequivalent to the commercial product in beagle dogs. Thus, this clopidogrel napadisilate-loaded solid dispersion could be a promising candidate for improving the stability and bioavailability of clopidogrel. (C) 2011 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/25092http://dx.doi.org/10.1016/j.ijpharm.2011.05.059
ISSN
0378-5173
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약학대학 > 약학부 > Articles
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