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Clopidogrel Napadisilate Monohydrate Loaded Surface-Modified Solid Dispersion: Physicochemical Characterization and in Vivo Evaluation

Title
Clopidogrel Napadisilate Monohydrate Loaded Surface-Modified Solid Dispersion: Physicochemical Characterization and in Vivo Evaluation
Author
최한곤
Keywords
clopidogrel napadisilate monohydrate; surface-modified solid dispersion; water; stability; bioavailability; SIBUTRAMINE BASE; BEAGLE DOGS; BIOAVAILABILITY; SOLUBILITY; IBUPROFEN; STABILITY; DRUG; BIOEQUIVALENCE; ENHANCEMENT; DISSOLUTION
Issue Date
2015-07
Publisher
PHARMACEUTICAL SOC JAPAN
Citation
BIOLOGICAL & PHARMACEUTICAL BULLETIN, v. 38, No. 7, Page. 1033-1040
Abstract
To develop a novel solid dispersion of clopidogrel napadisilate monohydrate (CNM) with improved stability and oral bioavailability, surface-modified solid dispersions were prepared by spray-drying using water as a solvent, Tween 80 as a surfactant, and hydroxypropylmethyl cellulose (HPMC) as a hydrophilic polymer, and optimized according to drug solubility. Its solid-state characterization was evaluated by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The stability study was performed at 50 degrees C/75% RH over a period of 6 weeks. Its dissolution profiles and oral bioavailability in rats were also compared with that of CNM and clopidogrel bisulfate (CB). The solid dispersion, composed of CNM/HPMC/Tween80 at a weight ratio of 10/2.5/2.5, in which CNM was in the crystalline state, increased the drug solubility approximately 4.6-fold. It showed a significantly better dissolution profile than that of CNM in all the dissolution media, and gave either similar or higher dissolution compared to that of CB. This solubility and dissolution enhancement was attributed to improved wetting and solubilization of CNM crystals due to hydrophilic carriers attached on the drug surface. It had excellent stability, thereby addressing the stability problem of CB powder. Furthermore, it increased the area under curve (AUC) values by about 4-fold and 1.6-fold compared to CNM and CB, respectively, suggesting that it improved the oral bioavailability of the drug in rats. Thus, this solid dispersion system prepared with water, HPMC and Tween 80 can be used to enhance the bioavailability of CNM as well as to solve the stability problem of CB.
URI
https://www.jstage.jst.go.jp/article/bpb/38/7/38_b15-00113/_article/-char/ja/http://repository.hanyang.ac.kr/handle/20.500.11754/101290
ISSN
0918-6158
DOI
10.1248/bpb.b15-00113
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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