Comparison of a solid SMEDDS and solid dispersion for enhanced stability and bioavailability of clopidogrel napadisilate

Title
Comparison of a solid SMEDDS and solid dispersion for enhanced stability and bioavailability of clopidogrel napadisilate
Author(s)
김종오김동욱[김동욱]권민석[권민석]아비드유사프[아비드유사프]프라바가[프라바가]박종혁[박종혁]김동식[김동식]이범진[이범진]박영준[박영준]최한곤[최한곤]용철순
Keywords
SPRAY-DRYING TECHNIQUE; DRUG-DELIVERY SYSTEMS; CARBOXYLIC-ACID METABOLITE; PHYSICOCHEMICAL CHARACTERIZATION; BEAGLE DOGS; SIBUTRAMINE BASE; DOSAGE FORM; FORMULATION; FLURBIPROFEN; VOLUNTEERS
Issue Date
201412
Publisher
ELSEVIER SCI LTD
Citation
CARBOHYDRATE POLYMERS, v.114, pp.365 - 374
Abstract
The intention of this study was to compare the physicochemical properties, stability and bioavailability of a clopidogrel napadisilate (CN)-loaded solid dispersion (SD) and solid self-microemulsifying drug delivery system (solid SMEDDS). SD was prepared by a surface attached method using different ratios of Cremophor RH60 (surfactant) and HPMC (polymer), optimized based on their drug solubility. Liquid SMEDDS was composed of oil (peceol), a surfactant (Cremophor RH60) and a co-surfactant (Transcutol HP). A pseudo-ternary phase diagram was constructed to identify the emulsifying domain, and the optimized liquid SMEDDS was spray dried with an inert solid carrier (silicon dioxide), producing the solid SMEDDS. The physicochemical properties, solubility, dissolution, stability and pharmacokinetics were assessed and compared to clopidogrel napadisilate (CN) and bisulfate (CB) powders. In solid SMEDDS, liquid SMEDDS was absorbed or coated inside the pores of silicon dioxide. In SD, hydrophilic polymer and surfactants were adhered onto drug surface. The drug was in crystalline and molecularly dispersed form in SD and solid SMEDDS, respectively. Solid SMEDDS and SD greatly increased the solubility of CN but gave lower drug solubility compared to CB powder. These preparations significantly improved the dissolution of CN, but the latter more increased than the former. Stability under accelerated condition showed that they were more stable compared to CB powder, and SD was more stable than solid SMEDDS. They significantly increased the oral bioavailability of CN powder. Furthermore, SD showed significantly improved oral bioavailability compared to solid SMEDDS and CB powder. Thus, SD with excellent stability and bioavailability is recommended as an alternative for the clopidogrel-based oral formulation. (C) 2014 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/30341http://dx.doi.org/10.1016/j.carbpol.2014.08.034
ISSN
0144-8617
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약학대학 > 약학부 > Articles
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