Comparison of a solid SMEDDS and solid dispersion for enhanced stability and bioavailability of clopidogrel napadisilate
- Authors
- Kim, Dong Wuk; Kwon, Min Seok; Yousaf, Abid Mehmood; Balakrishnan, Prabagar; Park, Jong Hyuck; Kim, Dong Shik; Lee, Beom-Jin; Park, Young Joon; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon
- Issue Date
- Dec-2014
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Clopidogrel napadisilate; Solid dispersion; Solid SMEDDS; Stability; Bioavailability
- Citation
- CARBOHYDRATE POLYMERS, v.114, pp.365 - 374
- Indexed
- SCIE
SCOPUS
- Journal Title
- CARBOHYDRATE POLYMERS
- Volume
- 114
- Start Page
- 365
- End Page
- 374
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/21044
- DOI
- 10.1016/j.carbpol.2014.08.034
- ISSN
- 0144-8617
- 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.
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