title: Comparison of a solid SMEDDS and solid dispersion for enhanced stability and bioavailability of clopidogrel napadisilate.
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.
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Dong Wuk
authors.initials: DW
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Min Seok
authors.initials: MS
authors.lastname: Kwon
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Abid Mehmood
authors.initials: AM
authors.lastname: Yousaf
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Prabagar
authors.initials: P
authors.lastname: Balakrishnan
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Jong Hyuck
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Dong Shik
authors.initials: DS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Ajou University, 206, Worldcup-ro, Yeongtong-gu, Suwon 443-749, South Korea.
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Ajou University, 206, Worldcup-ro, Yeongtong-gu, Suwon 443-749, South Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Park
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea. Electronic address: jongohkim@yu.ac.kr.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea. Electronic address: hangon@hanyang.ac.kr.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000818:Animals; D000077144:Clopidogrel; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Bioavailability; Clopidogrel napadisilate; Solid SMEDDS; Solid dispersion; Stability