title: Development of novel cilostazol-loaded solid SNEDDS using a SPG membrane emulsification technique: Physicochemical characterization and in vivo evaluation.
abstract: The objective of this study was to develop a novel solid self-nanoemulsifying drug delivery system (SNEDDS) using a membrane emulsification technique involving Shirasu porous glass (SPG) which produced very small and uniform emulsion droplets, resulting in enhanced solubility, dissolution and oral bioavailability of poorly water-soluble cilostazol. The effects of carriers on the drug solubility were assessed, and pseudo-ternary phase diagrams were plotted. Among the liquid SNEDDS formulations tested, the liquid SNEDDS composed of peceol (oil), Tween 20 (surfactant) and Labrasol (cosurfactant) at a weight ratio of 15/55/30, produced the smallest emulsion droplet size. The cilostazol-loaded liquid SNEDDS formulation was suspended in the distilled water and subjected to SPG membrane emulsification. Calcium silicate was added as a solid carrier in this liquid SNEDDS, completely suspended and spray-dried, leading to the production of a cilostazol-loaded solid SNEDDS. The emulsion droplet size, solubility and dissolution of the emulsified solid SNEDDS were assessed as compared to the solid SNEDDS prepared without emulsification. Moreover, the physicochemical characteristics and pharmacokinetics in rats were evaluated with the emulsified solid SNEDDS. The emulsified solid SNEDDS provided significantly smaller and more uniform nanoemulsions than did the non-emulsified solid SNEDDS. The emulsified solid SNEDDS showed significantly higher drug solubility and dissolution as compared to the non-emulsified solid SNEDDS. The crystalline drug in it was converted into the amorphous state. Moreover, in rats, it gave significantly higher initial plasma concentrations and AUC compared to the drug powder, suggesting its improved oral bioavailability of cilostazol. Thus, this novel solid SNEDDS developed using a membrane emulsification technique represents a potentially powerful oral delivery system for cilostazol.
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea; International Center of Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Omer
authors.initials: O
authors.lastname: Mustapha
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: Kyung Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Dow University of Health Sciences, Karachi, Sindh, Pakistan.
authors.forename: Shumaila
authors.initials: S
authors.lastname: Shafique
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 & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
authors.forename: Sung Giu
authors.initials: SG
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.
authors.forename: Youn Gee
authors.initials: YG
authors.lastname: Seo
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, 440-746, South Korea.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong Dongjak-gu, Seoul, 156-756, South Korea.
authors.forename: Kyung Taek
authors.initials: KT
authors.lastname: Oh
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: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D000077407:Cilostazol; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D005898:Glass; D005989:Glycerides / Q000737:chemistry; D008297:Male; D008567:Membranes, Artificial; D049329:Nanostructures; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013696:Temperature; D013777:Tetrazoles / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D008567:Membranes, Artificial; D011136:Polysorbates; D013777:Tetrazoles; C440220:Labrasol; D014867:Water; D000077407:Cilostazol
keywords: Bioavailability; Cilostazol; Emulsion droplet size; Membrane emulsification; Shirasu porous glass membrane; Solid self-nanoemulsifying drug delivery system; Solubility