title: Novel solid self-emulsifying drug delivery system of coenzyme Q₁₀ with improved photochemical and pharmacokinetic behaviors.
abstract: The present study was undertaken to develop a solid self-emulsifying drug delivery system of coenzyme Q(10) (CoQ(10)/s-SEDDS) with high photostability and oral bioavailability. The CoQ(10)/s-SEDDS was prepared by spray-drying an emulsion preconcentrate containing CoQ(10), medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose, and its physicochemical, photochemical, and pharmacokinetic properties were evaluated. The CoQ(10)/s-SEDDS powder with a diameter of ca. 15 μm was obtained by spray-drying, in which the CoQ(10) was mostly amorphized. The CoQ(10)/s-SEDDS exhibited immediate self-emulsification when introduced to aqueous media under gentle agitation, forming uniform fine droplets with a mean diameter of ca. 280 nm. There was marked generation of reactive oxygen species, in particular superoxide, from CoQ(10) exposed to simulated sunlight (250W/m(2)), suggesting potent photoreactivity. Nano-emulsified solution of CoQ(10) under light exposure underwent photodegradation with 22-fold higher degradation kinetics than crystalline CoQ(10), although the CoQ(10)/s-SEDDS was less photoreactive. After the oral administration of CoQ(10)/s-SEDDS (100 mg-CoQ(10)/kg) in rats, enhanced exposure of CoQ(10) was observed with increases in both C(max) and AUC of ca. 5-fold in comparison with those of orally administered crystalline CoQ(10). From the improved physicochemical and pharmacokinetic data, the s-SEDDS approach upon spray-drying might be a suitable dosage option for enhancing nutraceutical and pharmaceutical values of CoQ(10).
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. onoue@u-shizuoka-ken.ac.jp
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
authors.forename: Atushi
authors.initials: A
authors.lastname: Uchida
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kuriyama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Seto
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Junya
authors.initials: J
authors.lastname: Hatanaka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D019587:Dietary Supplements / Q000528:radiation effects; D004337:Drug Carriers; D004355:Drug Stability; D004655:Emulsions; D005227:Fatty Acids / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008657:Metabolic Clearance Rate; D010316:Particle Size; D010782:Photolysis; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013481:Superoxides / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014280:Triglycerides / Q000737:chemistry; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000528:radiation effects
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005227:Fatty Acids; D008055:Lipids; D011208:Powders; D014280:Triglycerides; D013481:Superoxides; D014451:Ubiquinone; D002482:Cellulose; C008079:hydroxypropylcellulose; C024989:coenzyme Q10