title: Biopharmaceutical characterization of nanocrystalline solid dispersion of coenzyme Q10 prepared with cold wet-milling system.
abstract: The present study aimed to develop a nano-crystalline solid dispersion (CSD) of coenzyme Q10 (CoQ10) using a newly developed cold wet-milling (CWM) system to enhance the dissolution and biopharmaceutical properties of CoQ10. CSD formulations of CoQ10 were prepared by the CWM system, and their physicochemical properties were characterized in terms of morphology, crystallinity, particle size distribution, dissolution, and photostability. Application of the CWM system to CoQ10 led to successful development of a CSD formulation (CoQ10/CWM) with a mean CoQ10 diameter of ca. 129 nm, although a conventional wet-milling system failed due to evident formation of large particles. In comparison with crystalline CoQ10, marked improvement in the aqueous dissolution was seen for the CoQ10/CWM, with no significant decrease of photostability. Oral bioavailability and hepatoprotective effects of orally dosed CoQ10 samples were also evaluated in rats. After oral administration of CoQ10/CWM (100 mg CoQ10/kg) in rats, there appeared to be a similar Tmax value and 13-fold increase of bioavailability compared with crystalline CoQ10. In a rat model of acute liver injury, pretreatment with CoQ10/CWM (100 mg CoQ10/kg, twice) led to marked attenuation of hepatic damage as evidenced by decreased ALT and AST, surrogate biomarkers for hepatic injury, whereas crystalline CoQ10 was less effective. The CSD approach with the new CWM system might be a promising dosage option for improving the nutraceutical values of CoQ10.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: onoue@u-shizuoka-ken.ac.jp.
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Terasawa
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Yuminoki
authors.affiliation: Department of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D008027:Light; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D020011:Protective Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D020011:Protective Agents; D014451:Ubiquinone; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C024989:coenzyme Q10
keywords: Bioavailability; Coenzyme Q(10); Dissolution; Hepatoprotection