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 Q 10 (CoQ 10 ) using a newly developed cold wet-milling (CWM) system to enhance the dissolution and biopharmaceutical properties of CoQ 10 . CSD formulations of CoQ 10 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 CoQ 10 led to successful development of a CSD formulation (CoQ 10 /CWM) with a mean CoQ 10 diameter of ca. 129 nm, although a conventional wet-milling system failed due to evident formation of large particles. In comparison with crystalline CoQ 10 , marked improvement in the aqueous dissolution was seen for the CoQ 10 /CWM, with no significant decrease of photostability. Oral bioavailability and hepatoprotective effects of orally dosed CoQ 10 samples were also evaluated in rats. After oral administration of CoQ 10 /CWM (100 mg CoQ 10 /kg) in rats, there appeared to be a similar T max value and 13-fold increase of bioavailability compared with crystalline CoQ 10 . In a rat model of acute liver injury, pretreatment with CoQ 10 /CWM (100 mg CoQ 10 /kg, twice) led to marked attenuation of hepatic damage as evidenced by decreased ALT and AST, surrogate biomarkers for hepatic injury, whereas crystalline CoQ 10 was less effective. The CSD approach with the new CWM system might be a promising dosage option for improving the nutraceutical values of CoQ 10 .