Research and Publications
>> Assessment of coenzyme Q10 absorption using an in vitro digestion-Caco-2 cell model
The feasibility of using a coupled in vitro digestion-Caco-2 cell uptake as a model for examining the digestive stability and absorption of coenzyme Q10 (CoQ10) from a variety of commercially available CoQ10 products was examined. The products were first subjected to simulated digestion to mimic their passage through the GI tract to generate micelles containing CoQ10, and the micelle fractions added to monolayers of Caco-2 cells to determine CoQ10 uptake. The data demonstrate enhanced uptake of CoQ10 from formulations containing solubilized forms of CoQ10 and also from a CoQ10–-cyclodextrin complex as compared with pure CoQ10 powder or tablets based on CoQ10 powder. The CoQ10 uptake by the cells was correlated with the extent of micellarization of CoQ10 during simulated digestion. Most of CoQ10 taken up by the cells was converted to ubiquinol either during or following uptake. The data also indicate a correlation between in vitro dissolution of CoQ10 products and uptake of CoQ10 by Caco-2 cells. Thus, this study demonstrates the utility of coupled in vitro digestion-Caco-2 cell model as a cost-effective screening tool that will provide useful information for the optimal design of human trials to assess the bioavailability of CoQ10 and also other bioactive compounds.
>> Enhanced dissolution and oral bioavailability of coenzyme Q10 in dogs obtained by inclusion complexation with γ-cyclodextrin
The solubility of coenzyme Q10 (CoQ10) in water is extremely low, resulting in a low oral bioavailability. In this study, we attempted to improve the low dissolution and bioavailability of CoQ10, by means of the complexation with natural α-, β- and γ-cyclodextrins (CyDs) and 2-hydroxypropyl-β-CyD (HP-β-CyD). The complexation of CoQ10 with CyDs was studied by the solubility method. Solid CoQ10/CyD complexes with different molar ratios were prepared by the kneading method using ethanol/water (1: 1) mixed solvent. Among these CyDs, γ-CyD significantly increased the solubility of CoQ10 at lower CyD concentrations. The powder X-ray diffraction peaks of CoQ10 disappeared following solid complexation with γ-CyD, although the endothermic peak due to the melting of the drug did not disappear completely. The dissolution rate of CoQ10 was significantly increased by complexation with γ-CyD, probably due to soluble complex formation and/or nanometer-sized particle formation, which was reflected in the enhanced oral absorption in dogs. The results indicated that γ-CyD is useful for improving the oral bioavailability of CoQ10.
>> Enhancement of oral bioavailability of coenzyme Q10 by complexation with c-cyclodextrin in healthy adults
The objective of this study was to determine the effect of molecular encapsulation of coenzyme Q10 (CoQ10) by complexation with c-cyclodextrin (c-CD) (CoQ10-c-CD) compared with a mixture of CoQ10 with microcrystalline cellulose (CoQ10-MCC) on absorption and bioavailability of CoQ10 in supplement form in healthy adults. Twenty-two volunteers received a single dose of a 150-mg capsule containing 30 mg CoQ10 under fasting conditions in an open-label, crossover design with a 2-week washout period. Blood was collected before dosing and after dosing periodically over 48 hours. Plasma levels of CoQ10 were determined by high-performance liquid chromatography using an electrochemical detector and an online reduction system. After 6 and 8 hours of dosing, there was a significant increase in mean CoQ10 plasma levels of subjects after a single oral administration of the CoQ10-c-CD capsule compared with those with the CoQ10-MCC capsule. In addition, the mean plasma levels at 24 and 48 hours tended to be higher after CoQ10-c-CD administration in comparison with CoQ10-MCC administration. The area under the plasma CoQ10 concentration curve and the maximum plasma concentration (Cmax) values as well as their corresponding log-transformed values, log area under the plasma CoQ10 concentration curve, and log Cmax for the CoQ10-c-CD formulation were significantly higher than those for the CoQ10-MCC formulation. These results indicated that the oral absorption and bioavailability of CoQ10 in healthy adult volunteers could be significantly enhanced by complexation with c-CD, suggesting the potential use of c-CD as a formulation aid for orally administered CoQ10.
