Study On Coenzyme Q10 Self-microemulsifying Drug Delivery System

Co-Q10 is an antioxidant presented in most eukaryotic cells, which is a vital coenzyme in cellular respiration and metabolism. Moreover, it is the energy resource of heart. CoQ10 is widely used as the nutrition supplementation in food, health care pharmacy, and make ups. However, because of its lipophilicity and large molecular weight, the oral bioavailability is low. So it is emergent to find a new drug delivery system for Co-Q10.Microemulsion drug delivery system is thermodynamically stable, of which, the mean particle size is no more than 100nm. Recently, a new drug delivery system is emerging, which is the mixtures of oil, surfactant and co-surfactant. It can be orally administered in soft or hard gelatin capsules and form relatively stable o/w emulsions (the mean particle size is between 10nm and 100nm) owing to the gentle stir of the gastrointestinal fluids. It is defined as self-microemulsifying drug delivery system (SMEDDS). Since the first product Sandimmun Neoral(?) (cyclosporin A) of Novartis was successfully marketed, the study on SMEDDS was strongly promoted.This research was aimed at developing a Co-Q10 self-microemulsifying drug delivery system. Ternary phase diagram was used to identify the microemulsion region. The optimum formulation was established as MCT (27%), RH-40 (46%), PEG 400 (27%), coenzyme Q10 (5%). Physicochemical properties of SMEDDS were studied. The results showed that the mean particle size was 46.1nm (PI was 0.0303), and the zeta potential was -0.03mV. Because SMEDDS disintegrated mainly in stomach, we chose O.lmol/L hydrochloric acid as the disperse phase and used small vessel method (25rpm) to study the method of emulsifying, which could examine the consequence of emulsifying sufficiently. The dissolution test showed Co-Q10 SMEDDS could release rapidly, and the cumulative release percent within 20min in 0.1mol/L HCl and in pH6.8 PBS was 78.00% and 87.11%, respectively.After storing 10 days in 4℃ and 60 ℃, the mean particle size and the content of Co-Q10 SMEDDS were examined and the results proved that Co-Q10 SMEDDS was stable in 4℃, but unstable in 60℃. After storing 6 months in room temperature keeping away from light, the mean particle size and the content of Co-Q10 SMEDDS were almost the same as it was first prepared.Using MDCK cells as the model cells to evaluate the cytotoxicity of SMEDDS by MTT assay. The result demonstrated that SMEDDS had low cytotoxic effect, and 370μg/mL was used for further experiments. The result of cell uptake investigation showed the uptake percentage in MDCK cells was about 10.36% for SMEDDS while just 2.21% for the mix of oil, surfactant and co-surfactant.For the study on in vivo pharmacokinetics behavior of Co-Q10 SMEDDS, male Sprague Dawley rats were used. A RP-HPLC method was established to determine the concentration of Co-Q10 in plasma. Compared with Co-Q10 soft capsule, the relative bioavailability of Co-Q10 SMEDDS was 1.42-fold higher, which contributed to the improved transport efficiency. Moreover, the fluctuation of Cmax is lower than Co-Q10 soft capsule, which was crucial to the safety of patients.