Studies On Coenzyme Q₁₀ Loaded Submicron Emulsion For Injection

Coenzyme Q₁₀(CoQ₁₀) is one of the fat-soluble quinone compounds, which are widelyexisted in organisms. It plays a key role in mitochondrial oxidative phosphorylation andATP production. CoQ₁₀is mainly used for the adjuvant therapy of cardiovascular diseasesand hepatitis in clinical. CoQ₁₀can be oxidized and light degraded easily, so the useful lifeof commercial injection is short. In addition, crystallization will happen during the storagetime because of its insolubility. Therefore, heating is necessary to make the precipitationdissolved before administration.In this article, a CoQ₁₀loaded submicron emulsion injection was developed. Iteffectively solved the problem of crystallization, and partially improved the light stabilityof CoQ₁₀. Details are as follows:（1）HPLC methods were established to determine the content of CoQ₁₀in raw materialand submicron emulsion injection. Studies showed that the methods’ specificity andlinearity were good （range of5¹00mg/L, R2=0.9996）, and the recovery was96.6¹03.8%, RSD<0.5%. They met the requirements for determination of bulk drugs andpharmaceutical preparations.（2）Optimized prescription was0.625g CoQ₁₀,5g soybean oil,3g TPGS,2.25gglycerol,0.05g sodium oleate,89.075g water for injection. Technological conditionswere optimized, they were emulsifying temperature （60℃）, high shear speed （3500rpmfor5min）, high-pressure microfluid pressure （1200bar for8cycles）, filtration sterilization（0.22μm membrane）.（3）The particle size, PDI, zeta potential of submicron emulsion were79.10±0.422nm,0.140±0.018,-16.2±1.28mV respectively. Encapsulation efficiency of CoQ₁₀wasnearly99.578%, which was measured by centrifugal ultrafiltration method. DSC and XRDanalysis showed that CoQ₁₀in submicron emulsion was probably amorphous.（4）Stability studies of influencing factors found that submicron emulsion injectionsignificantly improved light stability of CoQ₁₀, but compared with ethanol solution ofCoQ₁₀, the submicron emulsion was more sensitive to high-temperature; Accelerated stability studies showed that particle size of submicron emulsion hardly changed in darkplace under30℃after six months, while the zeta potential and drug content decreasedobviously.（5）HPLC method was established to determine the content of CoQ₁₀in rat plasma.Studies showed that the methods’ specificity and linearity were good （range of0.2¹0μg/mL, R2=0.9999）, and the recovery of CoQ₁₀was86.9%¹04.1%, RSD<6%, while therecovery and precision were88.8%and7.5%at the lower limit of quantification. Themethod was suitable for the detection of CoQ₁₀in plasma samples.（6）Pharmacokinetics of CoQ₁₀solution and CoQ₁₀submicron emulsion in rats werestudied. The plasma concentration-time curve was fitted using kinetica4.4software. Theresults showed that CoQ₁₀in two groups both met two-compartment pharmacokineticmodel in rats. Statistical analysis by t-test showed MRT and K12of submicron emulsiongroup were lower than solution group with significant differences.