Optimization Of The Formulation And Process For Hesperetin Micelle And Its Evaluation Of Safety And Efficacy As Cosmetics

Objective:To prepare hesperetin micelle by screening the formulation and optimizing processing technology. And evaluated its quality stability, safety, efficacy as a skin care product. The aim is to provide theoretical basis for formulation development of hesperetin cosmetic applications.Methods:With the help of ethanol as the solvent, glycerin as the moisturizing agent, hyaluronic acid as the stabilizer and moisturizing agent, ethylenediaminetetraacetic acid disodium salt as metal chelating agent,with Tween80 and RH40 using complex manner to prepare hesperetin micelles. Taking Zeta potential absolute value and particle size of the preparation as evaluation index, stirring time, stirring speed, stirring temperature and ethanol, glycerol, hyaluronic acid content in the prescription and surfactant type, content and distribution were investigated on hesperetin micellar stability. Based upon HPLC analysis method,a response surface analysis was derived to screen the formulation and optimize processing technology. The quality stability of hesperetin micelles was evaluated by room temperature, heat and low temperature as well as its pH, appearance, odor, Zeta potential, particle size and drug loading. The safety of hesperetin micelles was evaluated by mouse acute oral toxicity test, skin irritation, sensitization test and human trials.Evaluation of whitening effect is generated by the case of zebrafish embryos melanin in different concentrations of hesperetin micellar solution.Results:The results of stability test by single factor experiment showed that the process and prescription were: Stirring temperature 70 ℃, stirring speed 800 rmp, stirring time 20 min.glycerol content of 3%, the surfactant dose was 3%, with Tween80 and RH40 usingcomplex manner, hyaluronic between 0.3% to 0.5%, ethanol content between 3% to 6%,RH40 and Tween 80 complex to a certain percentage. In the transdermal experiment, the prescription was confirmed by response surface analysis using percutaneous osmosis rate as the index. The results showed that ethanol, hyaluronic acid, Tween 80: RH40 were 6%,0.47% and 4:1, respectively. Under the above condition, the predictive percutaneous osmosis rate of hesperetin reached 8.70187μg·cm-2·h-1 while the the average value of the three sets by test was 8.70473±0.0063μg·cm-2·h-1, two were no major discrepancy. The model is proved accurate and reliable by the method of response surface method. The results of stability showed that hesperetin micelles can maintain the appearance of stability and drug loading in room temperature, high temperature and low temperature.The safety evaluation showed that hesperetin micelles had no toxicity because of its median lethal dose was more than 5000 mg/kg. The score of irritation and allergic about hesperetin micelles were 0, which proved that there was no skin irritation and allergies. Human patch test results were negative. With the change of concentration in the range of 0.2~1μL/mL,hesperetin micelles inhibited the melanin synthesis in zebrafish. It proved hesperetin micelles had whitening effect.Conclusion:Heperetin micelles we prepared by reasonable prescription and simple technique had good quality stability. It looks clear and no bad smell. The evaluation showed that hesperetin micelles had high safety and whitening efficacy. In summary, hesperetin micellar solution as a new type of whitening products, has a certain significance in the field of cosmetics.