Establishment, In Vitro And In Vivo Evaluation Of8-MOP Microemusion And Its Microemulsion-based Hydrogel

OBJECTIVESVitiligo is a skin disease with spontaneity hypopigmentation, and is a world-class Persistent ailment like Psoriasis. Psoralen is the fruit of Legume Psoealea corylifolia, which has repigmentation effect and can treat vitiligo. Now mainly used in clinical is its active ingredient,8-methoxyposoral (8-MOP), whose topical preparations have better efficacy. Since there are several side effects when use8-MOP topical preparations to treat vitiligo, we need to retain the drug in the treat target site (epidermis) and reduce its quality in blood circulation. This research based on the stability of microemusion, and prepared8-MOP ME and MBH, then studied in vitro and in vivo permeation experiments. The goal of this research was to develop good efficacy, low toxicity and convenient topical preparations.METHODS AND RESULTS1. Selected o/w microemusion prescriptionsThe analytical method of8-MOP was set up and the standard curve, linear range, precision and recoveries were all meet the requirements. Selected2cosurfactants,3surfactants and5oils and mixed with water in different proportions to from microemusion. Prescriptions had best stability were chosen to load drug, then selected3drug loaded prescriptions for next experiment.2. In vitro transdermal study of microemusions and quality evaluationThe method of in vitro transdermal study was established. The permeability of prescription4,prescription8, prescription9and solution were determined using a modified Franz-type diffusion cell fitted with abdominal skin of excised anthony pig. The results showed that the permeate rate of prescription8was0.39±0.022μg/h·cm2, and the lag time was2.5±0.230h. There were no statistically significant difference between prescription8and8-MOP solution. Significant difference in the skin residual amount of solution and prescription8was observed at time of24h (P<0.01), and prescription8had biggest retention transdermal ratio1.67±0.32. Chose prescription8as optimal8-MOP ME prescription and its quality assessment was performed. The results showed the appearance, particle size and stability met the requirement.3. Establishment of8-MOP MBH and in vitro transdermal studyThe gel formulation was composed of Carbopol940as substrate, glycerine and1,2-propanediol as humectant, ethylparaben as preservative. A series of in vitro quality assessment was performed and the results met preparation requirements.8-MOP ME as control and the in vitro transdermal and release experiments were performed. The results showed that when8-MOP ME formed MBH, the permeate rate and in vitro release rate didn’t change (P>0.05), and the lag time prolonged while the skin residual amount reduced (P<0.01).4. In vivo transdermal study of8-MOP ME and MBHFemal rats were used as experimental model and in vivo transdermal study of8-MOP ME, MBH and commercially available solution were performed. After topical administrated preparation, blood samples were withdrawn from the fossa orbitalis of rats at predetermined time intervals, and after last blood sampled, cut off skin.8-MOP in rat plasma and skin was determined by HPLC. The results showed that AUC(0-24) of8-MOP ME was2.9times than8-MOP solution, while the skin residual amount was4.9times than8-MOP solution. Namely8-MOP ME relatively improved the drug skin residual amount. AUC(0-24) of8-MOP MBH was2.8times than solution, but the skin residual amount had no difference (P>0.05). So8-MOP MBH had no skin targeting.CONCLUSIONS Both in vitro and in vivo transdermal study showed8-MOP ME could improve the retention and transdermal ratio and had some skin targeting compared with8-MOP commercially available solution. But when prepared into MBH, although its permeate rate and in vitro release rate didn’t change, the drug skin residual amount reduced,which means8-MOP MBH didn’t have skin targeting.8-MOP ME can be considered to make into sprays.