The Tripterygium Microemulsion Gel Transdermal Drug Delivery System Design And Evaluation

The traditional Chinese herb Tripterygium wilfordii Hook.f.(TWHF) has been reported to be effective in treating patients with a variety of autoimmune and inflammatory diseases.The oral preparation of the herb is effective especially,but it's side effects all over the body is so serious that limits its use.At present its external preparation has therapeutic effect and few side effects,but the osmosis per cutem is difficult and can't utilized enough.We made the microemulsion as drug delivery vehicles to prepare the transdermal drug delivery systems of TWHF to improve the suffers' acclimatization,reduce its side effects,enrich clinic dosage forms to serve people better.We evaluated the system in vitro and in vivo relatively. The dissertation is summarized as follows:1.Study on dissolvability of extract of TripterygiumThe dissolvability affects the preparation,stability and the pharmacodynamic action and the study of the dissolvability was important for performulation.We studied the method as precipitation,dissolvability of active component and mean diameters and determined the dissolvability of Tripterygium Wilfordii extract in oil phase,surfactant and cosurfactant respectively.The dissolvability of extract in oril phase is as follows:oleic acid,MCT,labrafac, ethyl oleate,IPM,2EHP,Germseal-40 and the dissolvability was better in Tween-80 than in Crempphor 40 for surfactant and dehydrated alcohol for cosurfactant.2.The preparation of tripterygium microemulsionWith the oleic acid as oil phase,Tween-80 and paregal O(1:1) as surfactant,dehydrated alcohol as cosurfactant the optimum formulation was investigated by using titration to prepare the Pseudo-ternary phase diagram,testing the size distribution,stability physico-chemical property, and osmosis per cutem of the microemulsion;the formula of the TWHF was 7.52%Tween-80, 0.84%paregal O 1.1%oleic acid,12.54%dehydrated alcohol,77.50%water,0.5%the extract and the osmosis per cutem of the microemulsion is significantly higher than the ointment in vitro.3.The preparation technique of tripterygium microemulsion gelThe viscosity and the shape were determined to select the adjuvant of the gel and Carbomer 934 was chosen for its suitable viscosity and characteristics.The dependence of apparent viscosity of Carbomer gel from various concentrations on shear rate was studied by rheometer,and discuss the influence of drug to the carbomer gel's rheology property.The results are the higher carbomer content,the higher apparent viscosity of carbomer gel,and after addition the drug,the apparent viscosity of carbomer gel decrease.The Franz diffusion cells were utilized to characterize the permeation behaviour of triptolide in microemulsion gels and the results is 2.5%azone can remarkably enhance the percutaneous absorption of triptolide in vitro.The selected formulation of the tripterygium microemulsion gel is:80%tripterygium microemulsion,17%carbomer (concentration is 3%),0.6%trolamine,2.5%azone.4.Quality Evaluation of tripteryginm mieroemulsion gel in-vitroThe character,identification,examination were studied and the quality control of the preparation by the character,pH value,viscosity was determined according to the experimental results.Determination of in vitro Percutaneous Rate and in vitro of Release of the preparation were did in use of the Franz diffusion cell and the gel permeated in vitro at the speed of 2.6378μg/cm²Â·h by first-order kinetics.The skin irritation test was performed on the skin of rabbit and result was the microemulsion gel had no irritation to the intact skin of rabbits,but the mild irritation to the damaged skin was observed.The content of triptolide was 0.28mg/g in HPLC As the result of the stability test shows,the gel stability is good after storing at room temperature for 6 months and the appearance,content,viscosity and permeation rates had hardly any change.5.Quality Evaluation of Tripterygium Microemulsion gel in vivoThe analgesic effect was studied by using acetic acid-induced wringing text and the result was the aspirin group,Tablet of Tripterygium Wilfordii,Microemulsion gel of Tripterygium high dose group and middle dose group could inhibit body's turning reaction times significantly compared with model group(p＜0.01);So its manifests a positive correlation in effect with the dosage. Between the middle and high dose group of Microemulsion gel and the the aspirin group in analgesic effect was found no significant difference,so its manifests the analgesic effect of the preparation was very good and the middle dose was efficient.The model of arthritis was developed by Freund's complete adjuvant and the inhibitory effect of Microemulsion gel on the rat's foot swelling was determined in the rats with arthritis.The result illustrated that the preparation could exert therapeutic effect on primary inflammation and preventive effect on secondary inflammation in rats with arthritis induced by Freund's complete adjuvant,and its manifested a positive correlation in effect with the dosage.The preparation could decrease the renal toxicity of Tripterygium.The result of the experiment on acute toxicity indicated that Microemulsion gel could decrease the side effects in some degree and keep therapeutic effect.Then we could predicate that transdermal drug delivery system was a good way of lowing the side effects of Tripterygium.We established a method for the determination of triptolide in rat plasma by HPLC/MS and studied pharmacokinetics of Microemulsion gel and Tablet of Tripterygium in rats by transdermal and oral administration respectively.The outcome indicated that the patch was a two-compartment model,and its druggery dynamics parameters were:Tmax=6.667±1.633h,Cmax =82.963±17.626ng/ml,T_1/2(Ka) = 0.39±0.384,T_1/2(α) = 7.314±7.869h,T_1/2(β) =56.7172±26.5155h.The above means that this drug has the advantange of lang time keeping stable blood-drug concentration and steady effects.6.Study on the LCs cellATP enzyme method is deployed to detected the epidermal LC of the mouse.Two different epidermis disjunction methods are used:EDTA and dispase,the result suggests that dispase method is better.