Study Of Percutaneous Characteristics And Transdermal Drug Delivery System Of Anemonin

Anemonin is Pulsatilla camphor obtained from anemone Pulsatilla, Clematis chinensis, Ranunculus sceleratus, Radix Pulsatillae and other ranunculaceae. It is the activity ingredient of those plants and can be used as anti-inflammatory, antitumor and analgesic agent.Anemonin is a white crystalline powder with its molecular weight 192.16 and a melting point near 157~158℃. It is freely soluble in chloroform, hot water and hot alcohol and slightly solubled in cold water. The character of anemonin show that it is fit to develop to the transdermal drug delivery system.Another reason of anemonin is the ideal candidate of transdermal drug is that anemonin's thrill,the one who eat it will feel sick,vomitive etc and it can stimulate the kidney to produce hematuria and albuminuria.All these side effects and first pass effect can be avoided if animonin is developed to a transdermal drug delivery system.And also the transdermal drug delivery system is convenient to be used.The main three parts of the present study are: (1) the preformulation study involving screening the proper enhancers for transdermal absorption of anemonin;(2)extracting and separating anemonin from Clematis chinensis with distillation;(3) to investigate the feasibility of gel as transdermal carries of anemonin.(4) prepare the adhesive-matrix type patches by salivate technology with Eudragit E100 as adhesive-matrix material and prepare the reservoir patches by hot-envelop method with HPMC ethanol gel as reservoir medium to invetigate the transdermal characteristic of them.Anemonin's precursor in plants is proanemonin, that abroadly exists in ranunculaceae.Proanemonin and anemonin can volatilize with water gas because of the lower boiling point of them, so the extrating way of decoction is not selected.The study decided to extract the anemonin from Clematis chinensis with distillation.In the preformulaiton study, the ultraviolet spectrum and HPLC methods for theassay of anemonin were established firstly and then the physicochemical properties, especially the solubility in various solvent systems such as alcohol, PEG400 were examined. With the known physicochemical parameters, the skin permeability of anemonin was predicted using three different predicting models, i.e, simple membrane partition-diffusion model (Pott-Guy model), partition coefficient method and Magnusson model. The predicting permeability was then compared with actual transdermal parameters obtained from the in-vitro diffusion study using human cadaver skin set on modified Franz diffusion cell system, and feasibility of drug transdermal absorption was then analyzed. The results showed that anemonin's solubility was 0.98mg/ml in water and 1.38mg/ml at 37 V .Study on transdermal penetration enhancers(enthnol, propylene glycol,PEG400,azone and oleic acid) showed that the ethanol and azone were good vehicles for transdermal permeation of anemonin. However, the maximum flux was obtained by using the enhancer combination of ethanol(30%) and azone (3%), with which the flux reached to 13.77 ± 0.16μg/cm2/h,but propylene glycol reduced the flux rate of anemonin.Hydrogel comes into being the gel with three-dimensional reticular structure, when the hydrophilic macromolecule compound meets water.The hydrogel is the one of most popular transdermal delivery system in recent years.It has been widely reported that hydrogel has the excellences of high trnsparence, salubrious, unirritative, easily embrocate and easily clean.The study use 30% ethanol to be the menstruum.One reason is that ethanol was the good enhancer,the other is it can make the gel thicker after enthanol volatilizated and easily adhere to skin.The paper investigated the effects of different concerntrations azone on the permeating characteristics of anemonin in HPMC gels vehicle in vitro,we also investigated the effects of different concerntration HPMC and carbomer934 on the permeating characteristics of anemonin in vitro. The results show that there was no differences between 3%azone and 5%azone.And the flux of anemonin through human skin from HPMC gel was 1%HPMC>3%HPMC>5%HPMC, but the changes of carbomer934 have little effect on itOn the basis of above experiments,we choose the best one to observe the anti-inflammatory effects of anemonin gel and discoveredthat the anemonin gel can markly inhibited the inflammatory edema in the ear of mice that is caused by xylene.In the last part of this paper, the adhesive-matrix type patches and reservoir patches were prepared to investigat the transdermal characteristic.The adhensive-matrix prepared by salivate technology with Eudragit El00 as adhesive-matrix material ,and the reservoir patches prepared by hot-envelop method with HPMC ethanol gel as reservoir medium. The formulating factors such as the effects of different concentration anemonin, plasticizers, penetration enhacners (azone, oleic acid) on the physical quality of patches were observed. The in-vitro transdermal performance of the different formulations as well as the anti-inflammatory effects of the anemonin adhesive solution was also studied. The obtained results indicated that Eudragit El00, possessed good compatibility with several other excipients examined in this study. The flux of anemonin permeating through human skin from adhesive-matrix type patches of anemonin was 1.72 ± 0.02μg?cm~2-h~1 and 1.47> 2.3 times higher than from saturated water solution and reservoir patches respectively,but the flux of reservoir patches is lower than saturated water solution and the flux was not affected markly when the concentration of drug was increased. The anemonin adhesive solution can markly inhibited the inflammatory edema in the ear of mice that is caused by xylene too. The adhesive-matrix type patch was effective for transdermal delivery of anemonin and was prepared simply, which has the potentiality to be developed to new transdermal preparation of anemonin.