Study Of Preparation Of Micronization And Pharmacodynamic Of Micronized Shuanghuangpu Hydrogel Hydrogel Patch And Microdialysis For Its Pharmacokinetics

ObjectivesOn the basis of previous studies,the medicinal material was micronized, in order to prepare micronized Shuanghuangpu hydrogel patch with good performance,matrix prescription has been optimized. By comparing the effect of percutaneous absorption and pharmacodynamics of micronized and ordinary powder Shuanghuangpu hydrogel patch,to explore the effect of micronized durg. Microdialysis(MD) combined with LC-MS/MS technique were used to detect the berberine concentration which is the one of the effective component in micronized Shuanghuangpu hydrogel patch. Establishing micronized Shuanghuangpu hydrogel patch transdermal pharmacokinetics in rat animal model,we studied on pharmacokinetic characteristics of micronized Shuanghuangpu hydrogel patch to provide a theoretical basis for the development and application of micronized Shuanghuangpu hydrogel patch.MethodsTo optimize micronized Shuanghuangpu hydrogel patch, we choose the sensory scores as an index for evaluating patch performance. Excipients dosage was selected by the single factor method,for example, sodium polyacrylate, carbomer, gan qianglv, tartaric acid, glycerol and so on. The matrix loading was evaluated with the indexs such as initial adhesion, holding power and sensory scores. Then, orthogonal design was used to optimize matrix formulation, which with the initial adhesion, holding power and sensory score as the evaluation index. The percutaneous rate of berberine was compared between the micronized and ordinary powder of Shuanghuangpu hydrogel patch in vitro to explore the relationship between berberine’s accumulation and powder particle size. Ear phlebitis of rabbit model was established to observe the phlebitis change before and after treatment, observe the pathological changes with the indexs below: venous endothelial cells, thrombus, inflammatory cell infiltration and edem. ELISA was used to study the level of inflammatory factors included E-Selectin, ICAM-1, IL-1β and TNF-α. According to the above experimental results, we compared treatment effect of the two patches. In the pharmacokinetics experiment, microdialysis combined with LC-MS/MS were used to detect the dynamic changes of the concentration of berberine after transdermal delivery in the subcutaneous tissue of rats.ResultsThe performance of patch were improved after prescription was optimized. With berberine as the evaluation index, we found it could pass through the skin, and the accumulative permeation amount increased continuously with experiment time. The effective components of micronized patch has the larger permeability, for the cumulative release amount of 12 h, berberine of micronized patch is 2.6 times more than ordinary powder patch.Pathology results suggested that there were significant difference between the groups of micronized powder patch, ordinary powder patch and blank in the venous endothelial cells and inflammatory cell infiltration. Rabbits were treatmented with micronized and ordinary powder Shuanghuangpu hydrogel patch, the levels of inflammatory factors included E-selectin, ICAM-1, IL-1β and TNF-α were down. But inflammatory level was decreased more in the micronized Shuanghuangpu hydrogel patch.Pharmacokinetics results suggested that the abdomen of the rats were sticking with micronized Shuanghuangpu hydrogel patch, Subcutaneous tissue of the largest drug was(2318.97±238.52)ng/m L, the peak time(Tmax) was(11.13±1.36)h. Maximum plasma concentration(Cmax) was(13.69±2.43)ng/m L, the peak time(Tmax) was(12.00±0.00)h drug absorption was stable, rapid and sustained a long duration.ConclusionsMicronized Shuanghuangpu hydrogel patch has been preparated with good performance after matrix formulation was optimized by single factor and orthogonal design experiments. The berberine of micronized Shuanghuangpu hydrogel patch had faster transdermal rate than ordinary powder Shuanghuangpu hydrogel patch, and cou Ld improve the bioavailability. Micronized Shuanghuangpu hydrogel patch was better than ordinary powder in pharmacodynamics by the evaluation of phlebitis appearance, pathological analysis and pathological analysis. The abdomen of the rats were sticking with micronized Shuanghuangpu hydrogel patch, drug was in the cuticle of the skin,which formed a drug reservoir in order to achieve the sustained release effect.