Study Of Baicalin Colon-targeted Granules Based On Plasticizer Dry Powder Coating Technology

Scutellaria baicalensis Georgi is one of the commonly used traditional medicines in China with a long history.Ancient records and modern studies have shown that Scutellaria baicalensis Georgi has therapeutic effects on colitis.BA,as a flavonoid extracted from Scutellaria baicalensis Georgi,has various pharmacological activities such as anti-inflammatory and anti-tumor,and BA has been widely studied due to its advantages of good efficacy and low side effects.In order to reduce the dose and improve the efficacy of BA in ulcerative colitis(UC).In this study,BA was used as the active drug to prepare BA colon targeting granules(EBCGs)by the plasticizer dry powder coating technique.The EBCGs were characterized and evaluated for in vitro and in vivo targeting,and the efficacy of EBCGs in the treatment of 2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced UC in rats was evaluated.(1)Through single-factor analysis,the best prescription process was initially determined by using coating efficiency and in vitro release as evaluation indexes:triethyl citrate(TEC)as plasticizer;alternate addition of coating powder and plasticizer;coating pot speed of 10 r/min;30% talc in coating powder;a 7:3 weight ratio of coating powder to core particles;the plasticizer contains 10% isopropyl myristate(IPM)as an auxiliary plasticizer;a 1:2 plasticizer-to-powder ratio;a curing temperature of 80 ℃;and a curing time of 3 h.The amount of coating powder,the ratio of IPM in plasticizer,and the ratio of plasticizer to coating powder were investigated based on the results of a single-factor study combined with Box-Behnken Design(BBD)response surface analysis,using the coating efficiency and the cumulative release in artificial small intestine and artificial colon solutions as evaluation indexes.Based on the experimental results model to give the best prescription process and according to the actual operation,the percentage of IPM in the plasticizer was finally determined to be 13%,and the reproducibility of the optimal prescription process was good.(2)In this study,particle size analysis,SEM analysis,IR scan analysis,content determination,in vitro and in vivo targeting evaluation,and influence factor experiments were performed on EBCGs prepared by the optimal prescription process.The results showed that more than 80% of our prepared EBCGs were concentrated between 14 and 18 mesh sieves,and all of them were between 10 and 24 mesh.SEM results showed that the coating of BA granules(BGs)with ES100 could be achieved under the optimal prescription process by using plasticizer dry powder coating technology,and IR results showed that ES100 and BA were compatible and would not undergo structural changes under the optimal prescription process conditions.The in vitro dissolution experiments showed that the cumulative release of BA in artificial small intestinal fluid was less than 20% and nearly 90% in artificial colonic fluid,while the in vivo imaging test results showed that the release of EBCGs started only when they reached the end of the small intestine and colon in rats,further verifying the good colonic targeting of EBCGs.The effect factor experiments showed that the EBCGs prepared in this study were more stable under high temperatures,high humidity,and strong light,and the release characteristics were almost unaffected.(3)In this study,the efficacy of EBCGs was investigated in a rat UC model induced by a TNBS enema.The results of the study showed that the modeling was successful and scientifically feasible for use in this study.The colon length of rats in the EBCGs treatment group in the study was better than that of the BA API and positive drug groups,and there was no significant change in the colon’s appearance compared with the control group.The results of both the colonic thickness index and the CMDI score of rats indicated that the therapeutic effect of EBCGs in the low,medium,and high dose groups was significantly better than that of the BA API group,and the efficacy of the medium and high dose groups was significantly better than that of the positive drug group.The histological characteristics of colitis in rats with EBCGs low,medium,and high were significantly improved,and the results were significantly better than those of BA API and positive drug groups.These results suggest that the use of EBCGs for the treatment of ulcerative colitis in rats can reduce the oral administration dose of the active drug BA and improve efficacy.In summary,ES100 is suitable for the preparation of EBCGs by the plasticizer dry powder coating technique.The preparation method is simple,and the prepared EBCGs have good in vivo and in vitro colonic targeting properties and good stability.In addition,the prepared EBCGs can reduce the oral administration dose of BA and improve the therapeutic effect of BA on UC in rats.This study provides reference value for the application of plasticizer dry powder coating technology in related fields and the research and clinical application of BA.