Preparation And Pharmacodynamics Of Wuji Gastric Floating Adhesive Micropills

Wuji pills,one of the classical Chinese medicine prescriptions,which is composed of coptis chinensis,radix paeoniae alba and evodia rutaecarpa by the ratio of 6:1:6 and is widely used for the treatment of gastric ulcer and irritable bowel syndrome.In this study,Wuji gastric floating adhesive micropills(WJGP)were prepared by stirringmelting granulation method.The mucosal adhesion,floatability and dissolution of the micropills were evaluated.The central composite design was performed on three factors: the amount of adhesive material(X1),the amount of floating materials(X2),the ratio of carbomer(CP)to hypromellose(HPMC)(X3),the optical prescription was as followed: the drug content was 35%,the amount of binders was 35%,the amount of adhesive material was 21.64%,the amount of floating material was 8.00%,and CP: HPMC was 3:4.After that,the micropills were coated,and the coating prescription was as followed: an ethyl acrylate-methyl methacrylate copolymer aqueous dispersion(Eudragit NE30D)as a coating material,the coating concentration was 10%,and the coating weight was increased by 10%,The amount of talc was 30%.The prepared WJGP exhibited good gastric mucoadhesive property with 85.4±1.29% retention rate in vitro,and good floating characteristics with drift time less than 1 minute and and the floating rate was about 88.6 ± 1.33% after 8 hours.In addition,WJGP could stay in the stomach of rats for 6-8 hours in vivo.Rabbits were administrated intragastrically with WJGP and Wuji pills for pharmacokinetic study.The WJGP conforms to the single-compartment model,which can significantly increase the average dwell time,elimination half-life,and the area under the curve at the time of drug use.Compared with the reference preparation(Wuji pills),the relative bioavailability of berberine was 260.16% and paeoniflorin was 291.47%.It could attribute to that WJGP increase the drug’s residence time in the gastrointestinal tract and improved the drug’s bioavailability.The protective effect of WJGP on gastric mucosa was studied,and the mechanisms of Wuji gastric floating adhesive micropills(WJGP)against gastric ulcer induced by ethanol and acetic acids in rats were discussed.The established rat ethanol-induced gastric ulcer model appeared acute gastric injury,and chronic gastric mucosal injury was observed in acetic acid induced gastric ulcer model rats.The treatment with cimetidine and all the WJGP effectively improved clinical symptoms in rats,reduced ulcer index,increased the activity of superoxide dismutase(SOD),decreased the levels of malondialdehyde(MDA),interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α),thereby alleviated the inflammation of gastric mucosa and promoted the healing of ulcers.In summary,WJGP middle dose was the most effective,that was same to cimetidine,and its efficacy was stronger than Wuji pills of the same dose.Immunohistochemistry analysis revealed that WJGP inhibited nuclear translocation of NF-κB p65.In summary,these results strongly indicated that WJGP exerted a gastro-protective effect against gastric ulceration,and the underlying mechanism might be associated with the improvement of antioxidant and anti-inflammatory status through NF-κB pathway.