Study On The Preparation And Serum Chromagraphy Of Wuji Gastric-floating Pellets

Wuji pills was recorded in ―a New Book of Pediatrics, a medical work of pediatrics‖ for the first time in song dynasty, and was described in ―pharmacopoeia of China(2010)‖. The prescription was composed of coptis chinensis, radix paeoniae alba and evodia rutaecarpa according to the proportion of 6:6:1. It has been used to smooth the liver, ulate the spleen, clear heat and harmonize the stomach for a long time, and is frequently ultilized for the therapeuty of digestive system disease, including irritable bowel syndrome and peptic ulcer et al, in modern times. The treatment and the effect of it is remarkable. Commercially available dosage form for Wuji pills are traditional pills, of which the gastric rention was limited influenced by gastric emptying and intestinal transit. Therefore, the traditional Wuji pills can not provide efficient and sustained local gastric-targeted therapeutic effects. In this study, our aim was to develop an gastricfloating pellet that can improve local treatment drug concentration and posses high bioavailability to make up the shortcomings of traditional pills. In the end, relevant evaluation of the gastric-floating pellet was carried out.First of all, Wuji pills was extracted by the traditional method. In the study, the bacteriostatic activity of extracts and the extraction rate of index component were adopted as comprehensive evaluation index. Staphylococcus aureus was the indicator bacteria, and paeoniflorin, berberine and evodiamine were the index component. Central composite design/response surface method based on single factor test was employed to optimize variables, and the mathematical model was established. The extraction technology was simple, economic, low toxicity, and the established mathematical model was predictive. The final determined parameters for the extraction was as follows, the ethanol volume fraction was 80.5%, the liquid-solid ratio was 8.3 m L·g-1, the extracting time was 38 min, the extracting frequency was twice.Secondly, the reform of Wuji pills was conducted ultilizing the floating drug delivery system. The final new dosage form was a multi-unite dosage form, gastric-floating pellets with a light drug-loaded effervescent inner core and a retarding film. In the study, the inner core was manufactured by melt pelletization, which was free of solvent and pelletization cycle was short, the outer film was coated by a fluidized coating-machine. In vitro floating characteristic and drug release property was adopted as the evaluation index. Central composite design/response surface method based on single factor test was ultilized to optimize variables of the inner core formula and the mathematical model was established. The optimal inner core can float for a long time and release the index component neatly. Coating formula was optimized by single factor test, and the drug release property was adopted as the evaluation index. The optimal pellet can float for more than 8 hours in vitro and release the index component constanly for 8 hours in vitro. Drug release accorded with Hixson-Crowell equation. The final determined inner-core and coating formula was as follows: the proportion of glycerol monostearate and octadecanol was 7:6, the dosage of binders was 66.5%, the dosage of calcium carbonate was 8.5%, the dosage of HPMC K100 M was 7%; coating weight gain was 10%, polymer content was 10%, the dosage of talcum powder was 50% of the mass of polymer.Finally, serum fingerprints of Wuji gastric-floating pellets in rabbits was studied. The pellets were delivered to rabbits by intragastric administration, and serum was got at various time-points and analysed by HPLC to gain the serum fingerprints after treatment. Compared with the chromgraphy of blank serum and pellets sample, we found that the recognited chromatographic peak of the constituents of the pellets absorbed into blood was a total of 28, and 7 of them was archetype, the rest was supposed as metabolite. In addition, paeoniflorin, berberine and evodiamine were known archetype, and the other four unkown archetype were derived from ―sovereign drug‖ coptis, which should be validated by HPLC/MS in the future.