Studies On PH-dependent Wanshi Niuhuang Qingxin Sustained-release Pellets

Wanshi Niuhuang Qingxin pills(WSNHQXP) was selected as model drug and the preparation techniques of active fraction of medicinal materials in prescription were investigated. The qualitative and quantitative analysis methods were developed to control the inherent quality of formulation. Based on these results, Wanshi Niuhuang Qingxin sustained-release pellets(WSNHQX SRP) were investigated.TLC methods were used to identify Berberine Hydrochloride, Baicalin, Geniposide in WSNHQX SRP; the method of HPLC for Berberine Hydrochloride, Baicalin, Geniposide were developed to determine their contents in preparation. The concentration of Berberine Hydrochloride and phenolsulfonphthalein in intestine solution and concentration of Berberine Hydrochloride in rabbit plasma were also assayed by HPLC method.The extraction techniques of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Gardenia jasminoides Ellis, Curcuma wenyujinY.H.Chen et C.Ling were optimized by orthogonal experiment design method and single-factor test method, respectively. The b-CD inclusion complex of Zedoary Turmeric oil was formulated by the method of uniform experiment design.Deacetylation degree and molecular weight of chitosan were determined. Chitosan was selected as a material to synthesize hydropropylated chitosan and the effects of alkalization, reaction temperature, time, solvent on degrees ofsubstitution were studied. Hydropropylated chitosan was identified, solubility and intrinsic viscosity were investigated, too.The absorption sites and the absorption kinetics were studied from various intestinal segments ligation using in situ perfusion method in rats. The research demonstrated that Berberine Hydrochloride was poorly absorbed in intestine in general and mostly absorbed in the upper small intestine. The absorption fraction and absorption rate constant were gradually decreased from Duodenum to Colon. The mechanism of gastrointestinal absorption of Berberine Hydrochloride is that the drug transfers to cell via passive diffusion.Wanshi Niuhuang Qingxin pellets with perfect shape and surface characteristics were prepared in a centrifugal granulator by using MCC as filler and 3% HPMC solution as adhesive agent under optimum condition. The dissolution rate of Berberine Hydrochloride meets the demands of preparation.A pH-dependent gradient-release pellet system was investigated by using hydropropylated chitosan and the dispersion system of various methacrylic acid copolymers in water as coater. In vitro experiment makes it clear that various components with different properties are released synchronously.The plasma concentration of Berberine Hydrochloride in three rabbits after a single oral administration of WSNHQX SRP was studied with WSNHQXP as a reference preparation. The results showed that the plasma concentration of Berberine Hydrochloride was steadier and its Cmax decreased significantly, A characteristic of gradient-release was observed in the concentration-time curves of Berberine Hydrochloride of WSNHQX SRP.