Oxymatrine Enteric Coated Sustained Release Pellets

Objectives: To prepare OMT enteric-coated and sustained-release pellets with optimal excipients and technologies,to establish research foundation for the development of new OMT dosage form and the research about sustained-release pellets of water soluble drugs.Methods:(1) The content of OMT was determined by spectrophotometric method after colorated by acid stain for establishing the determination method of OMT.(2) The influence of the ratio between water and MCC,extrusion speed, spheronisation speed and spheronisation time were investigated by means of orthogonal design to determine the optimal prepare-technology;The micromeritic properties was determined by the distribution of particle diameter,angle of repose,bulk density and friability.The vetro release effect was evaluated by means of the pellets'release rate in water.(3) The properties of different polyacrylic acid resin were compared in intrinsic viscosity, relative viscosity of coating solution,the spray drop size under the same condition;The bed coating technology was applied to prepare enteric-coated pellets.The bed coating speed,coating temperature,the pressure of spray gun were investigated by means of single factor experiment to optimize the bed coating technology;The oxymatrine enteric-coated pellets were prepared by bed coating techonology with polyacrylic acid resinⅡ,Ⅲ,the release rate of the oxymatrine enteric-coated pellets in simulated gastric juices and in simulated intestinal juices was determined to optimize the enteric-coated excipient.(4) The oxymatrine framework sustained-release pellets were prepared by the extrusion-spheronization method with different specifications of HPMC,EC and MCC, sodium alginate, chitosan, stearyl alcohol,and different adhesives. The disintegration time and release rate in water were determined to evaluate the oxymatrine framework sustained-release pellets.(5) The excipient was optimized by comparing the viscosity of coating solution, the spray drop size under the same condition,the spraying velocity and film-forming time.The oxymatrine coated sustained-release pellets were prepared by bed coating method and evaluated by the dissolution rate in vetro. The dissolution curve was fitted. The optimal preparation technology was determined by investigating the effects of amount of plasticizer, kind and amount of porogenic agent,different coating level by weight on OMT's release.(6) The enteric-coated and sustained-release pellets were prepared by bed coating technology with optimal sustained-release excipient and polyacrylic acid resin ,the dissolution rate in vetro was detected to evaluate the praparation. The dissolution curve was fitted.Results:(1)The acid dye colorimetry was established to determine the content of OMT.The regression equation wsa as follow: m=0.151A-0.0025(r=0.9998),OMT had a liner relationship with the absorbance A in the range of 13μg～117μg .The preparation technology of OMT pellets were optimized by means of orthogonal design: the ratio between water and MCC was 0.90:1, the extrusion speed was 45Hz,the spheronisation speed was 40Hz,the spheronisation time was 7min.The pellets prepared in this condition had good micromeritic properties,the release rate in water within 30min was over 75%, meeting the requirement of speed-release pellets.(2) The bed coating technology was optimized:the bed coating speed was 50r/min,the coating temperature was 30℃,the pressure of spray gun was 0.10MPa(the instrument's pressure). Polyacrylic acid resin huⅢwas optimized to coat the OMT pellets with coating rate of 15% by weight.(3) The disintegration time of the prepared framework sustained-release pellets in water was shorter,the release rate in vetro can not meet the requirement of sustained-release preparation in the chinese pharmacopoeia 2005.The good sustained-release pellets can prepared by coating with EC7 containing 20%DEP, 2%PVPK30. The curve of cumulative drug release was accorded with the first grade equation.The OMT enteric-coated and sustained-release pellets with good dissolution rate in vetro was prepared by the optimal polyacrylic acid resin huⅢand EC7. The dissolution curve was also accorded with the first grade equation.Conclusion:The preparation technology of OMT by means of the extrusion-spheronization method with MCC is determined,the spherical degree, particle diameter, hardness of the prepared OMT pellets are suitable.The repeatability of the technology is good.The bed coating technology can be used to coat pellets in lab.OMT is more soluble in water,depending on framework only, pellets can not meet the requirement of sustained release.After coated with EC,the OMT pellets'dissolution rate shows a good sustained-release characteristics in water.With optimal technologies and excipients by fractional experiment,the enteric-coated and sustained-release pellets are prepared.All these work could establish research foundation for the development of new OMT dosage form.