The Study Of Suitability In Prepation Of Compound Phamaceutic Tablet Of PH Sensitive-enzeme Triggered Granule Of Rhubarb Total Anthraquinones For Oral Colon-specific Drug Delivery

Rhubarb is one of the most widely used chinese medicine,the rhubarbanthraquinones is the main material basis of its cathartic effect,to adapt tothe modernization of traditional chinese medicine preparation,the free anthr-axquinones was achieved,whose content is more than50%.However,the freeanthraquinones have no or weak cathartic effect when it was used by oralroute,because it wasmostly destroyed before reaching colon.Therefore,withEudragit L100/S100as pH-dependent materials and CTS as bacteria-dependent materials, the coated granule was prepared with an inner bacteria-dependent layer and an outer pH-dependent layer in a fluidized bed coater,respectively,the results of drug release in vitro indicated good features ofcolon-specific delivery.And then,with San-Huang dispersible tablet asmodel,studied the suitability of coated granule in it.In addition,discussed themethodology of studying drug release in vitro of enzeme triggered preparationfor oral colon-specific drug delivery.Objective:To prepare the pH sensitive-enzeme triggered granule of rhubarb anthr-aquinones for oral colon-specific drug delivery,to study its suitability insan-huang dispersible tablet, to discuss the methodology of studying drugrelease in vitro of enzeme triggered preparation for oral colon-specific drugdelivery.Method:(1)Develop the HPLC method for determination of the content andrealease of rhubarb anthraquinone.(2)The central granule was prepared by high-speed mixing granulatormethod,with the formability and release behavior in colon juice within2hoursas influencing factors,the formulation was investigated by monofactorial study;with Eudragit L100/S100as pH-dependent materials and CTS asbacteria-dependent materials, the coated granule was prepared with an innerbacteria-dependent layer and an outer pH-dependent layer in a fluidized bedcoater, respectively; the influences to drug release of formulation of each layerwere investigated by release behaviors in vitro by monofactorial study,suchthe king and amount of materials of coating and plasticizers.(3)The new san-huang tablet was prepared by RTA-OCDDS,instead ofthe former granule which was not perfect,The effects of the kind and mount ofpressure-buffer accessories and hardness of tablet were invested to study thesuitability,based on the results of realeae behavior before and after compress-ing by f2,the optimal formulation was achieved.(4)The condition of colon was simulated by cecal content, the accumu-lation realease ratio was detected with or no N2, the result was evaluated bytwo-samble T test with SPSS17.0and f2.After that, the effect of N2to realeasebehavior was evaluated.Result:(1)Methodological study shows that the methods were reliable,can meetanalytical requirement.(2)The formulation of central granule was RTA:MCC:PEG-6000:CMS-Na=1:4:1.2:0.4,with3%HPMC(including2%PEG-6000) as adhesives, the acc-umulation realease ratio was86.63%in gastric juice within2hours;Theoptimum formulation of inner enzeme-triggered layer was1.2%concentrationof CTS,40%plasticizer amount of glycerol, and350ml of coating fluid,50℃of curing temperature,6h of curing time; the optimum formulation of outerpH-dependent layer was3:1proportion of Eudragit L100/S100,3%concentration of Eudragit, and25%plasticizer amount of DEP,350ml ofcoating fluid,25℃of curing temperature,0.5h of curing time; theaccumulation leakage ratio from coated granule were6.15±0.64%（±SD，n=3）in gastric juice within2hours and12.33±1.93%（±SD，n=3）in smallintestinal juice within4hours, and the accumulation release ratio was 72.63±2.22%（±SD，n=3）in colon juice within4hours,which indicatedexcellent colon-specific property.(3)There was a great effect of the kind and mount of pressure-bufferaccessories and hardness of tablet to the release behaviors after theRTA-OCDDS being compressed.Withing adding25%pressure-bufferaccessories of MCC:PVPP=2:1,7±0.5kg of hardness,the RTA-OCDDS couldremain former and excellentcolon-specific property after being compressed,the f2=84.64.(4)There was no statistical difference between with or no N2whendetecting theccumulative release ratioin colon juice,thef2=79.63, whichindicated that the oxygen-free environment maybe not essentialcondition.Conclusions：Through adjusting the kind and mount of pressure-buffer accessories andhardness of tablet，theRTA-OCDDS was suitable to the requirement of theprocess of compressing.