| Objective:Colon specific drμg delivery system, mainly including time-controlled release and pH-dependent form as well as enzymes-degradation form, is being extensively investigated in the pharmaceutical area. However, due to the transit time and pH in the digestive tract were effected by food,disease, which result in site-specific of time-controlled release and pH-dependent form was not very good; and the enzymes-degradation form is not influenced by transit time and pH, so more attention has been paid to the enzymes-degradation form in recent years. Berberine Tannate was used as the model drμg, a pH-dependent and enzymes-degradation colon-specific drμg delivery system was developed by using multi-layer coating technology, make drug release in colon.Method: In this article we use the new colon digested material chitosan film as a coat to protect Berberine Tannate tablet from the releasing in the small intestine and the acrylic resin (Ⅱ,Ⅲ) as the enteric coat, meanwhile study the release profiles of Berberine Tannate in vitro.Filling agent,disintegration agent,binding agent have been mixed, prepared into tablets. The disintegration time was used as the index to evaluate the factors and Rx. Select pectin,guar gum,chitosan as enzymes-degradation layer materials,and used the disintegration time as the index,select enzymes-degradation layer materials. Final select the chitosan as enzymes-degradation layer materials.The factors to influence the release profiles have be tested, including the concentration of chitosan(1%,1.5%,2%,), coating weight of chitosan(1.2%,3%,5%), kinds of plasticizers(DEP,propylene glycol,glycerin), content of plasticizer(10%, 20%, 30%).Chose the factors which is more influenced ,carry out orthogonal test, investigation the optimization formula.Take the acrylic resin(Ⅱ,Ⅲ) as the intestine-dissolved layer, investigation the coated tablets of differents coated levels(2%,3%,4%,5%)dissolution rate.This study obtain Berberine Tannate standard curve in the artificial gastric juice,artificial small intestinal juice,artificial colon juice according to the UV spectrophotometry. Results: The formulation of tablets core was decided on the basis of several factors which influencing the rate of release, investigation by the orthogonal test, bulking agent is microcrystalline cellulose,the disintegrant is PVPP, the lubricant is Talc Powder. investigation by the orthogonal test on the basis of chitosan coated level,the dosage of plasticser and the dosage of the disintegrant in tablet core.Chose the coated level is 5%,the disintegrant is 10%, the dosage of glycerol is 20%. The intestine-dissolved layer level is 3%.The standard curve is :A (artificial gastric juice)=0.0232C-0.0008,r=0.9997,linear range:0.25-10μg/ml;A( artificial small intestinal juice)=0.0243C+0.0172,r=0.9993,linear range:6 ~18μg/ml; A(artificial colon juice 2)=0.0242C+0.0023,r=0.9994,linear range:2-32μg/ml.The intra-day inter-day precision is very good, coefficient of recovery fit the bill.The in vitro release rate show that the coated tablets fit the bill in the artificial gastric juice, artificial small intestinal juice, and can release over 85% in the artificial colon juice 2 for 7h.Conclusion: In this study we developed a pH-dependent and enzymes-degradation colon-specific drμg delivery system, which was proved to have good colon targeting property by release experiment in vitro . This coated tablets preparation craft is simple,and can avoid the first pass effect,can increase the compliance ,it's a good kind of dosage forms. So this method is feasible. |
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