| Background and Objective: OCDDS(Oral Colon-specific Drug Delivery System) is a kind of drug target delivery systems, which can deliver drug at colon. At present, there are several kinds of OCDDS: pH-sensitive system, time-lag system,bacterium-sensitive system ,time-lag combined pH-sensitive system. They all have same benefits and shortcomings. The pH and transfer time of gastrointestinal tract sometimes change for different food and different person. The stomach transfer time is much unstable and it always takes two to six hours to transfer drug through stomach to intestine. But the intestinal transfer time is relative stable and it always takes about three hours transfer drug via intestine .From previous reports ,we always take it for granted that the pH of colon is the most high site of the gastrointestinal tract, but from recent reports ,the pH of colon is not the most high site of gastrointestinal tract,because bacterium degrade the organic in the colon and acid is released and lead to low pH which is about 6.5. From recent reports, we confirm that the pH of duodenum is about 6.8, the mean pH of jehunum is 7.4 and the pH of colon is about 6.5. Bacterium-sensitive system always deliver drug slowly and lead to low bioavailability. As a result, we designed a new kind of oral colon-specific pellets using hydrochloric levofloxacin as a model drug to guarantee delivery of drug at colon. Methods:Through orthogonal experiment design, using blank pellets and floating-bed, we prepared OCDDS pellets by coating four layers. From interior to exterior, they are drug layer, block layer, time-lag layer and pH-sensitive layer. In vitro experiment, dissolution behavior of every sample was studied .The lag time was obtained from the dissolution curve. At the same time, we have studied the effects of the weight increased of block layer, time-lag layer, pH-sensitive layer, the pH of dissolution medium, the ion intensity of dissolution medium and different rotation rates on the dissolution rate and the lag time. In vivo experiment, The A2B1C2 pellets were administrated orally to dogs and blood samples were got, a week later, the pellets were administrated orally to dogs again and dogs were dissected at different time to determine where the pellets dissolved in gastrointestinal tract and contents of gastrointestinal tract were got, then HPLC method was established to determine the concentration of levofloxacin in the blood and in the contents of gastrointestinal tract. Results:From orthogonal experiment design, we got the most excellent formulation A2B1C2. In the three factors, the weight increased of time-lag layer is the most important factor effecting the lag time. The weight increased of pH-sensitive polymer layer is the second important factor and the weight increased of block layer less important factor effecting the lag time. As the weight of time-lag layer and pH-sensitive layer increased, the lag time is longer. The pH of gastrointestinal tract has same effects on lag time. At the most high pH condition, about 63% of drug delivered in colon artificial juice after 5 hours .At the lowest pH condition, almost all pellets begin to deliver drug after 5 hours but the dissolution rate was decreased. As the ion intensity increased, the drug was released more rapidly and lag time is shortened. After effect factor experiment, lag time and dissolution rate were less changed. From the animal experiment, the concentration of levofloxacin in the colon contents is most high at 5.5 hours. The mean lag time in body is 4.6 hours and Tmax are 5.8-9.1 hours .Conclusion: The hydrochloric levofloxacin OCDDS pellets we designed can deliver drug at colon.
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