| Objective:Colon targeted drug delivery system is a kind of drug delivery system which is through keeping the tablet as a whole while in the upper digestive tract, and disintegration or erosion and release the active drugs when it go through the colon. So this drug delivery system can give drugs to the local or total therapeutical effect of human being. Based on different drug release principle, this system can be divided into three kinds: pH-depended drug delivery system, time-controlled drug delivery system and colon-specified germs triggered-type drug delivery system. In this study, in order to achieve the colon-targeted drug delivery, we established dry-coating tablets of indomethacin, which depended on the common advantage between pH-depended drug delivery system and time-controlled drug delivery system.Method: The preparation of coating tablets: we screened proper excipient, which is based on pre-experiment. Then we got quick release and high expanding property tablets core by orthogonal experiment design. And use Hydrogenated Castor Oil andEthylcellulose and others hydrophobic impeded material as well as PEG 6000 to make time-controlled system and through dry-express coating method to make coating layer in order to control the release time at three hours. Outer of the dry-expressed coating layer, we added film-coating material that can dissolve at pH 4.5 to 5.0, so the drug release system could dissolve in dodecadactylon. After that the dry-expressed coating layer was exposed to intestine fluid. When get to the colon after about three hours, the tablet core sucked water expand, as the result, the coating layer was disrupted and the drug was released quickly. The method of assay: We got the standard cure equation when the concentration is 0.004 to 0.04mg/ml by UV spectrophotography. In this way, we can assay the content of indomethacin colon-targeted tablets. Dissolution test: Through the experiment, we examined the different dissolution methods. At last we certificated the method of cylindrical basket at 100r/min is equal to the method of paddle at 50r/min in Chinese Pharmacopeia. Regard to the gastrointestinal motion is fairly slow in human being, at the end we employed the paddle method at 50r/min to determination the dissolution of drug. The dissolution test is carried about in artificial gastric juice for two hours, then in pH 6.8 artificialintestine juice, we collect the sample in different time point and assay them by UV spectrophotography. At three hours, the drug began to pulsed release. In vivo test: we use the New Zealand rabbits to verify the time lag in vivo of indomethacin colon-targeted tablets. We divide the rabbits into two groups randomly. One group was given the tablet core; the other was given indomethacin colon-targeted tablets. Then we collect the blood in different time point and assay the blood concentration of indomethacin by RP-HPLC. The test of stability: at the condition of 40±2℃, RH: 75±5%, we checked the external appearance, assay and dissolution rate. We exammed 0, 1, 3 months.Results: The method of assay: the standard curve equation is well in the range of linear relation. And the adjuvant and coating material have no interaction to the assay. The content is between the 100%±7.0%. The dissolution rate test: Through the assay of the result of different time samples, certificate the formula of dry-expressed coating layer is reasonable, and can keep the time lag to three hours. So the method can achieve the expected colon-targeted drug release. The in vivo test in rabbits: From the chromatigram, we can find the peak of internal standard; the sample and other things can be separated properly. The linearrelationship is well in the range of 0.2 to 20μg/ml of blood drug concentration, r=0.9943, n=7. The equation is R=0.4157+0.9411C. From the fig of blood drug concentration-time curve, we can find that the time lag is very short in the control group which was given the tablets core. While the time lag of the t... |
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