Preparation And Quality Control Study Of Isoniazid Rifampicin And Pyrazinamide Tablets

The tablets is combined by isoniazid , pyrazinamide and rifampin and it is mainly applied to consolidate stage in the short time chemotherapy plan of the first two months. Isoniazid, functioning together with rifampin, can kill lots of tuberculosis bacterium in flourishing metastasis, which makes sputum bacterium negative .While at the same time, pyrazinamide can kill a great deal of semi-dormant germ growing up in acid or neutral environment in order to control its recrudescence. The combined preparation can kill various kinds of germs which lead to tuberculosis.Rifampin which has different crystal structures hasn't good stability in hot or wet conditions and has bad dissolution in water. Isoniazid with its different crystal structures makes different stability and bioavailability. Pyrazinamide has light proportion and static. We studied the exipients and the formulation on the basis of many tests, the result of preparation procedure was powder press tablet directly and film coating technics.Further, we studied its quality control. Physicochemical constant was determinedaccording to the method of ChP 2000.The HPLC and UV had been determined as themethods in the drug dissolution ,The results showed that limitation of the tablet was 80%during 20 minutes. We established an RP-HPLC method for determining content ofisoniazid , pyrazinamide and rifampin in tablet. For assay the linear range of isoniazidwas 0.013 ⁰.06 g.L^-1 and that of pyrazinamide was 0.04⁰.18 g.L^-1 as that of rifampinwas 0.04—0.22g.L^-1.For the average recoveries of methodology isoniazid was 99.3%(RSD0.30% ) and pyrazinamide was 99.2% (RSD 0.28%) and rifampin was 99.2%(RSD 0.6%) .In the study we investigated the stress testing and accelerated testing and found that the tablets is instable in high temperature and high humidity conditions, So we took cover film process. It showed stable quality according to 40℃ and 75%(r.h.) after three months'testing.Acute toxicity showed that LD50 values of mouse oral the combination tablet was 3230.6mg/kg with fiducial limits of 2899.6—3599.4mg/kg (P=0.95) . LD50 values of mouse celiac injection combination tablet was 1360.6mg/kg with fiducial limits of 1273.6-1453.5mg/kg (P=0.95) .