Study On The Stability Of Rifampicin Injection And Rifampicin Liquid Preparation

Rifampicin（RIF）is the most effective drug of choice for the treatment of tuberculosis at present.However,RIF is often reported to have bioavailability problem that raise the question of therapeutic failure of the current treatment.The probable reason for the poor bioavailability of RIF may be that RIF degrades faster under acid conditions,which results with 3-formylrifamycin, an acid degradation product of RIF by the first-order reaction.Therefore,RIF injections were systematic designed and prepared.To establish a rapid,sensitive and reproducible HPLC method for determination of the content and related substances of rifampicin injection using monolithic column.A Chromolith performance RP-18e（100mm×4.6mm）was used with the mobile phase of[acetonitrile-0.075 mol·L^-1KH₂PO₄-1.0mol.·L^-1citric acid-tetrahydrofuran（V:V=40:90:10:3）]-methanol（V:V=3:2）, the flow rate was 2.0 mL·min^-1;the detection wavelength was set at 254nm.Using this method, rifampicin and its related substances could be absolutely separated.The calibration curve was linear in the concentration range of 6～600μg·mL^-1（r=0.9998）.An average recovery was 100.0%（n=9）.In the systematic preformulation study,the solubility of RIF in some kinds of solvent was investigated,and degradation rates of RIF in different solution with different pH value were also determined.The results showed that the stability of RIF in semi-polar solvents is better than polar solvents,storage period of RIF in propylene glycol solution with pH 8.30 can be achieved in 1213.27h,provide references for the dissolvent choice of RIF injection.Based on the results of single-factor tests about supplemental agent（antioxidants, antioxidant synergist,pH regulator）of RIF injection,the amounts of different excipients were determined.The formulation of injection was optimized on the basis of three factors and three levels orthogonal design by evaluating the cumulative percent of related substance of RIF in 40℃,60℃for 5 days and 10 days.RIF injections were prepared according to the best components and preparing condition.Stability of two sorts of RIF eye drops and solutions of RIF injections diluted by 0.5% glucose injection,0.9%sodium chloride injection respectively were evaluating by stress testing、accelerated testing and long-term test.The results showed that solutions of RIF injections were more stable than RIF eye drops.Provide references for improving the prescription of eye drops. The stability of accelerated testing showed that RIF injections were stable,well quality-controlled and met the purpose and requirement of dosage form design.