Research And Development On The Rifaximin Baginal Suppository And Rifaximin Sustained-Release Baginal Effervescent Tablets

As a rifamycin derivative antibiotics,rifaximin is a broad spectrum that is effective against many Gram-positive and Gram-negative organisms,with good antimicrobial activity against a broad spectrum of bacterial species.In2004,rifaxmin was approved by the SFDA in our clinical application. Rifaximin for suspension was licensed by EU and FDA for preventing the endometritis.Based on the full investigation of the subject in the vaginal drogs, Rifaximin vaginal suppository and Rifaximin sustained-release vaginal effervescent tablets had been manufactured preventing the endometritis.The evaluation studies, the stability study and the localized stimulus studies on the two kind of preparations had been studied in this paper.1.Preformulation studyA method for determination of rifaximin by HPLC was established.The HPLC system consisted of C18column(250mm×4.6mm,μm), the mobile phase of water-methanol-acetonitrile (volume ratio15:50:35),UV the detection wavelength was240nm,injection volume was10μl,the flow rate was0.8ml/min,column temperature was30℃. The calibration curve was linear in the range of20μg/ml～40μg/ml,regression formula were obtained through determination with HPLC method: A=40.619C+6.1717,R2=0.9999.The RSD of the variation coefficient was0.61%with a run or0.21%between runs,respectively.The RSD of repetition rate was0.23%、0.2%^0.94%,respectively. Therecovery of the suppository and taballa was good.The results showed that the method was simple,rapid,accurate and suitable for the content determination of the rifaximin vaginal suppository and the rifaximin sustained-release vaginal effervescent tablets.A method for dissolution of the rifaximin sustained-release vaginal effervescent tablets was established.The ultraviolet spectrophotometry consisted of232nm wave-length.The release medium adopted0.1mol/L acid solution containing0.15%SDS and the rate of rotation selected100r/min. The calibration curve was linear in the range of2μg/ml～12μg/ml:A=0.0586C+0.0118,R2=0.9992.The RSD of the variation coefficient was0.14%.The RSD of stability rate was0.19%. The recovery of the taballa was good. The results showed that the method was simple,rapid,accurate and suitable for the dissolution of the rifaximin sustained-release vaginal effervescent tablets.The result of the influence of excipients on rifaximin the differential thermal analysis method was none of Influence between accessories and remedium cardinale.Neithor physics change nor chemical change had happened beween them.2. Research and development on the rifaximin vaginal suppositoryBased on thermostability and the time limit to melt,the prescription and techonlogy of the rifaximin vaginal suppository had been definited. Groundsubstance were formed by constituents(glycerine,60g;powdered gelatine,20g;water,10g;PEG-E,5g;PEG-F,5g).Rifaximin vaginal suppository was prepared by the method of hot melting. First,gelatin was moltened in40degrees C water bath,and then mixed with glycerine. Polyethylene glycol was moltened in80degrees C water bath.Second,the alcoholic solution of rifaximin had been dropped into the polyethylene glycol. At last,the glycogelatin and the polyethylene glycol had been mixed to produce the suppository.All the results of evaluation study (characteristics,average weight variation,ime limit of thawing,he microbial limit, content,and so on) accorded to the Pharmacopoeia.3. Research and development on the rifaximin sustained-release vaginal effervescent tabletsBased on the expanding foam and the dissolution,the prescription and techonlogy of the rifaximin sustained-release vaginal effervescent tablets had been definited. Besides rifaximin as the principal agent, the prescription consisted of Sodium Bicarbonate,acid M,polyethylene glycol, P and K.Mixing the ingredient according to proportion,then tabletting with acid base respectively by the wet granulation. Medicine had been crossed the sieve of six before size reduction.Then soft wood had been made by the mixing medicine. Plletization was made by the sieve of tween-four and put into4degrees C for two and a half hours.At last, tablets had been definited after mending pill and mixing.All the results of evaluation study (characteristics,average weight variation,the friability,the microbial limit,the dissolution, content,and so on) accorded to the Pharmacopoeia.4.The stability study and localized stimulus study on praeparatum Three groups of the rifaximin vaginal suppository and the rifaximin sustained-release vaginal effervescent tablets had been preparated by the quality standard of the Pharmacopoeia which had been put in the temperature of30℃±2℃and the relative humidity of65%±5%since six months. In the period of timeaccelerated rest,all of the results of the two praeparatums accorded to the Pharmacopoeia.Through the observation of physiological activity, clinical pathology and histopathology after administer the rabbits, judge the irritative responses on vagina about this two kind of praeparatum.The result showed that local application on vagina about this two kind of praeparatum had no stimulation and security.