Preparation,Quality Standard,Stability,safety Research Of Metronidazole,Clotrimazole And Chlorhexidine Acetate Vaginal Cream

ObjectiveCream prescription and main process parameters were optimized by the orthogonal design method.Metronidazole,clotrimazole and chlorhexidine acetate vaginal cream was prepared.Quality research of the cream was made to determine the quality standards.We studied the stability research of Metronidazole,clotrimazole and chlorhexidine acetate vaginal cream,including test of influence factors,stability tests of 6 months' accelerating experiment and 12 months' long-term studies.Safety research of the cream was investigated,including test of vaginal irritation and skin allergic reaction.MethodsWith the amounts of tween 80,liquid paraffin,stearic acid,monostearate and the emulsifying temperature,additional method of principal agents and emulsifier,emulsifying time,mixing speed as the research objects.With the appearance of cream,smoothness,spreadable and stability as indicators,cream prescription and main process parameters were optimized by the orthogonal design method.We conducted the quality standard research of the cream according to the applicable quality requirements.The main indexes were character,identification,packing volumes,uniformity,related substances,contents and so on.We established a systematic testing standards to control the quality of the final products,and the stability of the samples were investigated.We also study safety research of the cream.With the rabbits as experimental objects,vaginal irritation reaction was studied.With the mice as experimental objects,skin allergic reaction was studied.ResultsThrough the orthogonal design tests,we got the best prescription,for tween 80 was 0.4g,liquid paraffin was 0.4g,stearic acid was 1.0g,monostearate was 1.0g.We also got the best preparation technology,the cream was obtained by mixing the aqueous phase containing metronidazole,chlorhexidine acetate,tween 80 and the oil phase containing clotrimazole at 65?,the stirring time was 20 min,the stirring speed was 200 r·min-1.Then according to the best prescription,three batches of metronidazole,clotrimazole and chlorhexidine acetate vaginal cream were prepared,the cream samples were centrifuged in 6000 r·min-1 for 20 min,placed at 55? in the incubator for 6 h,placed at-20? in the refrigerator for 24 h respectively,3 batches of the cream had no obvious changes in appearance.We determined the contents of the cream by HPLC,the regression equation of metronidazole,clotrimazole,chlorhexidine acetate were A1= 5316.6C + 34149,linear range was 100-800?g/m L(R= 0.9998),A2 = 824.44 C + 33568,linear range was 80-640?g/m L(R= 0.9998),A3 = 15609C-21992,linear range was 4-32?g/m L(R= 0.9998)respectively.The recoveries of the cream were 100.26%,99.53%,99.74% respectively.The principal contents of 3 batches of cream samples were in accordance with the provisions.The method is specific,precise and is suitable to determine principal agents of the cream.The stability study showed that the product all complied with the prescribed standards.Safety research showed that the cream had no vaginal irritation and skin allergic reaction.The result stated that the cream was cautious as topical agents.ConclusionsUtilising the orthogonal design method,we optimized cream prescription and main process parameters,metronidazole,clotrimazole and chlorhexidine acetate vaginal cream was ready successfully.The cream had uniform color and suitable viscosity and appropriate ductility.The quality standard was scientific,reasonable and feasible.Stability of homemade samples was conformed to the required standards.The cream had no vaginal irritation and skin allergic reaction.It is benign in clinical application.