The Preparation And Quality Investigate Of Miconazole Nitrate Thermosensitive Vaginal Gel

Miconazole Nitrate(MN) is an imidazole antifungal agent, commonly used to treat fungal infections. It is also an therapeutic agent that can be used for treatment of vaginal candidiasis(VC).There are several vaginal formulations contained Miconazole Nitrate,such as tablets,creams,capsules,suppositories,however,they have some limitations:leakage,messiness,leading to short time of retention and distribution.Finally,a novel vaginal dosage form has been designed and developed which can meet these requirements,the new formulation is thermosensitive vaginal gel.In preformulation firstly investigated excipients properties of moisture absorption, in addition,the compatibilities have been researched between Miconazole Nitrate and excipients.meanwhile, high performance liquid chromatography was applied to studies of the physicochemical properties of inpurity,contents,and so on.In order to select desirable formulation,the solution of sedimentation rate and adhesion and stability have been measured.we found that when poloxamer407mixed with hydroxypropylmethylcellulose(HPMC),the viscosity of HPMC was reduced or disappeared; sodium alginate have a good compatibility,but Miconazole Nitrate was easily deposited,as the suspension liquid contained sodium alginate was placed at low-temperature environment or at room temperature for a long period of time.Finally,the better prescription was composition of1.9%sodium carboxymethyl cellulose800-1200(CMC-Na800-1200),16.8%poloxamer407,5%poloxamer188,5%glycerol,4%Miconazole Nitrate,water.meanwhile,the process of preparation of gel had been studied.it showed that suspending agent and poloxamer should separately swell, as to get rid of the surface water film,drug had to premix with liquid of poloxamer,and then mixed with solution of suspension agent.this process can ensure the stability of suspension and no small bubbles in the solution.We did some experiments to evaluate the sample,such as traits,centrifugal experiment,adhesion,sedimentation ratio,contents,release profils,etc,and then standard of quality of gel had been established.The pharmacopoeias referenced to the methods of analysis of MN were similar between the china and the united states over the world.The phase of HPLC used to determine the contents was:methanol:acetonitrile:1.5%ammonium acetate=40:40:20;and the phase of substances were:methanol: acetonitrile:1.5%ammonium acetate=40:35:25.Franz pool that FDA recommended and basket method were not adopted to evaluate the drug release,because their volumes were too small,finally,the improvement paddle method had been applied.Due to the formulation and methods were different with FDA,the concentration of dissolution medium contained SDS had been increase. The result of release profile of the in stiu gel showed that it had good sustained release compare to other vaginal dosage forms which contained MN.The stability of the gel had been studied,found that alkali and oxidation could increase impurities,it is valuable for packaging and storage of the prodct.