Preparation Of Fluconazole Cubic Phase Gels And Its Efficacy Evaluation

Objective:Fluconazole(FLZ) was chosen as model drug and preparations of fluconazole cubic phase gels and constructs a murine model of vaginal candidiasis to observe the therapeutical effect of fluconazole cubic phase gels on candidal vaginitis. This study explores the new therapy drug for candida vaginitis and provides a new choice for the treatment of the monilial vaginitis in clinical treatment.Methods:The first part is for fluconazole cubic phase gels prescription technology research,through the ternary phase diagram selection and preparation process of groping,finding out the best area of fluconazole cubic phase gels.The second part is fluconazole cubic phase gels quality control. Glyceryl monooleate(GMO) was used as the liquid crystal material to prepare the fluconazole loaded cubic phase gels. Polarizing light microscope(PLM) and small angle X-ray scatting(SAXS) were used to confirm the internal structures and establish HPLC method for determination of their content.At the same time establish for the preparation of fluconazole cubic phase gels material related substance examination.The third part is preliminary stability test. According to the “Chinese pharmacopoeia”mainly carry out the influence factor test,acceleration test and long-term test.The fourth part is Fluconazole cubic phase gels preliminary pharmacodynamics research:1.Construct a mice model of Candidal Vaginitis;2.To investigate the different doses of fluconazole cubic phase gels in the therapeutic action of candida vaginitis of mice.Results:1.The result of prescription technology research:In ternary phase diagram of the2.optimal area for the preparation of the vaginal with fluconazole cubic phase gels.Prescription area for GMO:anhydrous ethanol:water = 45%:5%:50% to 80%:0:20%,prepared by injection method.3.The result of quality control:(1)Cubic phase gels were the dark field under PLM,SAXS showed that the blank cubic phase gels had two single peaks:q1(0.83209nm-1) and q2(1.017nm-1) while the fluconazole-loaded cubic phase gels had two single peaks:q1(0.81888nm-1) and q2(0.95095nm-1).(2)Establish HPLC method for fluconazole cubic phase gels to proceed content determination,the linearity within the range of 20-500μg/ml was good.In establishing the chromatographic conditions,related substances were completely separated from FLZ and the detection limit was 0.4μg,theory pedal number is 7787.219.It was found that the fluconazole cubic phase gels preparation on the acid、 alkali、 heat、 light、oxidation damage under the condition of product all can and effective separation of main component, the solvent blank produced by the chromatographic peak does not interfere with the determination, shows that the method has good specificity.3.The experimental result of preliminary stability:Preparative Fluconazole cubic phase gels doing preliminary stability test,Results show that the gels at high temperature(40℃), high humidity under the condition of stability is good, the light is not stable(need to avoid light preservation), in the long term stability conditions and the constant temperature acceleration condition are stable.4.The experimental result of preliminary pharmacodynamics:(1)Using kunming rats as experimental animals and build candida albicans vaginitis model:after building the model two days, smear microscopic examination of the fungus can be found a small amount of spores and pseudohyphae.On the fourth day, smear microscopic examination of the fungus finds a large number of pseudohyphae and spores sprout.Histopathologic slice vaginal mucous membrane surface a large number of hyphae and spores.(2)Fluconazole cubic phase gels of the therapeutic action test on the vaginal candidiasis :after treated for seven days in a row,on the second day、the fifth day、the tenth day respectively collected the mouse vaginal lavage colony and conduct fungus counting.When we used the SPSS 17.0 software analysis and found that different doses of fluconazole cubic phase gels can reduce mouse vaginal lavage colony count,comparing with model group had significant difference(P<0.05).At the same time,through the organization pathological findings: in the given medicine group there were only a small amount of inflammatory cell infiltration(HE dyeing), vaginal mucosa not seen hyphae, a small amount of spores(PAS dyeing);model group showed a large number of spores、hyphae and proliferation(PAS dyeing).Conclusion:1.This experiment adopted the ternary phase diagram to filter the prescription of fluconazole cubic phase gels,which they have clarify,transparent appearance.2.PLM and SAXS are reliable for characteriazation of cubic phase gels.The HPLC method can be used for FLZ cubic phase gels about quality control and related substances examination.3.Preliminary stability studies find that under the dark condition, the FLZ cubic phase gels stable is well.4.Pharmacodynamics experiment found that fluconazole cubic phase gels can inhibit mice candida albicans growth of hyphae and spores proliferation, it has certain therapeutic effect for treatment of vaginal yeast infection, to a certain dose, with the increase of drug concentration, the treatment effect increased.Fluconazole cubic phase gels could be developed for new type of vaginal drug delivery preparation.