Preparation Of Sulconazole-loaded Nanoemulsions And Its Transdermal Administration Studies

Sulconazol(SCZ)is a new broad-spectrum antifungal agent,which has good antifungal effect on Canidia albicans,Trichophyton rubrum and Trichophyta,etc.It is clinically used for the treatment of tinea corporis,tinea cruris,tinea pedis and tinea versicolor.The current dosage form of SCZ has been marketed as a spray.However,due to the poor water-solubility of SCZ,the current dosage forms have some disadvantages,such as low bioavailability,short retention time of SCZ in skin lesions,and unsatisfactory effect.Therefore,it is of great scientific significance and practical value to develop a new dosage form according to the physical and chemical characteristics of the drug to improve its bioavailability and clinical effect.In this study,a method for the determination of Sulconazole was established,and then the nanoemulsion(NEs)was selected as a new delivery carrier to prepare Sulconazole-loaded nanoemulsions(SCZ-NEs).The formulation was optimized and the in vitro properties of nanoemulsion were characterized.The particle size,polydispersity index(PDI)and Zeta potential of SCZ-NEs were measured.The morphology and micromorphology of SCZ-NEs were observed by Transmission electron microscopy(TEM).Drug loading(DL)% and Encapsulation efficiency(EE)% of SCZ-NEs were measured,and its stability was investigated.The permeation rate and cumulative penetration were used to evaluate the transdermal properties in vitro.The antifungal effects on different fungi were investigated by bacteriostatic circle experiment.The first part of this study is the establishment of HPLC method for the determination of sulconazole.The detection wavelength was determined by full wavelength UV scanning,and the effects of different mobile phase ratios on the elution capacity,peak shape and retention time of sulconazole were investigated.The results of the methodological study showed that sulconazole had a good linear relationship in the concentration range of 1.0-16.0 ?g/m L,and its specificity,stability,precision and recovery all met the requirements of the methodological study.The second part of this study is the preparation and characterization of SCZ-NEs in vitro.The ratio of surfactant to co-surfactant(Km)in SCZ-NEs formulation was screened by pseudo ternary phase diagram method,the ratio of oil phase and mixed surfactant and the ratio of water phase were investigated,and the formulation of SCZ-NEs was optimized by central composite design-response surface methodology(CCD-RSM).The particle size,PDI and Zeta potential of the SCZ-NEs prepared by the optimized formulation were measured.The appearance and micro morphology of SCZ-NEs were observed by transmission electron microscopy,and DL% and EE% of SCZ-NEs were measured.The prepared SCZ-NEs were placed at room temperature for 14 days,and the particle size,PDI,Zeta potential,DL% and EE% were measured by the above methods on days 0,7 and 14,respectively.The stability of SCZ-NEs was evaluated by centrifugation at 10,000 rpm for 30 min after 14 days.The results showed that SCZ-NEs was easier to emulsify and more stable when the Km ratio was 2:1.The proportion of sulconazole,Capryol 90,labrasol,1,2-propylene glycol and aqueous phase in the optimized SCZ-NEs prescription were 0.5 %,5.4 %,28.9 %,14.4 % and 50.8 %,respectively.SCZ-NEs was prepared by drop addition method.The optimized SCZ-NEs particle size distribution was narrow and uniform,with particle size of 52.3 ± 3.8 nm,PDI of 0.205 ± 0.02,Zeta potential of 23.3 ± 1.2 m V,DL% of 0.47 ± 0.05 % and EE% of 87.1 ± 3.2 %.The appearance of the SCZ-NEs prepared by TEM observation was a spherical-like polydisperse emulsion with uniform size,and the particle surface was covered by a thin layer of surfactant.The prepared SCZ-NEs was placed at room temperature for 14 days,and its physical and chemical properties did not change significantly,showing a transparent appearance all the time.After centrifugation,there was no turbidity,no drug precipitation,and it had good stability at room temperature.The third part of this study investigated the transdermal absorption behavior of SCZ-NEs in vitro.The transdermal properties of SCZ-NEs and SCZ solution was investigated in vitro with miconazole(MCZ)cream as the control drug.The results showed that the penetration rate of SCZ-NEs was 1.76 times that of MCZ cream and 2.98 times that of SCZ solution.The cumulative permeability of SCZ-NEs within 12 h was significantly higher than that of MCZ cream(P < 0.05)and SCZ solution(P < 0.01).In the fourth part of this study,the antifungal effect of SCZ-NEs in vitro was investigated by using the bacteriostatic circle test(ZOI)AGAR drilling method.Candida albicans and Trichophyton rubrum were used as the experimental strains,,respectively,to evaluate the antifungal effect of SCZ-NEs on the two fungi by comparing the inhibitory circle diameters of blank NEs(group A),SCZ-NES(group B),MCZ cream(group C)and SCZ solution(group D).The ZOIs of Candida albicans were 23.5 ± 2.4,17.0 ± 2.2 and 12.5 ± 1.9 mm in Group B,C,D after 48 hours treatment,while those of Trichophyton rubrum were 20.4 ± 2.5,16.8 ± 2.2 and 13.5 ± 1.2 mm in Group B,C and D after 48 hours treatment.The antifungal effect of SCZ-NEs on Candida albicans was significantly greater than that of MCZ cream(P < 0.05)and SCZ solution(P < 0.01),and the antifungal effect on Trichophyton rubrum was significantly greater than that of SCZ solution(P < 0.05).The results of this study indicate that the preparation of SCZ into NEs can improve the stability and skin permeability of the drug.It has obvious advantages in increasing drug load and improving antifungal effect.The results of in vitro experiments showed that the antifungal activity of SCZ contained in NEs was significantly improved.Therefore,SCZ-NEs is expected to provide a new effective preparation for clinical antifungal therapy.