Studies On Preparation And Efficacy Of Ciclopirox Olamine Nanoemulsion

Objective: Ciclopirox olamine is broad-spectrum antifungal drug and has stronginhibitory effect to skin pathogens. Due to its low bioavailability and poor solubility in waterthis study developed the ciclopirox olamine nanoemulsion (CPX-NE) as a novel transdermaldrug for clinic application.Methods:(1) Preparation and quality evaluation of CPX-NE: The optimum oil phasewas selected by its soluble ability to ciclopirox olamine and the optimum surfactant wasdetermined by the area of pseudoternary phase diagrams. The structure pattern of CPX-NEwas identified by staining. In addition, shape and properties of CPX-NE were investigated bytransmission electron microscope, Zetasizer Nano ZS instrument and UV-spectrophotometer.(2) Stability evaluation of CPX-NE: The stability of CPX-NE was evaluated by temperaturetest, photostability test, accelerated test and long-term test under different test condition.Meanwhile the period of validity of CPX-NE was determined by long-term test.(3) Safetyinvestigation of CPX-NE: The skin acute toxicity, skin irritation and skin sensitization wereevaluated by administering CPX-NE, blank-NE and physiological saline to the hairless skinof test animals.(4) Transdermal property evaluation of the CPX-NE: Transdermal propertywas evaluated by improved Franz diffusiing cells method.(5) Antifungal activity evaluation:Antifungal activity test of ciclopirox olamine in vitro was conducted by using the microdilutionmethod.Results:(1) Results of preparation and quality evalution of CPX-NE. It can form astable ciclopirox olamine nanoemulsion, at room temperature, in the presence of isopropylacetate as oil, Cremorphor RH40as surfactant, ethanol as cosurfactant. At the same time,mass ratio Kmof surfactant and cosurfactant equals3:2. The proportion of various parts wasisopropyl acetate4.50, Cremorphor RH4024.48, ethanol13.83and distilled water54.43.Nanoemulsion droplets were spherical with a mean diameter of11.4nm, among of which73%were distributed between10nm and20nm, and the polydispersity index (PDI) of0.132.(2)Results of stability evaluation of CPX-NE. By temperature test, photostability test,accelerated test and long-term test it illustrated that nanoemulsion was still transparent,uniform and not stratified as well as its period of validity could be20months.(3) Results ofsafety evaluation of CPX-NE. It showed that CPX nanoemulsion was a nonirritating drug and a weak sensitizer.(4) Results of transdermal property evaluation of CPX-NE. The results oftransdermal permeability of ciclopirox olamine nanoemulsion in vitro test illuminate that thetransdermal rate of ciclopirox olamine nanoemulsion and ones with2%,5%azone was22.381±0.114μg/cm~2·h,134.573±0.012μg/cm~2·h,50.350±0.001μg/cm~2·h respectively,whereas the transdermal rate of ciclopirox with20%ethanol solution was10.891±0.062μg/cm~2·h. It shows that ciclopirox olamine nanoemulsion enhances its percutaneouspenetration (P<0.01) and it can further improve its transdermal ability in vitro when the azonewas added (P<0.01).(5) Results of antifungal activity evaluation of CPX-NE. The results ofantifungal activity test in vitro showed that the MIC of Candida albicans, Saccharomycescerevisiae and Staphylococcus aureus was0.125μg/ml,0.25μg/ml and16μg/ml respectively,which was better than results of ciclopirox olamine solution and bifonazole solution obviously.It is manifest that nanoemulsion as a kind of drug carrier can improve the antifungal activityof ciclopirox olamine.Conclusion: The oil-in-water CPX-NE could be diluted by water unliminatedly and wastransparent. The CPX-NE prepared in this research satisfied the requirement of nanoemulsionformulation and had fine stability, safety and efficacy.