Studies On Preparation And Efficacy Of Compound Naftifine Hydrochloride Nanoemulsion

Objective: To develop a compound Naftifine hydrochloride nanoemulsion, and studied the quality, safety, transdermal quality and availability of the compound Naftifine hydrochloride nanoemulsion. And also offered a new form for Naftifine hydrochloride.Methods:(1) The formula of the compound Naftifine hydrochloride nanoemulsion was determined by pseudo ternary phase diagrams, and the oil was screened by solubility of Naftifine hydrochloride.(2)Quality evaluation of the compound Naftifine hydrochloride nanoemulsion: structure type was identified by staining; shape, particulate radius distribution and polydispersity index was examined by transmission electron microscopy and laser particle size analyzer; high performance liquid chromatograph was used to detect its content; stability was determined by acceleration tests, light stability tests and temperature stability tests.(3)Safety evaluation of the compound Naftifine hydrochloride nanoemulsion: skin acute toxicity test, skin irritation test and skin allergy test was used to evaluate the safety of the compound Naftifine hydrochloride nanoemulsion.(4)Transdermal property of the compound Naftifine hydrochloride nanoemulsion in vitro: improved Franz diffusing cells method was used to evaluate its transdermal property.(5)Bactriostasis of the compound Naftifine hydrochloride nanoemulsion in vitro: microdilution method was used to test minimum inhibitory concentration of bacteria, and compared with drug solutions.(6)Clinical trial of the compound Naftifine hydrochloride nanoemulsion: clinical efficacy was performed on Naftifine hydrochloride nanoemulsion.Results:(1)The formula of the compound Naftifine hydrochloride nanoemulsion: 0.72%Naftifinehydrochloride,3.62%Cinnamaldehyde,16.27%EL-40, 5.42%propylene glycol and 73.97% distilled water respectively;(2)the type of the compound Naftifine hydrochloride nanoemulsion was oil-in-water and it’s liquid was amber, transparent and clear, the drop of nanoemulsion presented spherical in transmission electron microscope, uniform distribution, mean grain size of the drop was13.35 nm, and polydispersity index was 0.196, with good stability and no delamination, flocculation and precipitation. The best determine wavelength of Naftifine hydrochloride and Cinnamaldehyde in the compound Naftifine hydrochloride nanoemulsion was254 nm, 285 nm, with good linear relation in the range of 0.78125~25 μg/m L and 1.5625~50 μg/m L.(3)There were no acute toxicity, obvious irritant, allergic reaction in the compound Naftifine hydrochloride nanoemulsion, so it’s a high safety skin drug.(4)transdermal osmotic rate of Naftifine hydrochloride in the compound Naftifine hydrochloride nanoemulsion and mixed drug solution was5.50397±0.056547μg/cm2.h 、1.88217±0.003707μg/cm2.h, and transdermal osmotic rate of Cinnamaldehyde in the compound Naftifine hydrochloride nanoemulsion and mixed drug solution was174.27667±0.047258μg/cm2.h、57.06700±0.096576μg/cm2.h, that means the transdermal property of compound Naftifine hydrochloride nanoemulsion significant better than mixed drug solution(P<0.01).(5) The results of antifungal activity test in vitro showed the MIC to Microsporum canis、Microsporum gypseum、Trichophyton mentagrophytes and Trichophyton rubrum(0.008, 0.016, 0.008 and 0.016μg/m L, respectively);MBC(0.156, 0.156, 0.039, 0.156μg/m L), which was better than results of Naftifine hydrochloride and Cinnamaldehyde technical mixture. The result showed that the combination of Naftifine hydrochloride and Cinnamaldehyde enhanced the antifungal activity.(6)Result of clinical trial showed the cure rate of compound Naftifine hydrochloride nanoemulsion better than Naftifine Hydrochloride Ointment.Conclusion: The compound Naftifine hydrochloride nanoemulsion prepared in this research satisfied the requirement of nanoemulsion formulation and had fine stability, safety and efficacy.