Studies On Preparation And Efficacy Of Compound Terbinafine Nanoemulsion

Objective: To develop a compound terbinafine nanoemulsion, and studied the stability,safety and availability of the compound terbinafine nanoemulsion.Methods:（1） The formula of the compound terbinafine nanoemulsion was determinedby pseudoternary phase diagrams. And the structure type, appearance and particle diameterdistribution were measured by sudan red and methylene blue staining, transmission electronmicroscope and laser particle size analysator respectively. The compatibility of theconstituents of compound terbinafine nanoemulsion was measured by High PerformanceLiquid Chromatography （HPLC）.（2） Accelerated test, long-term test and photostability testwere applied to observe the stability of the compound terbinafine nanoemulsion.（3）Analytical methods were established by HPLC to determinate the contents of terbinafine,eugenol and erythromycin in the compound terbinafine nanoemulsion.（4） Skin irritation test,acute dermal toxicity test and dermal sensitization test were used to evaluate the safety of thecompound terbinafine nanoemulsion.（5） The transdermal property of the compoundterbinafine nanoemulsion was evaluated by improved Franz diffusiing cells method.（6） Theefficacy of the compound terbinafine nanoemulsion was investigated by bacteriostatic test andacaricidal experiment in vitro, and clinical trial.Results:（1） The optimum prescription of the compound terbinafine nanoemulsion was w（terbinafine）=1.3%, w （eugenol）=2.5%, w （erythromycin）=1.3%, w （Tween-80）=24%,w （ethanol）=12%, w （IPM）=2%, w （distilled water）=56.9%. The type of the compoundterbinafine nanoemulsion was oil-in-water and the liquid was yellow, transparent andhomogeneous. The nanoemulsion drop presented as spherical shape at the average drop sizeof11.9nm with a polydispersity index of0.06, and about95.3%of the drop sizes weresmaller than20nm. And terbinafine, eugenol and erythromycin were compatible in thecompound terbinafine nanoemulsion.（2） Result of the accelerated test, after6months thecontents of the drugs in the compound terbinafine nanoemulsion were not significantlydifferent with the control. But the relative contents were slightly reduced, and the period ofvalidity was19months. The compound terbinafine nanoemulsion should keep without light asthe result of the photostability test.（3） In the compound terbinafine nanoemulsion, they werelinear when terbinafine in the range of10³0μg·mL^-1, eugenol in the range of20¹00 μg·mL^-1, and erythromycin in the range of2.4⁶.4μg·mL^-1, and the average recovery ratewere98.80%,98.48%, and98.90%, respectively, and the RSD of the with-in-day precisionof terbinafine, eugenol and erythromycin were2.00%,1.38%, and1.12%, the RSD of theday-to-tay precision were2.13%,1.92%, and1.67%, respectively.（4） In the acute dermaltoxicity test, the weight of the compound terbinafine nanoemulsion treated rabbits were nodifferent with the controls, and the dermal irritant test showed the compound terbinafinenanoemulsion was a nonirritating drug and a weak sensitizer.（5） The transdermal rate ofterbinafine and eugenol by the compound terbinafine nanoemulsion was0.8403μg cm^-2 h^-1and0.3362μg cm^-2 h^-1, with0.2668μg cm^-2 h^-1and0.1566μg cm^-2 h^-1by the mixedsuspension, respectively.（6） In the in vitro test of pesticide effectiveness, the minimalinhibitory concentration and minimum bactericidal concentration were significantly lowerthan the mixed suspension or erythromycin enteric-coated tablets （P<0.01）. And in the in vitroacaricidal test, the death rate by the compound terbinafine nanoemulsion was significantlyhigher than pyridaben solution （P<0.05）. The clinical efficacy test showed that the effectiverate and the cure rate of the compound terbinafine nanoemulsion were significant higher thanivermectin （P<0.05）.Conclusion: The compound terbinafine nanoemulsion prepared in this research satisfiedthe requirement of nanoemulsion formulation and had fine stability, safety and efficacy.