Preparation and quality evaluation of enrofloxacin nanoemulsion

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Enrofloxacin is the first fluoroquinolone antimicrobial agent solely for veterinary use.The drug has a broad spectrum of activity,being active against both Gram-positive,Gram-negative bacteria and mycoplasmas.Now the traditional clinical dosage forms include powder,injection,solution and suspension,and so on.Some new dosage forms such as nanoparticles,microsphere,liposomes,β-cyclodextrin inclusion complex,sustained-release granules,microencapsulation and microcapsules have been also studied and reported accompanying with the development of the new preparation technique,but the research about enrofloxacin nanoemulsion has not yet been reported.The low water solubility is still an important limiting factor hampering enrofloxacin administration and the development of the novel preparation.So,we aimed to prepare enrofloxacin nanoemulsion with enrofloxacin as a model drug and nanoemulsion as a drug carrier by incorporating enrofloxacin into a nanoemulsion to improve its water solubility.In order to screen an optimal prescription for preparing enrofloxacin nanoemulsion,the oil phase was screened among isopropyl myristate(IPM),acetic ether,soybean oil and peanut oil;the surfactant was screened among polyoxyl 40 hydrogenated castor oil,polyoxyethylene castor oil(EL-40),Tween-80,lecithin and Span 80;the cosurfactant was screened among ethanol,1,2-propanediol,glycerin,acetic acid(HAc),lactic acid and propanoic acid;and the mass ratio(Km) of surfactant to cosurfactant was screened among 3∶1,3∶2 and 3∶3,respectively.A pseudo-ternary phase diagram was established to investigate the effect of various compositions on the formation region of the nanoemulsion.The phase diagram was obtained by an aqueous titration method with one axis representing the mixture of surfactant and cosurfactant named as combined surfactant(Smix),another representing the oil phase,and the third representing the water phase.Based on the nanoemulsion region,the optimal prescription was screened.Then,enrofloxacin nanoemulsion was prepared according to the screened prescription and its quality was evaluated.The results showed that the optimized formulation was IPM as oil phase(Table 1),EL-40 as surfactant(Fig.1B),HAc as cosurfactant(Fig.2A),the distilled water as the aqueous phase.In this screened prescription,Km was 3∶2(Fig.3B),and it contained enrofloxacin of 15 %,IPM of 3 %,Smix of 48 %,and distilled water of 34 %.According to the prescription,the prepared enrofloxacin nanoemulsion was with a transparent and uniform appearance,the structural type of oil-in-water,and the spherical droplet observed by transmission electron microscope(Fig.4).The mean size of the nanoemulsion droplet was(22.45 ± 2.92) nm with Gaussian distribution verified by laser scattering analyzer(Fig.5),and the value of pH was 4.63,and the minimal inhibitory concentration(MIC) against Escherichia coli ATCC25922 and Staphylococcus aureus ATCC25923 was both 1/2 times the MIC of the crude drug(Table 2).The nanoemulsion was not found the phenomenon of the delamination,demulsification and medicine leakage under the centrifugalization trial and the thermal test.The results above suggest that the optimal preparation procedure of enrofloxacin nanoemulsion is simple and practicable.Enrofloxacin nanoemulsion has a high solubility,strong antibacterial activity,good stability and benefit administration of group drinking water,and effectually overcome the defects such as a poor water-solubility and instability to preserve the traditional dosage form of enrofloxacin.It can be used as a new type of nano-antimicrobial drug for veterinary clinic.