Studies On Bifonazole And Ketoprofen Emulgels

An antifungal drug bifonazole（BFZ）and an NSAID ketoprofen（KP）were taken as model drugs to prepare two oil-in-water emulgels.The aim was to enhance the retention content in the skin for the former drug,and to improve the permeation across the skin for the latter drug.The procedure was to prepare oil-in-water emulsions firstly which then were dispersed into carbomer940 containing base.HPLC methods were applied to determine the concentration of BFZ and KP emulgels in vitro. Based on the requirement of the intrinsic properties,dosage forms and the preparation of drugs, some necessary tests were chosen.These tests were the determination of the solubility of two drugs in different kinds of solvents,oils and suffactants and the apparent partition coefficients of two drugs in octanol/distilled water.The results indicated that BFZ was a highly lipophilic compound, and was more easily soluble in oleic acid.The solubility of KP was dependent on pH values, increasing along with the increase of pH values,but its logP presented converse changes.The solubility of KP in oils was commonly less than that in surfactants.The emulgel containing 1%BFZ was prepared.The Single factor test was used to choose the kind of oil and emulsifier.The stability after centrifuging or in 40℃were taken as the evaluation standard to optimize the amount of the oil and emulsifier in the formulation.The final formulation contained 5%oleic acid as an oil phase and 2.5%Tween80 as an emulsifier.Other ingredients and the preparation including gel bases,antioxidants and preservatives were also investigated.And then we obtained the best formulation and preparation of BFZ emulgel.The permeation across the rat skin and skin retention content determination method were established to analyze and compare the permeation characteristics of the BFZ emulgel and other two commercially available products BFZ gel and cream.The results showed that the prepared emulgel was glossy,unoily as well as extremely easy to spread and clear with some advantages of emulsions and gels.The permeability of drug across the excised rat skin from three preparations were poor;The steady state flux J_s were 0.56μg·cm^-2·h^-1,0.37μg·cm^-2·h^-1,0.18μg·cm^-2·h^-1respectively.The retention content in rat skin of three preparations were 124.13+23.47μg·g^-1,34.14±14.54μg·g^-1,71.36±28.77μg·g^-1.The retention content in rat skin of the emulgel was obviously greater than that of commercially available preparations including cream（P＜0.01）and gel（P＜0.05）.It is advantageous for the therapy of the skin diseases.The same methods were adopted to select the ingredients of KP emulgel.The final formulation of KP emulgel contained 10%ethyl oleate as oil phase and 5%Tween80 as emulsifier.HPLC method was harnessed to determine the vitro permeation of KP across the excised rat skin in the presence of several penetration enhancers and to investigate their enhance effects.These enhancers including Azone,menthol,oleic acid,diethylene glycol monoethyl ether（Transcutol）,and N-methyl-pyrrolidone（NMP）were used alone or collaboratively.The other factors which had an effect on the permeation of KP across the excised rat skin from the emulgel were also investigated. These factors included different amount of drug,different amount of carbomer940,and different pH of emulgel.The results showed NMP had an obvious enhance effect,ER reached 2.64（P＜0.05） when 6%NMP was added.Different amount of drug or carbomer940 in the emulgel influenced the permeation of KP across the excised rat skin to some extent;Different pH.of the emulgel had no significant impact on the permeation of KP.The permeation of KP across the excised rat skin from emulgel and commercially available products gel were compared.Q_12hwere 1167.22±203.16μg·cm^-2and 908.1±183.5μg·cm^-2respectively.The steady state flux J_s were 124.97μg·cm^-2·h^-1and 94.06μg·cm^-2·h^-1individually.ER was 1.33.The permeation increased to some degree,although the change was not significant（P＞0.05）.The quality study,which included trait,identification,pH,content determination,the permeation of KP across the excised rat skin from the emulgel were performed.And the preliminary stability tests and the skin irritation test were also done.The influencing factors included low and high temperature,illumination,centrifugalization and ambient temperature.The results revealed that the quality of two emulgels met the requirments.BFZ emulgel was stable but KP emulgel was not stable when exposed to the strong light which indicated it should be protected from light.The skin irritation test showed no skin irritation of the two emulgels.