Studies On Preparation And Efficacy Of Itraconazole Nanoemulsion

Objective: Iraconazole is a kind of broad-spectrum antifungal drug, but it comes with itsown disadvantages, such as poor solubility in water, lack of existing preparation and so on.We prepared iraconazole nanoemulsion, a kind of new drug delivery system, to improvethese disadvantages and provided a new, safe and efficient percutaneous delivery system totreat skin fungai infection at the same time.Methods:(1) Prescription screening and preparation of iraconazole nanoemulsion: Theappropriate oil phase was selected by its solubility to iraconazole.The optimum surfactant andKm were determined by the area of pseudoternary phase diagrams, then the iraconazolenanoemulsion was prepared by adding water into oil phase which was called phasetransformation.(2) Quality evaluation of iraconazole nanoemulsion: staining was used toidentify the structure pattern of iraconazole nanoemulsion, and its shape and distribution ofiraconazole nanoemulsion droplets were studied by transmission electron microscope.Zetasizer Nano ZS instrument was used to study its particle distribution, the average particlesize and polydispersity index. The stability of iraconazole nanoemulsion was evaluated bydifferent methods including temperature, accelerated and exposure test.(3) Safety evaluationof iraconazole nanoemulsion: Safty of iraconazole nanoemulsion was evaluated by skin acutetoxicity and irritation test.The skin acute toxicity test was conducted with the help of rat skin.The skin irritation test divided into two parts was evaluated with the aid of rabbit skin.(4) Thetransdermal absorption of iraconazole nanoemulsion: The transdermal performance wasconducted with the modified Franz diffusion cell and in vitro mice abdominal skin whosespecific parameters were permeation volume and transdermal retention volume.(5) Inhibitoryeffect of iraconazole nanoemulsion: The minimal inhibitory concentrations (MIC) ofiraconazole nanoemulsion against Candida albicans, Sacchaaromyces and Trichophytonrubrum were determined in vitro antifungal tests to evaluate its activities.Results:(1) Results of prescription screening and preparation of iraconazolenanoemulsion: The formula of iraconazole nanoemulsion contained24.44%EL-40,4.58%cinnamaldehyde,1.24%iraconazole,4.58%Ethyl Acetate,12.17%isopropyl alcohol and52.99%water. The iraconazole nanoemulsion prepared was transparent light yellow liquid.The droplets of M-NE were spherical and well distributed with the average particle size of 13.9nm and PDI of0.060.(2) Results of quality evaluation of iraconazole nanoemulsion: Thestructure type of iraconazole nanoemulsion was oil-in-water with circular and equallydistributed particles. Its diameter distribution was narrow with the average particle size14.48nm. Its polydispersity index was0.014, pH was5.0±0.2and Zeta potential was（-17.4±0.4）mV. Its quality was stable except under a high temperature. Iraconazole nanoemulsionstill kept original appearance after a high-speed centrifugal and acceleration test.(3) Results ofsafety evaluation of iraconazole nanoemulsion: The rats in skin acute toxicity test behavednormally and no one died，which showed that iraconazole nanoemulsion had little skin acutetoxicity,which belonged to non-toxic. Iraconazole nanoemulsion had no skin irritation tocomplete rabbit skin, but had minor skin irritations to abraded skin however could berecovered in a short time.(4) Results of The transdermal absorption of iraconazolenanoemulsion: The transdermal absorption of iraconazole nanoemulsion was superior toiraconazole solution、 iraconazole nanoemulsion with2%azone and iraconazolenanoemulsion with5%azone. The permeation volumes of these4different drugs were41.10μg·cm-2,38.66μg·cm-2,37.75μg·cm-2,14.31μg·cm-2respectively and transdermal retentionvolumes were8.91±0.14μg·cm-2、0.64±0.10μg·cm-2、3.47±0.30μg·cm-2and3.27±0.66μg·cm-2respectively. So iraconazole nanoemulsion, as a new kind of transdermal drugdelivery system, improved transdermal retention volume at the target site.(5)Results ofinhibitory effect of iraconazole nanoemulsion: The minimal inhibitory concentrations ofiraconazole nanoemulsion against Candida albicans, Sacchaaromyces and Trichophytonrubrum was improved16times,8times and4times respectively compared withKetoconazole Cream.Conclusion: The iraconazole nanoemulsion prepared in this research is clear andtransparent. As a new transdermal drug delivery system, the iraconazole nanoemulsion meetsthe requirement of nanoemulsion formulation and has fine stability, safety and efficacy.