Development of an optimized febuxostat self-nanoemulsified loaded transdermal film: in-vitro, ex-vivo and in-vivo evaluation

Febuxostat (FBX) is used to treat gout and chronic hyperuricemia. However, its bioavailability is moderate (49%) as a result of low solubility and first-pass metabolism. Therefore, the aim of our study is to improve FBX bioavailability by enhancement its solubility using self-nanoemulsifying drug delivery system (SNEDDS) technique in the form of transdermal film to avoid hepatic metabolism. To accomplish this goal, Eight SNEDDS formulae were prepared according to a three-factor, two-level D-Optimal mixture design to evaluate the effect of different ratios of the Lemon oil (X1), the surfactant Tween-20 (X2), and the co-surfactant PEG-400 (X3) on the globule size in order to reach smallest globular size. Results revealed that SNEDDS globule size ranged from 177 to 454 nm. The optimized formula consisted of 20% oil, 40% surfactant and 40% co-surfactant. Diffusion study showed improved enhancement in skin permeation that was confirmed by imaging using fluorescence microscope. In vivo plasma data showed significant (p

非布司他（Febuxostat，FBX）临床用于治疗痛风及慢性高尿酸血症。但因其溶解度较低且存在首过代谢，生物利用度仅为中等水平（49%）。本研究旨在通过自纳米乳化给药系统（self-nanoemulsifying drug delivery system，SNEDDS）技术制备透皮膜制剂，以提高非布司他的溶解度，进而改善其生物利用度，同时避免肝脏首过代谢。为达成该研究目标，本研究采用三因素两水平D最优混料设计，制备了8组自纳米乳化给药系统处方，考察柠檬油（X₁）、表面活性剂吐温-20（X₂）与助表面活性剂PEG-400（X₃）的不同配比对制剂粒径的影响，以获取最小粒径的最优处方。研究结果显示，自纳米乳化给药系统的粒径范围为177~454 nm。最优处方的组成为：油相占比20%、表面活性剂占比40%、助表面活性剂占比40%。透皮扩散实验结果表明，制剂的皮肤渗透性能得到显著提升，该结果通过荧光显微镜成像得到验证。体内血浆数据显示，差异具有统计学意义（p