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基于纳米结构脂质载体的氟比洛芬局部凝胶:设计、表征和体内评价。

Nanostructured lipid carriers (NLC) based topical gel of flurbiprofen: design, characterization and in vivo evaluation.

机构信息

School of Pharmaceutics, Pharmaceutical University of Shenyang, Shenyang 110016, People's Republic of China.

出版信息

Int J Pharm. 2012 Dec 15;439(1-2):349-57. doi: 10.1016/j.ijpharm.2012.08.040. Epub 2012 Sep 15.

Abstract

Nanostructured lipid carriers (NLC)-based gel was developed as potential topical system for flurbiprofen (FP) topical delivery. The characterizations of the prepared semisolid formulation for topical application on skin were assessed by means of particle size distribution, zeta potential analysis, X-ray analysis, in vitro percutaneous penetration, rheological study, skin irritation test, in vivo pharmacodynamic evaluation and in vivo pharmacokinetic study. The NLC remained within the colloidal range and it was uniformly dispersed after suitably gelled by carbopol preparation. It was indicated in vitro permeation studies through rat skin that FP-NLC-gel had a more pronounced permeation profile compared with that of FP-loaded common gel. Pseudoplastic flows with thixotropy were obtained for all NLC-gels after storage at three different temperatures. No oedema and erythema were observed after administration of FP-NLC-gel on the rabbit skin, and the ovalbumin induced rat paw edema could be inhibited by the gel. The maximum concentration in plasma was 29.44 μg/ml and 2.49 μg/ml after oral and topical administration, respectively. While the amount of drug accumulated in skin after topical application was much higher than oral application. In conclusion, NLC-based gel could be a promising vehicle for topical delivery of FP.

摘要

基于纳米结构脂质载体(NLC)的凝胶被开发为一种潜在的局部递药系统,用于氟比洛芬(FP)的局部给药。通过粒径分布、Zeta 电位分析、X 射线分析、体外经皮渗透、流变学研究、皮肤刺激性试验、体内药效学评价和体内药代动力学研究,对用于皮肤局部应用的半固体制剂进行了特征描述。NLC 在胶体范围内保持稳定,通过适当的卡波姆制剂凝胶化后均匀分散。通过大鼠皮肤的体外渗透研究表明,与负载 FP 的普通凝胶相比,FP-NLC-凝胶具有更明显的渗透特性。在三种不同温度下储存后,所有 NLC-凝胶均表现出假塑性流动和触变性。将 FP-NLC-凝胶施用于兔皮后,未见水肿和红斑,该凝胶可抑制卵清蛋白诱导的大鼠足肿胀。口服和局部给药后,血浆中的最大浓度分别为 29.44μg/ml 和 2.49μg/ml。而局部应用后药物在皮肤中的蓄积量明显高于口服应用。总之,基于 NLC 的凝胶可能是 FP 局部递药的一种有前途的载体。

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