Motawea Amira, Borg Thanaa, Abd El-Gawad Abd El-Gawad H
a Department of Pharmaceutics, Faculty of Pharmacy , Mansoura University , Mansoura , Egypt.
Drug Dev Ind Pharm. 2018 Jan;44(1):144-157. doi: 10.1080/03639045.2017.1386204. Epub 2017 Oct 17.
Phenytoin (PHT) is an antiepileptic drug that was reported to exhibit high wound healing activity. Nevertheless, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop, characterize nanostructured lipid carriers (NLCs), and evaluate their potential in topical delivery of PHT to improve the drug entrapment efficiency and sustained release. The NLCs were prepared by hot homogenization followed by ultra sonication method using 2 factorial design. NLC formulations were characterized regarding their particle size (PS), zeta potential (ZP), entrapment efficiency percent (%EE), surface morphology, physicochemical stability, and in vitro release studies. The optimized NLC (F7) was further incorporated in 1%w/v carbopol gel and then characterized for appearance, pH, viscosity, stability, and in vitro drug release. The prepared NLCs were spherical in shape and possessed an average PS of 121.4-258.2 nm, ZP of (-15.4)-(-32.2) mV, and 55.24-88.80 %EE. Solid-state characterization revealed that the drug is dispersed in an amorphous state with hydrogen bond interaction between the drug and the NLC components. NLC formulations were found to be stable at 25 °C for six months. The stored F7-hydrogel showed insignificant changes in viscosity and drug content (p>.05) up to six months at 25 °C that pave a way for industrial fabrication of efficient PHT products. In vitro release studies showed a sustained release from NLC up to 48 h at pH 7.4 following non-Fickian Higuchi kinetics model. These promising findings encourage the potential use of phenytoin loaded lipid nanoparticles for future topical application.
苯妥英（PHT）是一种抗癫痫药物，据报道具有较高的伤口愈合活性。然而，其溶解度有限、生物利用度低以及局部给药时分布效率低下限制了其应用。因此，本研究旨在开发、表征纳米结构脂质载体（NLCs），并评估其在PHT局部给药中的潜力，以提高药物包封效率和缓释效果。采用2因子设计，通过热均质化随后超声处理的方法制备NLCs。对NLC制剂的粒径（PS）、zeta电位（ZP）、包封效率百分比（%EE）、表面形态、物理化学稳定性和体外释放研究进行了表征。将优化后的NLC（F7）进一步加入1%w/v的卡波姆凝胶中，然后对其外观、pH值、粘度、稳定性和体外药物释放进行表征。制备的NLCs呈球形，平均PS为121.4 - 258.2nm，ZP为（-15.4）-（-32.2）mV，%EE为55.24 - 88.80%。固态表征表明药物以无定形状态分散，药物与NLC成分之间存在氢键相互作用。发现NLC制剂在25°C下6个月内稳定。在25°C下储存6个月，储存的F7水凝胶的粘度和药物含量变化不显著（p>0.05），这为高效PHT产品的工业化生产铺平了道路。体外释放研究表明，在pH 7.4条件下，NLCs遵循非菲克- Higuchi动力学模型可持续释放长达48小时。这些有前景的发现鼓励了负载苯妥英的脂质纳米颗粒在未来局部应用中的潜在用途。
