Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus, Changa-388 421, Anand, Gujarat, India.
Graduate School of Pharmacy, Gujarat Technological University, Ahmedabad, Gujarat, India.
Int J Pharm. 2020 Jul 30;585:119486. doi: 10.1016/j.ijpharm.2020.119486. Epub 2020 Jun 2.
Epilepsy is the noncommunicable and chronic central nervous system disorder characterized by frequent, unprovoked seizures, or electrical disturbances in the brain. Topiramate is used as an antiepileptic drug for the treatment of partial onset seizures, generalized seizures and Lennox-Gastaut Syndrome. Topiramate, a BCS class II drug, has a relatively low bioavailability. It is also a substrate of P-glycoprotein and Blood Brain Barrier restricts its entry into the brain. This investigation was aimed to prepare O/W nanoemulsion delivery system of topiramate to improve its brain bioavailability. Topiramate loaded nanoemulsion was prepared by phase titration method. It was consisting of 2% w/w Capmul MCM C8, 32% w/w Tween 20:Carbitol (2:1) and 66% w/w water. It was characterized for globule size, viscosity, polydispersibility index, zeta potential, pH, conductivity values, transmittance and TEM. Pharmacodynamic, pharmacokinetic and brain drug uptake study was carried out using wistar albino rats post intranasal and oral administration. Topiramate loaded nanoemulsion was having a globule size of 4.73 ± 0.52 nm. It was stable for six months. Brain uptake of topiramate post intranasal administration of topiramate loaded nanoemulsion was significantly (P < 1.86 × 10) higher when it was compared with oral administration of topiramate loaded nanoemulsion. This study indicates that intranasal administration of topiramate containing nanoemulsion could be an encouraging approach for the treatment of epilepsy to minimize the dose of topiramate in direction to avoid dose related adverse events.
癫痫是一种非传染性的慢性中枢神经系统疾病，其特征是频繁、无诱因的癫痫发作或大脑电活动紊乱。托吡酯作为一种抗癫痫药物，用于治疗部分发作性癫痫、全身性癫痫和 Lennox-Gastaut 综合征。托吡酯是一种 BCS Ⅱ类药物，其生物利用度相对较低。它也是 P-糖蛋白的底物，血脑屏障限制其进入大脑。本研究旨在制备托吡酯的 O/W 纳米乳给药系统，以提高其脑生物利用度。采用相滴定法制备载托吡酯纳米乳。它由 2%w/w Capmul MCM C8、32%w/w Tween 20:Carbitol（2:1）和 66%w/w 水组成。对其粒径、粘度、多分散指数、Zeta 电位、pH 值、电导率、透光率和 TEM 进行了表征。通过 Wistar 白化大鼠进行了鼻腔内和口服给药后的药效学、药代动力学和脑内药物摄取研究。载托吡酯纳米乳的粒径为 4.73±0.52nm。它在六个月内是稳定的。与口服载托吡酯纳米乳相比，鼻腔内给予载托吡酯纳米乳后，托吡酯的脑摄取显著增加（P<1.86×10）。本研究表明，鼻腔内给予载托吡酯纳米乳可能是治疗癫痫的一种有前途的方法，以尽量减少托吡酯的剂量，避免与剂量相关的不良反应。
