Department of Pharmaceutics, College of Pharmacy, Jouf University, P.O. Box 2014, Skaka, Saudi Arabia; Department of Pharmaceutics and Ind. Pharmacy, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt.
Department of Pharmaceutics, College of Pharmacy, Jouf University, P.O. Box 2014, Skaka, Saudi Arabia; Department of Pharmaceutics and Ind. Pharmacy, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt.
Int J Pharm. 2018 Oct 25;550(1-2):359-371. doi: 10.1016/j.ijpharm.2018.08.062. Epub 2018 Sep 1.
Carbamazepine is a valuable pharmacological agent prescribed in treatment of epilepsy and trigeminal neuralgia. Poor bioavailability, successive dose adjustments and reported long term toxic effects are the main hurdles associated with carbamazepine oral administration. Bees wax containing NLC formulations were developed using high shear homogenization/sonication technique to overcome drug limitations. Formulations were successfully produced and evaluated for both in vitro and in vivo assessments. Results showed particles in nanometric range with negative surface charge and satisfying encapsulation efficiencies (from 93.1 ± 7.6 to 95.7 ± 5.6%). In vitro release studies revealed biphasic pattern and faster release was accompanied with higher bees wax concentration. Interaction between drug and NLC components was assessed using infrared and thermal analysis. Using validated chromatographic analytical method, selected formulation showed good pharmacokinetic profile depriving from plasma fluctuation with 2.27-fold and 1.83-fold improved bioavailability compared to conventional drug suspension and Tegretol™ suspension respectively. It also showed stronger anticonvulsant activity, with respect to conventional drug suspension, in terms of seizure latency, frequency and duration. Toxicity studies revealed undetectable liver or testicular toxicity in biochemical, histological and immunohistochemical investigations verifying its superiority above other investigated formulations. Collectively, results indicate potential suitability of NLC system to effectively and safely deliver carbamazepine orally.
卡马西平是一种有价值的药理学药物，用于治疗癫痫和三叉神经痛。生物利用度低、连续剂量调整和报告的长期毒性作用是与卡马西平口服相关的主要障碍。使用高剪切匀化/超声技术开发了含有蜂蜡的 NLC 制剂，以克服药物限制。成功制备了制剂，并进行了体外和体内评估。结果表明，颗粒处于纳米级范围，具有负表面电荷，包封效率令人满意（从 93.1±7.6%到 95.7±5.6%）。体外释放研究显示出双相模式，随着蜂蜡浓度的增加，释放速度更快。使用红外和热分析评估药物与 NLC 成分之间的相互作用。使用经过验证的色谱分析方法，所选制剂表现出良好的药代动力学特征，与普通药物混悬剂和 Tegretol™混悬剂相比，可使血浆波动降低 2.27 倍和 1.83 倍，生物利用度得到提高。与普通药物混悬剂相比，它还显示出更强的抗惊厥活性，在潜伏期、频率和持续时间方面。毒性研究表明，在生化、组织学和免疫组织化学研究中未检测到肝或睾丸毒性，证实其优于其他研究制剂。总的来说，结果表明 NLC 系统具有有效和安全地口服递送卡马西平的潜力。
