Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, India.
Drug Dev Ind Pharm. 2011 Aug;37(8):907-16. doi: 10.3109/03639045.2010.550050. Epub 2011 Mar 14.
Nanoemulsion (NE) of amlodipine besilate (AB) was developed by spontaneous emulsification method with the aim to enhance the solubility and oral bioavailability of AB and to achieve localized delivery of drug at target site. Pseudoternary phase diagrams were constructed to identify the NE region. The selected formulations from NE region were subjected to droplet size analysis, partitioning study and in vitro drug release. The partition coefficient was calculated and correlated with percent dissolution efficiency as a tool to predict in vitro drug release from NEs. The release of drug from NEs was significantly higher (p < 0.01) than the marketed tablet formulation. The optimal formulation contained 15% Labrafil M, 35% [Tween 80: ethanol (2:1)], and 50% by weight aqueous phase (NE3) was characterized by transmission electron microscopy (TEM) and for thermodynamic stability. The pharmacokinetics and biodistribution studies of the optimized radiolabeled formulation (99mTc-labeled) in mice (p.o.) demonstrated a relative bioavailability of 475% against AB suspension. In almost all the tested organs, the uptake of AB from NE was significantly higher (p < 0.05) than AB suspension especially in heart with a drug targeting index of 44.1%, also confirming the efficacy of nanosized formulation at therapeutic site. A three times increase in the overall residence time of NE further signifies the advantage of NEs as drug carriers for enhancing bioavailability of AB.
硝苯地平（AB）纳米乳（NE）通过自发乳化法制备，旨在提高 AB 的溶解度和口服生物利用度，并实现药物在靶部位的局部递送。构建伪三元相图以确定 NE 区域。从 NE 区域选择的配方进行粒径分析、分配研究和体外药物释放。计算分配系数并与溶解效率的百分比相关联，作为预测 NE 中药物体外释放的工具。药物从 NE 中的释放明显高于市售片剂配方（p < 0.01）。含有 15% Labrafil M、35% [吐温 80:乙醇（2:1）]和 50%重量的水相（NE3）的最佳配方通过透射电子显微镜（TEM）进行了表征，并进行了热力学稳定性研究。优化的放射性标记配方（99mTc 标记）在小鼠（po）中的药代动力学和生物分布研究表明，相对于 AB 混悬液，其相对生物利用度为 475%。在几乎所有测试的器官中，AB 从 NE 的摄取明显高于 AB 混悬液，特别是在心脏中的药物靶向指数为 44.1%，这也证实了纳米制剂在治疗部位的功效。NE 的总驻留时间增加三倍进一步表明了 NE 作为提高 AB 生物利用度的药物载体的优势。
