尼群地平负载型固体脂质纳米粒的研制与评价:蜡质和甘油酯类脂质对血浆药代动力学的影响
Development and evaluation of nitrendipine loaded solid lipid nanoparticles: influence of wax and glyceride lipids on plasma pharmacokinetics.
作者信息
Kumar Venishetty Vinay, Chandrasekar Durairaj, Ramakrishna Sistla, Kishan Veerabrahma, Rao Yamsani Madhusudan, Diwan Prakash Vamanrao
机构信息
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh 506009, India; Pharmacology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Andhra Pradesh 500007, India.
Pharmacology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Andhra Pradesh 500007, India.
出版信息
Int J Pharm. 2007 Apr 20;335(1-2):167-175. doi: 10.1016/j.ijpharm.2006.11.004. Epub 2006 Nov 3.
Nitrendipine is an antihypertensive drug with poor oral bioavailability ranging from 10 to 20% due to the first pass metabolism. For improving the oral bioavailability of nitrendipine, nitrendipine loaded solid lipid nanoparticles have been developed using triglyceride (tripalmitin), monoglyceride (glyceryl monostearate) and wax (cetyl palmitate). Poloxamer 188 was used as surfactant. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. SLN were characterized for particle size, zeta potential, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in phosphate buffer of pH 6.8 using Franz diffusion cell. Pharmacokinetics of nitrendipine loaded solid lipid nanoparticles after intraduodenal administration to conscious male Wistar rats was studied. Bioavailability of nitrendipine was increased three- to four-fold after intraduodenal administration compared to that of nitrendipine suspension. The obtained results are indicative of solid lipid nanoparticles as carriers for improving the bioavailability of lipophilic drugs such as nitrendipine by minimizing first pass metabolism.
尼群地平是一种口服生物利用度较差的抗高血压药物,由于首过代谢,其口服生物利用度在10%至20%之间。为了提高尼群地平的口服生物利用度,已使用甘油三酯(三棕榈精)、甘油单酯(单硬脂酸甘油酯)和蜡(十六烷基棕榈酸酯)制备了载有尼群地平的固体脂质纳米粒。泊洛沙姆188用作表面活性剂。采用脂质熔融物与水相的热均质化,随后在高于脂质熔点的温度下进行超声处理,以制备固体脂质纳米粒分散体。对固体脂质纳米粒的粒径、ζ电位、包封率以及脂质和药物的结晶度进行了表征。使用Franz扩散池在pH 6.8的磷酸盐缓冲液中进行体外释放研究。研究了载有尼群地平的固体脂质纳米粒在清醒雄性Wistar大鼠十二指肠给药后的药代动力学。与尼群地平混悬液相比,十二指肠给药后尼群地平的生物利用度提高了三到四倍。所得结果表明,固体脂质纳米粒作为载体,可通过最小化首过代谢来提高亲脂性药物(如尼群地平)的生物利用度。