Nooli Mounika, Chella Naveen, Kulhari Hitesh, Shastri Nalini R, Sistla Ramakrishna
a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) - Hyderabad , Hyderabad , India.
b Medicinal Chemistry and Pharmacology Division , Council of Scientific and Industrial Research-Indian Institute of Chemical Technology (CSIR-IICT) , Hyderabad , India.
Drug Dev Ind Pharm. 2017 Apr;43(4):611-617. doi: 10.1080/03639045.2016.1275666. Epub 2017 Jan 8.
Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability (28%) resulting from poor aqueous solubility, presystemic metabolism and P-glycoprotein mediated efflux. The present investigation studies the role of lipid nanocarriers in enhancing the OLM bioavailability through oral delivery.
Solid lipid nanoparticles (SLN) were prepared by solvent emulsion-evaporation method. Statistical tools like regression analysis and Pareto charts were used to detect the important factors effecting the formulations. Formulation and process parameters were then optimized using mean effect plot and contour plots. The formulations were characterized for particle size, size distribution, surface charge, percentage of drug entrapped in nanoparticles, drug-excipients interactions, powder X-ray diffraction analysis and drug release in vitro.
The optimized formulation comprised glyceryl monostearate, soya phosphatidylcholine and Tween 80 as lipid, co-emulsifier and surfactant, respectively, with an average particle size of 100 nm, PDI 0.291, zeta potential of -23.4 mV and 78% entrapment efficiency. Pharmacokinetic evaluation in male Sprague Dawley rats revealed 2.32-fold enhancement in relative bioavailability of drug from SLN when compared to that of OLM plain drug on oral administration.
In conclusion, SLN show promising approaches as a vehicle for oral delivery of drugs like OLM.
奥美沙坦酯（OLM）是一种抗高血压药物，由于其水溶性差、首过代谢以及P-糖蛋白介导的外排作用，口服生物利用度较低（28%）。本研究旨在探讨脂质纳米载体在通过口服给药提高OLM生物利用度方面的作用。
采用溶剂乳化蒸发法制备固体脂质纳米粒（SLN）。使用回归分析和帕累托图等统计工具来检测影响制剂的重要因素。然后使用平均效应图和等高线图对制剂和工艺参数进行优化。对制剂的粒径、粒径分布、表面电荷、纳米粒中药物包封率、药物-辅料相互作用、粉末X射线衍射分析和体外药物释放进行了表征。
优化后的制剂分别包含单硬脂酸甘油酯、大豆磷脂酰胆碱和吐温80作为脂质、助乳化剂和表面活性剂，平均粒径为100nm，多分散指数（PDI）为0.291，ζ电位为-23.4mV，包封率为78%。雄性Sprague Dawley大鼠的药代动力学评价显示，口服给药时，与OLM普通药物相比，SLN中药物的相对生物利用度提高了2.32倍。
总之，SLN作为一种口服给药载体，对于OLM这类药物显示出有前景的应用方法。
