Department of Pharmaceutics, Hamdard Nagar, Jamia Hamdard, New Delhi 110062, India.
Int J Pharm. 2011 Jan 17;403(1-2):46-56. doi: 10.1016/j.ijpharm.2010.10.018. Epub 2010 Oct 20.
The goals of the current study were to develop and characterize a nanoemulsion of ezetimibe, evaluate its stability, lipid lowering and pharmacokinetic profile. Solubility of the drug was estimated in various oils and surfactants. Existence of nanoemulsion region was confirmed by plotting phase diagrams. Various thermodynamic stability and dispersibility tests were performed on the formulations chosen from phase diagram. Percentage transmittance, refractive index, viscosity, droplet size and zeta potential of the optimized formulations were determined. Dialysis bag method was employed to study the release rate. The formulation selected for bioavailability estimation contained Capryol 90 (10%, v/v), Crempophor EL (11.25%, v/v), Transcutol(®) P (33.75%, v/v), and double distilled water (45%, v/v). The release rate from the nanoemulsion was highly significant (p<0.001) in contrast to the drug suspension. The level of total cholesterol in the group receiving nanoemulsion CF1 was found to be highly significant (p<0.001) in comparison to the group receiving drug suspension. Bioavailability studies in rats revealed superior absorption of ezetimibe from nanoemulsion as compared to the marketed formulation and drug suspension. The shelf life of the nanoemulsion was estimated to be 18.53 months. The present study corroborated nanoemulsion to be a promising choice to improve the bioavailability of ezetimibe.
本研究的目的是开发和表征依泽替米贝的纳米乳，并评估其稳定性、降血脂作用和药代动力学特征。评估了该药物在各种油和表面活性剂中的溶解度。通过绘制相图来确认纳米乳区域的存在。通过对相图中选择的配方进行各种热力学稳定性和分散性测试。对优化后的配方的透光率百分比、折射率、粘度、粒径和 Zeta 电位进行了测定。采用透析袋法研究了释放率。用于生物利用度评估的配方包含 Capryol 90（10%，v/v）、Crempophor EL（11.25%，v/v）、Transcutol® P（33.75%，v/v）和双蒸水（45%，v/v）。与药物混悬剂相比，纳米乳的释放速率具有高度显著性差异（p<0.001）。与接受药物混悬剂的组相比，接受纳米乳 CF1 的组的总胆固醇水平具有高度显著性差异（p<0.001）。大鼠的生物利用度研究表明，与市售制剂和药物混悬剂相比，纳米乳对依泽替米贝的吸收更优。纳米乳的保质期估计为 18.53 个月。本研究证实纳米乳是提高依泽替米贝生物利用度的一种很有前途的选择。
