Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Colloids Surf B Biointerfaces. 2010 Apr 1;76(2):410-20. doi: 10.1016/j.colsurfb.2009.11.021. Epub 2009 Dec 5.
The present study aimed at developing an optimal nanoemulsion of ezetimibe and evaluating its stability, pharmacodynamic and pharmacokinetic potential. Solubility of ezetimibe was determined in various vehicles. Surfactants and cosurfactants were grouped in two different combinations to construct pseudoternary phase diagrams. Formulations were selected from the o/w nanoemulsion region and were subjected to various thermodynamic stability and dispersibility tests. Optimized formulations were characterized for their percentage transmittance, refractive index, viscosity, droplet size and zeta potential. Release rate of optimized formulations was determined using an in vitro dissolution test. The formulation used for assessment of lipid lowering potential and bioavailability contained Capryol 90 (10%, v/v), Tween 20 (33.33%, v/v), PEG 400 (16.67%, v/v), double distilled water (40%, v/v). The release of drug from the nanoemulsion formulations was extremely significant (p<0.001) in comparison to the drug suspension. More than 60% of the drug was released in the initial 1h of the dissolution study in comparison to the drug suspension. The value of total cholesterol in the group administered with the formulation PF1 was highly significant (p<0.001) with respect to the group administered with the suspension of the drug. The plasma concentration time profile of ezetimibe from nanoemulsion represented greater improvement of drug absorption than the marketed formulation and simple drug suspension. The shelf life of the nanoemulsion was found to be 5.94 years at room temperature. The present study established nanoemulsion formulation to be one of the possible alternatives to traditional oral formulations of ezetimibe to improve its bioavailability.
本研究旨在开发依泽替米贝的最佳纳米乳，并评价其稳定性、药效学和药代动力学潜力。测定了依泽替米贝在各种载体中的溶解度。将表面活性剂和助表面活性剂分为两组不同的组合，构建伪三元相图。从 o/w 纳米乳区域选择制剂，并进行各种热力学稳定性和分散性试验。对优化的制剂进行了百分透射率、折射率、粘度、粒径和 zeta 电位的特征描述。使用体外溶出试验测定优化制剂的释放速率。用于评估降脂潜力和生物利用度的制剂配方含有 Capryol 90（10%，v/v）、Tween 20（33.33%，v/v）、PEG 400（16.67%，v/v）、双蒸水（40%，v/v）。与药物混悬剂相比，药物从纳米乳制剂中的释放极其显著（p<0.001）。与药物混悬剂相比，在溶解研究的最初 1 小时内，超过 60%的药物被释放。与给予药物混悬剂的组相比，给予配方 PF1 的组的总胆固醇值具有高度显著性（p<0.001）。纳米乳制剂中依泽替米贝的血浆浓度时间曲线表明，与市售制剂和简单的药物混悬剂相比，药物吸收得到了更大的改善。纳米乳的保质期在室温下为 5.94 年。本研究建立了纳米乳制剂，作为改善依泽替米贝生物利用度的传统口服制剂的可能替代方案之一。
