Arun Jagdish Kumar, Vodeti Rajeshwar, Shrivastava Birendra, Bakshi Vasudha
School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur, Rajasthan-302 017, India.
School of Pharmacy, ANURAG Group of Institutions, Venkatapur (V), Ghatkesar (M) Medchal (Dist.), Hyderabad, Telangana-500 038, India.
Adv Pharm Bull. 2020 Jul;10(3):379-388. doi: 10.34172/apb.2020.046. Epub 2020 May 11.
The present work endeavors to report a systematic approach of developing the lipidic self-nanoemulsifying formulation of olmesartan medoxomil (OMT) on the principles of Quality by Design (QbD). For preparing the self-nanoemulsifying formulation, a mixture of oil, surfactant and cosurfactant were used as vehicles. The excipients were selected after screening by solubility as well as pseudoternary phase titration studies. Mixture design was adopted for systematic optimization of the composition of nanolipidic formulations, which were evaluated for smaller globule size, stable zeta potential and lower values of polydispersity index. The optimized liquid self-nanoemulsifying formulation was identified using numerical and graphical optimization techniques, followed by validation of the experimental model. Solidification of self-nanoemulsifying formulation was carried out using porous carriers, and then optimized on the basis of oil adsorption potential, powder flow property and drug release performance. Pharmacokinetic study was performed in male Wistar rats for evaluating the drug absorption parameters. All the experimental data obtained were subjected to statistical analysis using oneway ANOVA followed by post hoc analysis using Student's t test. The optimized liquid self-nanoemulsifying formulation showed globule size <100 nm, emulsification efficiency <5 minutes and drug release >85% within in 30 minutes. Further, the solid SNEDDS formulation was effectively formulated using Neusilin US2 with maximum oil adsorption capacity and good micromeritic properties. Pharmacokinetic evaluation indicated 4 to 5-folds increase ( <0.05) in the values of C, AUC, and reduction in T from the nanoformulations vis-à-vis the marketed formulation. Overall, the developed nanolipidic formulation of olmesartan indicated superior efficacy in augmenting the drug dissolution and absorption performance.
本研究致力于报告一种基于质量源于设计（QbD）原则开发奥美沙坦酯（OMT）脂质自纳米乳化制剂的系统方法。为制备自纳米乳化制剂，使用油、表面活性剂和助表面活性剂的混合物作为载体。通过溶解度筛选以及伪三元相滴定研究后选择辅料。采用混合设计对纳米脂质制剂的组成进行系统优化，评估其较小的球粒尺寸、稳定的zeta电位和较低的多分散指数值。使用数值和图形优化技术确定优化后的液体自纳米乳化制剂，随后对实验模型进行验证。使用多孔载体对自纳米乳化制剂进行固化，然后根据油吸附潜力、粉末流动性和药物释放性能进行优化。在雄性Wistar大鼠中进行药代动力学研究以评估药物吸收参数。对获得的所有实验数据进行单因素方差分析，随后使用学生t检验进行事后分析。优化后的液体自纳米乳化制剂显示球粒尺寸<100 nm，乳化效率<5分钟，30分钟内药物释放>85%。此外，使用具有最大油吸附容量和良好粉体学性质的Neusilin US2有效地制备了固体自纳米乳化药物递送系统（SNEDDS）制剂。药代动力学评估表明，与市售制剂相比，纳米制剂的C、AUC值增加了4至5倍（<0.05），T值降低。总体而言，所开发的奥美沙坦纳米脂质制剂在增强药物溶解和吸收性能方面显示出优异的疗效。
