Purpose

This study aims to design oily-core nanocapsules for poorly water-soluble antihypertensive drug olmesartan medoxomil (OM) and optimize systematically the in-vitro characteristics of prepared nanosystems. The study represents an organized methodology for screening and studying significant parameters affecting polymeric nanocapsule formulation and characterization.

Method

A full two-level (2³) factorial design was conducted to optimize the characteristics of poly-Ɛ-caprolactone oily-core nanocapsules (ONC) which were prepared using interfacial deposition of preformed polymer technique. The selected independent variables were the concentration of polymer, aqueous/organic phase ratio, and magnetic stirring rate.

Results

The selected formulation and processing variables significantly affected the tested responses. The developed ONC formulae showed a particle size (PS) range from 180.63 ± 0.31 to 338.93 ± 0.42 nm, polydispersity index values (PDI) were < 0.5, negative zeta potential (ZP) values from 20.17 ± 0.21 to 32.83 ± 0.21 mV, and entrapment efficiency (EE) values range from 74.63 ± 0.15 to 93.37 ± 0.15%. In-vitro drug release testing showed a controlled release pattern for OM over 8 h following Hixson-Crowell model for the optimized formula. Transmission electron micrographs (TEM) showed a perfect spherical nanocapsule with a clear polymeric coat. Stability study for 3 months at refrigerated and room temperatures showed non-significant variations and excellent stability for the prepared colloidal nanocapsular dispersion in terms of particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE).

Conclusion

It is concluded that ONC are such a promising nanosystem which can significantly improve the biopharmaceutical behavior of OM.

中文翻译：

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具有改善的体外稳定性的奥美沙坦Medoxomil负载油核聚合物纳米胶囊的全因子设计和优化

目的

这项研究旨在为水溶性差的降压药奥美沙坦medoxomil（OM）设计油性核纳米胶囊，并系统地优化所制备纳米系统的体外特性。这项研究代表了一种有组织的方法，用于筛选和研究影响聚合物纳米胶囊配方和表征的重要参数。

方法

进行了完整的两级（2 ³）析因设计，以优化使用预制聚合物的界面沉积技术制备的聚ε-己内酯油性核纳米胶囊（ONC）的特性。选择的独立变量是聚合物的浓度，水/有机相比和磁力搅拌速率。

结果

选择的配方和加工变量会显着影响测试的响应。已开发的ONC公式显示粒径（PS）为180.63±0.31至338.93±0.42 nm，多分散指数值（PDI）<0.5，负ζ电势（ZP）值为20.17±0.21至32.83±0.21 mV，以及捕集效率（EE）值范围从74.63±0.15到93.37±0.15％。体外药物释放测试显示，按照优化配方的Hixson-Crowell模型，OM在8小时内具有可控的释放模式。透射电子显微照片（TEM）显示具有透明聚合物涂层的完美球形纳米胶囊。在冷藏和室温下3个月的稳定性研究表明，所制备的胶体纳米胶囊分散体的粒径（PS）无明显变化，且稳定性极佳，

结论

结论是，ONC是一种很有前途的纳米系统，可以显着改善OM的生物药物性能。