Full Factorial Design and Optimization of Olmesartan Medoxomil–Loaded Oily-Core Polymeric Nanocapsules with Improved In-Vitro Stability

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