Development of novel cilostazol–loaded solid SNEDDS using a SPG membrane emulsification technique: Physicochemical characterization and in vivo evaluation

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2017-02, Vol.150, p.216-222
• Main Authors: Mustapha, Omer, Kim, Kyung Soo, Shafique, Shumaila, Kim, Dong Shik, Jin, Sung Giu, Seo, Youn Gee, Youn, Yu Seok, Oh, Kyung Taek, Lee, Beom-Jin, Park, Young Joon, Yong, Chul Soon, Kim, Jong Oh, Choi, Han-Gon
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Bioavailability; Biological Availability; Cilostazol; Drug Carriers - chemistry; Drug Delivery Systems; Emulsion droplet size; Emulsions - chemistry; Glass; Glycerides - chemistry; Male; Membrane emulsification; Membranes, Artificial; Nanostructures; Particle Size; Polysorbates - chemistry; Porosity; Rats; Rats, Sprague-Dawley; Shirasu porous glass membrane; Solid self-nanoemulsifying drug delivery system; Solubility; Temperature; Tetrazoles - chemistry; Water - chemistry
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2016.11.039

[Display omitted] •Cilostazol-loaded solid SNEDDS was prepared using membrane emulsification technique.•It was prepared with calcium silicate as a solid carrier.•It provided smaller and more uniform nanoemulsions than the non-emulsified SNEDDS.•It gave higher drug solubility and dissolution than the non-emulsified SNEDDS.•This SNEDDS improved the oral bioavailability of cilostazol. The objective of this study was to develop a novel solid self-nanoemulsifying drug delivery system (SNEDDS) using a membrane emulsification technique involving Shirasu porous glass (SPG) which produced very small and uniform emulsion droplets, resulting in enhanced solubility, dissolution and oral bioavailability of poorly water–soluble cilostazol. The effects of carriers on the drug solubility were assessed, and pseudo-ternary phase diagrams were plotted. Among the liquid SNEDDS formulations tested, the liquid SNEDDS composed of peceol (oil), Tween 20 (surfactant) and Labrasol (cosurfactant) at a weight ratio of 15/55/30, produced the smallest emulsion droplet size. The cilostazol–loaded liquid SNEDDS formulation was suspended in the distilled water and subjected to SPG membrane emulsification. Calcium silicate was added as a solid carrier in this liquid SNEDDS, completely suspended and spray–dried, leading to the production of a cilostazol–loaded solid SNEDDS. The emulsion droplet size, solubility and dissolution of the emulsified solid SNEDDS were assessed as compared to the solid SNEDDS prepared without emulsification. Moreover, the physicochemical characteristics and pharmacokinetics in rats were evaluated with the emulsified solid SNEDDS. The emulsified solid SNEDDS provided significantly smaller and more uniform nanoemulsions than did the non-emulsified solid SNEDDS. The emulsified solid SNEDDS showed significantly higher drug solubility and dissolution as compared to the non-emulsified solid SNEDDS. The crystalline drug in it was converted into the amorphous state. Moreover, in rats, it gave significantly higher initial plasma concentrations and AUC compared to the drug powder, suggesting its improved oral bioavailability of cilostazol. Thus, this novel solid SNEDDS developed using a membrane emulsification technique represents a potentially powerful oral delivery system for cilostazol.