Comparison of the physicochemical properties, aqueous solubility, and oral bioavailability of rivaroxaban-loaded high-pressure homogenised and Shirasu porous glass membrane emulsified solid self-nanoemulsifying drug delivery systems

Abstract

This study aimed to compare high-pressure homogenization (HPH) and Shirasu porous glass (SPG) membrane emulsification for enhancing the oral bioavailability of rivaroxaban using a self-nanoemulsifying drug delivery system (SNEDDS). The effects of two different solidifying agents (calcium silicate and colloidal silica), used in SNEDDS, on the nanoemulsion system were investigated. Liquid SNEDDS comprised 30/25/45 (w/w/w) Peceol/TPGS/Solutol HS15. The optimised HPH conditions were 1500 bar with one cycle. The SPG emulsifying time and agitation speed were set at 30 min and 100 rpm, respectively. Three different liquid SNEDDS formulations (untreated, HPH, and SPG membrane emulsified) were suspended with calcium silicate and colloidal silica and spray-dried to fabricate six solid SNEDDS formulations. The crystalline state of the drug changed to an amorphous state in all SNEDDS. The formulations solidified with calcium silicate had a finer droplet size and higher aqueous solubility than those solidified with colloidal silica. Comparing two techniques, HPH exhibited a superior nanoemulsion property, aqueous solubility and dissolution rate (%) to SPG membrane emulsification. Therefore, high-pressure homogenised SNEDDS solidified with calcium silicate was selected as the appropriate solid SNEDDS. Subsequently, an in vivo study was performed using a rat model, and the selected solid SNEDDS significantly enhanced the oral bioavailability of rivaroxaban than that of the pure drug powder. In conclusion, HPH and calcium silicate are suitable emulsifying techniques and solidifying agents for producing fine nanoemulsions and enhancing the oral bioavailability of rivaroxaban in SNEDDS. © 2021 Elsevier B.V.