(W1130-03-16) Development of Enhanced the Physicochemical Properties, Solubility, and Oral Bioavailability of Rivaroxaban-Loaded Solid Self-nanoemulsifying Drug Delivery Systems

Purpose: This study aimed to compare high-pressure homogenizer (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 (colloidal silica and calcium silicate), used in SNEDDS, on the nanoemulsion system were investigated.

Methods: Liquid SNEDDS comprised 30/25/45 (w/w/w) Peceol/TPGS/Solutol HS15. Three different liquid SNEDDS formulations (untreated, HPH, and SPG membrane emulsified) were suspended with colloidal silica and calcium silicate and spray-dried to fabricate six solid SNEDDS formulations; the physicochemical properties, aqueous solubility, and dissolution profiles of all formulations were compared. Subsequently, the formulation with the highest drug solubility and dissolution rate (%) was studied in vivo in rats.

Results: The SPG emulsifying time and agitation speed were set at 100 rpm and 30 min. The optimised HPH conditions were 1500 bar with one cycle, respectively. Comparing two techniques, HPH exhibited a superb nanoemulsion property, aqueous solubility and dissolution rate (%) to SPG membrane emulsification. When the two mesoporous materials were compared, calcium silicate contributed to creating smaller droplets than that did colloidal silica. Furthermore, the aqueous solubility and dissolution profile of high-pressure homogenised solid SNEDDS (calcium silicate) was the highest (41- and 1.9-fold increases in aqueous solubility and dissolution rate (%, at 45 min), respectively). As a result, high-pressure homogenised SNEDDS solidified with calcium silicate was selected as the appropriate solid SNEDDS. Afterward, an in vivo study was performed using a rat model, and the selected solid SNEDDS significantly improved the oral bioavailability of rivaroxaban than that of the pure drug powder.

Conclusion: Therefore, HPH and calcium silicate are suitable emulsifying techniques and solidifying agents, respectively, for producing fine nanoemulsions and enhancing the oral bioavailability of rivaroxaban in SNEDDS.