Category: Formulation and Quality
Purpose: The purpose of this study to develop a novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) with better dissolution and enhanced oral bioavailability of rivaroxaban.
Methods: The effect of oil and surfactants on the solubility of rivaroxaban was developed. Numerous liquid SNEDDS were prepared with peceol, TPGS and solutol HS15. The composition of SNEDDS was determined based on pseudoternary phase diagram by the droplet size. The rivaroxaban loaded S-SNEDDS containing the liquid SNEDDS and calcium silicate (porous carrier) was prepared with spray dryer. Their physicochemical properties were evaluated using emulsion droplet size analysis, DSC, SEM and PXRD. Moreover, the solubility, dissolution and pharmacokinetics of the selected S-SNEDDS were assessed compared to rivaroxaban powder.
Results: The S-SNEDDS composed of peceol/TPGS/solutol HS15 (30/25/45, v/v/v) provided an emulsion droplet size of less than 300 nm. In this S-SNEDDS, it considerably improved the solubility and dissolution compared to rivaroxaban powder. The S-SNEDDS gave 2.0-fold increased dissolution rate. Moreover, the S-SNEDDS gave better oral bioavailability (AUC and Cmax) than rivaroxaban powder. The S-SNEDDS gave 1.6-fold increased AUC values than rivaroxaban powder in rats. The physicochemical analysis showed that S-SNEEDS was existed in the amorphous form.
Conclusion: This S-SNEDDS composed of peceol/TPGS/solutol HS15 (30/25/45, v/v/v) would be recommended as a powerful oral drug delivery system for an water insoluble drug, rivaroxaban.
Ji eun Choi– Cheonan-si, Ch'ungch'ong-namdo, Republic of Korea
Kyung Ho Baek– Student, n/a, Cheonan-si, Ch'ungch'ong-namdo, Republic of Korea
Yoo Jin Choi– Ansan, Kyonggi-do, Republic of Korea
Mi Ran Woo– Ansan-si, Kyonggi-do, Republic of Korea
Jung Suk Kim– Student, Hanyang University, Ansan-si, Kyonggi-do, Republic of Korea
Dong Shik Kim– Hanyang University, Ansan, Kyonggi-do, Republic of Korea
Han-Gon Choi– College of Pharmacy, Hanyang University, South Korea, Ansan-si, Kyonggi-do, Republic of Korea
Sung Giu Jin– Department of Pharmaceutical Engineering, Dankook University, South Korea, Cheonan-si, Ch'ungch'ong-namdo, Republic of Korea