TY - JOUR
T1 - Enhanced Oral Bioavailability of Rivaroxaban-Loaded Microspheres by Optimizing the Polymer and Surfactant Based on Molecular Interaction Mechanisms
AU - Choi, Min Jong
AU - Woo, Mi Ran
AU - Baek, Kyungho
AU - Park, Ji Hun
AU - Joung, Seewon
AU - Choi, Yong Seok
AU - Choi, Han Gon
AU - Jin, Sung Giu
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/8/7
Y1 - 2023/8/7
N2 - This study aimed to develop microspheres using water-soluble carriers and surfactants to improve the solubility, dissolution, and oral bioavailability of rivaroxaban (RXB). RXB-loaded microspheres with optimal carrier (poly(vinylpyrrolidone) K30, PVP) and surfactant (sodium lauryl sulfate (SLS)) ratios were prepared. 1H NMR and Fourier transform infrared (FTIR) analyses showed that drug-excipient and excipient-excipient interactions affected RXB solubility, dissolution, and oral absorption. Therefore, molecular interactions between RXB, PVP, and SLS played an important role in improving RXB solubility, dissolution, and oral bioavailability. Formulations IV and VIII, containing optimized RXB/PVP/SLS ratios (1:0.25:2 and 1:1:2, w/w/w), had significantly improved solubility by approximately 160- and 86-fold, respectively, compared to RXB powder, with the final dissolution rates improved by approximately 4.5- and 3.4-fold, respectively, compared to those of RXB powder at 120 min. Moreover, the oral bioavailability of RXB was improved by 2.4- and 1.7-fold, respectively, compared to that of RXB powder. Formulation IV showed the highest improvement in oral bioavailability compared to RXB powder (AUC, 2400.8 ± 237.1 vs 1002.0 ± 82.3 h·ng/mL). Finally, the microspheres developed in this study successfully improved the solubility, dissolution rate, and bioavailability of RXB, suggesting that formulation optimization with the optimal drug-to-excipient ratio can lead to successful formulation development.
AB - This study aimed to develop microspheres using water-soluble carriers and surfactants to improve the solubility, dissolution, and oral bioavailability of rivaroxaban (RXB). RXB-loaded microspheres with optimal carrier (poly(vinylpyrrolidone) K30, PVP) and surfactant (sodium lauryl sulfate (SLS)) ratios were prepared. 1H NMR and Fourier transform infrared (FTIR) analyses showed that drug-excipient and excipient-excipient interactions affected RXB solubility, dissolution, and oral absorption. Therefore, molecular interactions between RXB, PVP, and SLS played an important role in improving RXB solubility, dissolution, and oral bioavailability. Formulations IV and VIII, containing optimized RXB/PVP/SLS ratios (1:0.25:2 and 1:1:2, w/w/w), had significantly improved solubility by approximately 160- and 86-fold, respectively, compared to RXB powder, with the final dissolution rates improved by approximately 4.5- and 3.4-fold, respectively, compared to those of RXB powder at 120 min. Moreover, the oral bioavailability of RXB was improved by 2.4- and 1.7-fold, respectively, compared to that of RXB powder. Formulation IV showed the highest improvement in oral bioavailability compared to RXB powder (AUC, 2400.8 ± 237.1 vs 1002.0 ± 82.3 h·ng/mL). Finally, the microspheres developed in this study successfully improved the solubility, dissolution rate, and bioavailability of RXB, suggesting that formulation optimization with the optimal drug-to-excipient ratio can lead to successful formulation development.
KW - microsphere
KW - molecular interaction
KW - oral bioavailability
KW - poorly water-soluble drugs
KW - rivaroxaban
UR - http://www.scopus.com/inward/record.url?scp=85165916185&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.3c00281
DO - 10.1021/acs.molpharmaceut.3c00281
M3 - Article
C2 - 37433746
AN - SCOPUS:85165916185
SN - 1543-8384
VL - 20
SP - 4153
EP - 4164
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 8
ER -