Enhanced Oral Bioavailability of Rivaroxaban-Loaded Microspheres by Optimizing the Polymer and Surfactant Based on Molecular Interaction Mechanisms

Min Jong Choi, Mi Ran Woo, Kyungho Baek, Ji Hun Park, Seewon Joung, Yong Seok Choi, Han Gon Choi, Sung Giu Jin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4153-4164
Number of pages12
JournalMolecular Pharmaceutics
Volume20
Issue number8
DOIs
StatePublished - 7 Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.

Keywords

  • microsphere
  • molecular interaction
  • oral bioavailability
  • poorly water-soluble drugs
  • rivaroxaban

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