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

Abstract

This study aimed to develop microspheres usingwater-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 wereprepared. 1H NMR and Fourier transform infrared (FTIR)analyses showed that drug−excipient and excipient−excipientinteractions affected RXB solubility, dissolution, and oralabsorption. 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 approximately160- 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- and1.7-fold, respectively, compared to that of RXB powder. Formulation IV showed the highest improvement in oral bioavailabilitycompared to RXB powder (AUC, 2400.8 ± 237.1 vs 1002.0 ± 82.3 h·ng/mL). Finally, the microspheres developed in this studysuccessfully improved the solubility, dissolution rate, and bioavailability of RXB, suggesting that formulation optimization with theoptimal drug-to-excipient ratio can lead to successful formulation development.