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

초록

This study aimed to develop microspheres using water-solublecarriersand surfactants to improve the solubility, dissolution, and oral bioavailabilityof rivaroxaban (RXB). RXB-loaded microspheres with optimal carrier(poly(vinylpyrrolidone) K30, PVP) and surfactant (sodium lauryl sulfate(SLS)) ratios were prepared. H-1 NMR and Fourier transforminfrared (FTIR) analyses showed that drug-excipient and excipient-excipientinteractions affected RXB solubility, dissolution, and oral absorption.Therefore, molecular interactions between RXB, PVP, and SLS playedan important role in improving RXB solubility, dissolution, and oralbioavailability. Formulations IV and VIII, containing optimized RXB/PVP/SLSratios (1:0.25:2 and 1:1:2, w/w/w), had significantly improved solubilityby approximately 160- and 86-fold, respectively, compared to RXB powder,with the final dissolution rates improved by approximately 4.5- and3.4-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. FormulationIV showed the highest improvement in oral bioavailability comparedto RXB powder (AUC, 2400.8 & PLUSMN; 237.1 vs 1002.0 & PLUSMN; 82.3 h & BULL;ng/mL).Finally, the microspheres developed in this study successfully improvedthe solubility, dissolution rate, and bioavailability of RXB, suggestingthat formulation optimization with the optimal drug-to-excipient ratiocan lead to successful formulation development.

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