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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Formulation Development

Background:

• Rivaroxaban (RXB) exhibits poor aqueous solubility, limiting its oral bioavailability.
• Developing effective drug delivery systems is crucial for enhancing the therapeutic efficacy of poorly soluble drugs like rivaroxaban.

Purpose of the Study:

• To develop rivaroxaban-loaded microspheres using water-soluble carriers and surfactants.
• To improve the solubility, dissolution rate, and oral bioavailability of rivaroxaban through optimized formulation.

Main Methods:

• Microspheres were prepared using poly(vinylpyrrolidone) K30 (PVP) as a carrier and sodium lauryl sulfate (SLS) as a surfactant.
• Drug-excipient and excipient-excipient interactions were analyzed using 1H NMR and FTIR.
• Solubility, dissolution rates, and oral bioavailability were evaluated for optimized formulations.

Main Results:

• Optimized rivaroxaban/PVP/SLS microsphere formulations (IV and VIII) showed 160- and 86-fold solubility increases, respectively, compared to rivaroxaban powder.
• Dissolution rates at 120 min improved by approximately 4.5- and 3.4-fold for formulations IV and VIII.
• Oral bioavailability was enhanced by 2.4-fold (formulation IV) and 1.7-fold (formulation VIII), with formulation IV exhibiting the highest increase (AUC: 2400.8 ± 237.1 h·ng/mL).

Conclusions:

• The developed microspheres effectively improved rivaroxaban's solubility, dissolution rate, and oral bioavailability.
• Molecular interactions between rivaroxaban, PVP, and SLS are critical for enhancing drug properties.
• Optimizing drug-to-excipient ratios is essential for successful rivaroxaban formulation development using this approach.