Enhanced Biopharmaceutical Performance of Rivaroxaban through Polymeric Amorphous Solid Dispersion

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Rivaroxaban (RXB), a direct Factor Xa inhibitor for venous thromboembolism (VTE), exhibits limited permeability due to P-gp efflux.
• Enhancing RXB's biopharmaceutical performance requires strategies to overcome P-gp mediated efflux and improve solubility.

Purpose of the Study:

• To investigate the potential of P-gp inhibiting polymers in amorphous solid dispersions (ASDs) to enhance rivaroxaban's solubility and permeability.
• To evaluate the impact of polymeric ASDs on the pharmacokinetic profile of rivaroxaban.

Main Methods:

• Miscibility studies using solubility and Flory-Huggins parameters.
• Preparation of binary amorphous solid dispersions using spray drying with Eudragit S100, Eudragit L100, and Soluplus.
• Characterization using DSC, PXRD, FTIR, DVS, and NMR.
• In vitro dissolution, solubility, and Caco-2 transport studies.
• In vivo pharmacokinetic studies in animals.

Main Results:

• Polymeric ASDs demonstrated superior dissolution and solubility compared to micronized rivaroxaban.
• Soluplus-based ASDs achieved a 10-fold increase in apparent solubility and maintained supersaturation for 24 hours.
• Pharmacokinetic studies showed 5.7- and 6.7-fold increases in AUC and Cmax for Soluplus ASDs.
• Reduced drug efflux ratio in Caco-2 cells indicated improved absorption for Eudragit S100 and Soluplus ASDs.

Conclusions:

• Amorphous solid dispersion with Soluplus is a promising strategy to enhance rivaroxaban's biopharmaceutical performance.
• This formulation approach effectively increases solubility and circumvents P-gp efflux, improving drug absorption and bioavailability.