Design and Optimization of Rivaroxaban-Cyclodextrin-Polymer Triple Complex Formulation with Improved Solubility

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Rivaroxaban (RIV), a direct factor Xa inhibitor, has poor solubility, necessitating administration with meals for optimal absorption.
• This limitation can lead to variable efficacy due to inconsistent patient adherence to mealtime dosing.

Purpose of the Study:

• To enhance rivaroxaban (RIV) solubility and dissolution rate.
• To develop a stable drug formulation for consistent RIV efficacy, irrespective of meal intake.
• To improve patient compliance and reduce dosing errors.

Main Methods:

• Utilized a hydroxypropyl-beta-cyclodextrin (CD)-water-soluble polymer triple complex (R-C-P complex) to improve RIV solubility.
• Employed Minitab for experimental design, optimizing CD amount, polymer amount, and polymer type.
• Evaluated RIV solubility and dissolution rates in various pH media.

Main Results:

• An optimal R-C-P complex formulation using CD and HPMC 2208 demonstrated superior RIV solubilization.
• The RIV within the complex was in an amorphous state, exhibiting high solubility and a 100% dissolution rate.
• The formulation achieved complete RIV release across different pH conditions, outperforming commercial products.

Conclusions:

• The developed R-C-P complex formulation significantly enhances RIV solubility and dissolution.
• This advancement enables consistent RIV administration, independent of meal consumption.
• The improved formulation minimizes the risk of efficacy variations caused by patient dosing errors.