Fixed combination of rivaroxaban and Aspirin: Tablet formulation and analytical method validation

Rivaroxaban and aspirin are commonly used antithrombotic agents in combination to prevent coronary artery disease (CAD) and atherothrombotic events in adult patients after acute coronary syndrome (ACS) with elevated cardiac biomarkers, or with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) in high-risk patients. The recommended dosage is 2.5 mg rivaroxaban twice daily in combination with 75-100 mg aspirin once daily. This study aimed to develop a fixed-dose combination tablet of rivaroxaban (2.5 mg) and aspirin (50 mg) to enhance medication adherence and decrease pill burden. Compatibility studies were conducted on the active ingredients to develop the product formula. The formula and the manufacturing procedure were chosen based on the risk assessment for each active substance, wet granulation with both actives intragranular was found to have faster dissolution than direct mix formulae. Furthermore, a validated reverse-phase HPLC stability indicator method was developed to detect APIs and their possible degradants.