Apixaban and clopidogrel in a fixed-dose combination: Formulation and in vitro evaluation

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Cardiovascular Pharmacology

Background:

• Fixed-dose combination (FDC) products offer a safe and cost-effective approach to medication.
• Concurrent use of anticoagulants and antiplatelet agents is prevalent in cardiovascular patients.

Purpose of the Study:

• To formulate a fixed-dose combination (FDC) tablet containing Apixaban and Clopidogrel.
• To develop extended-release Apixaban and immediate-release Clopidogrel for thrombo-embolic event prophylaxis and treatment.

Main Methods:

• Apixaban extended-release tablets were formulated using design expert software and various polymers.
• Clopidogrel immediate-release tablets were developed using different diluents.
• Both formulations underwent direct compression and wet granulation, followed by dissolution profiling and encapsulation.

Main Results:

• Apixaban release followed zero-order kinetics, primarily governed by super case II transport.
• Polymer type and concentration significantly impacted Apixaban release rate (P < 0.05), with increased HPMC retarding release.
• Optimized Clopidogrel tablets with spray-dried lactose and sodium stearyl fumarate exhibited good stability and properties.

Conclusions:

• An optimal FDC formulation was achieved, providing 24-hour extended release of Apixaban and immediate release of Clopidogrel.
• The study demonstrates successful development of a dual-action tablet for managing thrombo-embolic risks.