Anticoagulant and Pharmacokinetic Evaluation of Apixaban Sublingual Tablets in Wistar Rats

Background

Apixaban is a novel oral anticoagulant widely used in the treatment and prevention of thromboembolic disorders. However, oral administration is associated with delayed onset of action and inaccurate gastrointestinal absorption paired with difficulties in swallowing among those people who have swallowing difficulties, which restricts its clinical applicability in some patients. Sublingual route has a fast systemic absorption and avoids first-pass metabolism in the liver.

Objectives

The current research aimed for developing and evaluating Apixaban sublingual tablet and comparing its anticoagulant effects and in vivo pharmacokinetic properties within a marketed available oral formulation.

Materials and Methods

Sublingual tablets have been formulated using direct compression method and assessed its physicochemical parameters such as hardness, thickness, friability, wetting time, disintegration time as well as in vitro drug release. The in vivo anticoagulant properties was investigated in Wistar rats using bleeding time and clotting time models, as well as, measuring mucoadhesion, retention period, and sublingual mucosal pH. Plasma sample analysis based on validated HPLC method for determine of pharmacokinetic parameters.

Results

The sublingual tablets showed rapid disintegration within 10-12 sec, good mechanical properties, and drug release exceeding 94%. Bleeding and clotting times were significantly prolonged compared with placebo and marketed tablets. The sublingual formulation achieved higher C_max (0.40±0.005 µg/mL) and AUC_0-∞ (2.146±0.010 µg/mL hr) than the marketed formulation, resulting in 11.54% higher bioavailability.

Conclusion

The sublingual tablet demonstrated excellent anticoagulant activity and improved bioavailability compared to the conventional oral formulation, making it a promising alternative for emergency or swallowing-impaired patients.