Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity

• Published in: Pharmaceutics Vol. 15; no. 1; p. 80
• Main Authors: Zaky, Mohamed F, Megahed, Mohamed A, Hammady, Taha M, Gad, Shadeed, Ghorab, Mamdouh Mostafa, El-Say, Khalid M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-12-2022; MDPI
• Subjects: Acids; Anticoagulants; apixaban; Bioavailability; box–behnken design; Drug delivery systems; Drug dosages; Efficiency; Embolisms; in vivo pharmacokinetic; Independent variables; industrial development; Lipids; Nanoparticles; nanostructured lipid carrier; Nanotechnology; Optimization techniques; Oral administration; Particle size; Ratios; Surfactants; Thromboembolism; venous thromboembolism; Mumbai India; United States > US; Egypt; India; in vivo pharmacokinetic; box–behnken design; venous thromboembolism; anticoagulant activity; industrial development; nanostructured lipid carrier; apixaban
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15010080

Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to increase its bioavailability and effectiveness. As solid lipid, liquid lipid, hydrophilic, and lipophilic stabilizers, stearic acid, oleic acid, Tween 80, and lecithin were used, respectively. Utilizing Box-Behnken design, the effects of three factors on NLC particle size (Y
), zeta potential (Y
), and entrapment efficiency percent (Y
) were examined and optimized. The optimized formula was prepared, characterized, morphologically studied, and pharmacokinetically and pharmacodynamically assessed. The observed responses of the optimized Apx formula were 315.2 nm, -43.4 mV, and 89.84% for Y
, Y
, and Y
, respectively. Electron microscopy revealed the homogenous spherical shape of the NLC particles. The in vivo pharmacokinetic study conducted in male Wistar rats displayed an increase in AUC and C
by 8 and 2.67 folds, respectively, compared to oral Apx suspension. Moreover, the half-life was increased by 1.94 folds, and clearance was diminished by about 8 folds, which makes the NLC formula a promising sustained release system. Interestingly, the pharmacodynamic results displayed the superior effect of the optimized formula over the drug suspension with prolongation in the cuticle bleeding time. Moreover, both prothrombin time and activated partial thromboplastin time are significantly increased. So, incorporating Apx in an NLC formula significantly enhanced its oral bioavailability and pharmacodynamic activity.