Apixaban Ultrafine O/W Nano Emulsion Transdermal Drug Delivery System: Formulation, In Vitro and Ex Vivo Characterization

Abstract

Mustafa R. Abdulbaqi, N A Rajab.

Apixaban (APX) is a potent oral anticoagulant drug that directly inhibit coagulation factor Xa for prevention of venous thromboembolism (VTE) following total hip or knee replacement surgery. Orally APX has poor water solubility (0.028 mg/mL) and relative low bioavailability (50%). Transdermal APX delivery was utilized as a convenient alternative route to control oral limitations. This study designed to formulate ultrafine APX o/w nanoemulsion with self-permeation enhancing properties through skin barrier utilizing the ultrafine (> 50 nm) nanosized droplets as well as nanoemulsion components themselves to act as a permeation enhancer. Solubility study result in selecting triacetin oil, triton-x-100 and carbitol as oil phase, surfactant and cosurfactant respectively, while pseudoternary phase diagram construct nanoemulsion area for choosing formulations. Twenty-one o/w nanoemulsions prepared and characterized for droplet size, pH values, percent transmittance, electroconductivity, APX content, in vitro APX release, and ex vivo permeation through Albino Wistar rat abdominal skin to simulate human skin. Among formulations, ten preparations demonstrate ultrafine APX o/w nanoemulsions with high percent transmittance and electroconductivity, pH values appropriate for skin application, ultrafine droplet sizes (> 50 nm) and accepted APX content. In vitro release studies reveal significant (p ≤ 0.05) increase in APX dispersibility and diffusion through dialysis membrane. Ex vivo APX permeation through rat abdominal skin was significantly (p ≤ 0.05) increased in comparison with pure drug as assured by significant (p ≤ 0.05) enhancement in permeation parameters Jss, KP and ER with shorter Tlag, which could be attributed to permeation enhancing properties of nanoemulsion formulation itself.