Evaluation of subcutaneous forms in the improvement of pharmacokinetic profile of warfarin

We attempted to prepare a subcutaneous pharmaceutical form of warfarin based on a suspension or poly(ɛ-caprolactone) microparticles to improve patient adherence. The warfarin suspension had a mean particle size of 20.0 μm and in vitro release close to 100% in 72 h. Microparticle size and encapsulation efficiencies ranged from 54.0 to 80.0 μm and 37.0 to 47.0%, respectively. After 72 h, warfarin microparticles exhibited in vitro drug release ranging from 62.0 to 80.0%. Warfarin subcutaneous dosage forms were administered to rabbits. Plasma concentration of warfarin was determined and biological activity was measured by prothrombin time monitoring. The observed relative bioavailabilities calculated from plasma concentrations and prothrombin times were 54.2 and 92.1%, and 61.8 and 61.4% for suspension and microparticles, respectively.

Figure optionsDownload high-quality image (144 K)Download as PowerPoint slide