Taste-Masked Microparticles of Sodium Warfarin Prepared by Hot Melt Extrusion and Thermal Postprocessing

Background/Objectives. Warfarin possesses a bitter taste and requires a personalized dose in the range of 4.5 to 77 mg per week. This study investigated the potential for personalizing warfarin dosing by developing taste-masked matrix pellets. Pellets, supposedly, can be counted and orally administered in the required quantity to obtain the required dose. Methods. The study evaluated the effects of drug load (10, 20, and 30 wt.%) on the duration of thermal postprocessing (to achieve the desired aspect ratio) and drug release. The warfarin sodium clathrate was characterized by determining its pKa value and dissolution kinetics in water, stomach-simulated media (0.1 M HCl, pH 1.2), and mouth-simulated media (phosphate-buffered solution (PBS), pH 6.8). A solid dispersion of warfarin sodium clathrate with Kollicoat^® Smartseal 100 P or Eudragit^® E PO was prepared using hot melt extrusion (HME). The mechanical properties of extruded filaments were characterized by measuring their elastic modulus. The microparticles (1-4 mm in length) prepared with filament cut pelletizing were thermally treated to produce 'smoothened' particles, which were analyzed with optical microscopy and drug release testing. Conclusions. Microparticles with smoothened edges and an aspect ratio close to one are expected to improve mouthfeel and potentially patient compliance. No drug release was observed in mouth-simulated media, which indicated applicability to the taste masking of the microparticles. The proposed thermal treatment of HME microparticles, exemplified in this study, is a novel concept with underexplored potential in preparing taste-masked matrix pellets and dose personalization.