800 mg Darunavir tablets prepared by hot melt extrusion

Abstract

Darunavir (TMC 114) is a protease inhibitor used in the therapy of HIV-1. The aim of this study was to formulate 800 mg of Darunavir in a single unit dosage form, with suitable mechanical properties and dissolution behavior, using a corotating twin screw extruder. In preliminary investigations, extrudates of 1 mm diameter were prepared to evaluate the extrusion and dissolution behavior of Darunavir. Two different poloxamers (188 and 407) were used to modify the dissolution properties of Darunavir, and a higher solubilization for poloxamer 188 was observed. Furthermore, a zero order drug release from pure Darunavir extrudates was found which was modulated by the extrudate diameter. Extrudates of 13 mm diameter were cut into tablets containing 800 mg of Darunavir. Due to the lower specific surface area in comparison to the 1 mm extrudates, an addition of solubilizing agent was required to obtain the desired dissolution profiles. Therefore, the influence of Mannitol and poloxamer 188 was investigated in different formulations. The formulations exhibited acceptable extrusion behavior and dissolution properties.

Keywords::

• darunavir
• prezista
• hot melt extrusion
• drug release
• dissolution
• poloxamer