Characterization of a novel polymorphic form of celecoxib.

ABSTRACT

A new solid form (Form IV) of celecoxib was prepared in the presence of Polysorbate 80 and HPMC. A celecoxib suspension containing the Form IV had significantly higher bioavailability (>4 times) in dogs than the marketed capsules and the suspension containing bulk drug powders (Form III). The new form was characterized using differential scanning calorimetry, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), infrared spectroscopy, and Raman spectroscopy. The solids separated from the suspension containing the new form showed a melt onset at 145-148 degrees C, which was about 12-15 degrees less than known melting points of Form I, II ,and III of celecoxib. The PXRD pattern of the separated solids was not consistent with any of the known celecoxib crystal forms or the known excipients in the suspension. The formation of the new solid form (Form IV) was dependent upon the concentration and ratio of HPMC and Polysorbate 80. A faster dissolution rate (>2 times) of Form IV was observed compared to the thermodynamically stable form of celecoxib (Form III). There were no measurable changes in the solid state of Form IV either in dried solids or in the suspension for at least 6 months at 40 degrees C and 16 months at 25 degrees C.