Celecoxib:Nicotinamide Dissociation: Using Excipients To Capture the Cocrystal's Potential

The cocrystal of celecoxib and nicotinamide (Cel:Nic) was crystallized from chloroform
in a 1:1 ratio, and the structure has been solved from powder X-ray diffraction data. The
dissolution and solubility of Cel:Nic are medium dependent and can be attributed to differences
in conversion of Cel:Nic to celecoxib polymorphs I and III (Cel-I and Cel-III). The presence of
low concentrations of surfactants facilitates the rapid conversion of neat Cel:Nic to large
aggregates of Cel-III that dissolve more slowly than commercial Cel-III into 1% SDS solution.
In contrast, combinations of Cel:Nic with both 1−10% solid SDS and PVP wet rapidly and convert
to a mixture of amorphous celecoxib and a micron-sized crystalline celecoxib form IV (Cel-IV),
which has recently been shown to be up to 4-fold more bioavailable than marketed Cel-III. More
than 90% of the suspended material dissolves within 2 min at 37 °C when transferred to 1%
SDS solution. This example highlights the importance of exploring the form conversion of
cocrystals in aqueous media prior to pharmacokinetic studies, and illustrates the potential of
simple formulations to overcome the limitations caused by rapid dissociation of cocrystals and
recrystallization of poorly soluble forms in aqueous media.
Keywords: Polymorphs; pharmaceutical; cocrystal; nicotinamide; morphology; dissolution; stability;
celecoxib; formulation