The cocrystal of celecoxi
b and nicotinamide (
Cel:Nic) was crystallized from chloroformin a 1:1 ratio, and the structure has
been solved from powder X-ray diffraction data. Thedissolution and solu
bility of
Cel:Nic are medium dependent and can
be attri
buted to differencesin conversion of
Cel:Nic to celecoxi
b polymorphs I and III (
Cel-I and
Cel-III). The presence oflow concentrations of surfactants facilitates the rapid conversion of neat
Cel:Nic to largeaggregates of
Cel-III that dissolve more slowly than commercial
Cel-III into 1% SDS solution.In contrast, com
binations of
Cel:Nic with
both 1-10% solid SDS and PVP wet rapidly and convertto a mixture of amorphous celecoxi
b and a micron-sized crystalline celecoxi
b form IV (
Cel-IV),which has recently
been shown to
be up to 4-fold more
bioavaila
ble than marketed
Cel-III. Morethan 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 ofcocrystals in aqueous media prior to pharmacokinetic studies, and illustrates the potential ofsimple formulations to overcome the limitations caused
by rapid dissociation of cocrystals andrecrystallization of poorly solu
ble forms in aqueous media.