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 degrees 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.
Remenar
Julius F
JF
TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, Lexington, Massachusetts 02421, and Department of Physics & Astronomy, Stony Brook University, Stony Brook, New York 11794-3800, USA. JRemenar@tpius.jnj.com
Peterson
Matthew L
ML
Stephens
Peter W
PW
Zhang
Zhong
Z
Zimenkov
Yuri
Y
Hickey
Magali B
MB
D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D005079:Excipients; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009536:Niacinamide / Q000737:chemistry*; D033362:Powder Diffraction; D011720:Pyrazoles / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013449:Sulfonamides / Q000737:chemistry*; D013501:Surface-Active Agents
D005079:Excipients; D011720:Pyrazoles; D013449:Sulfonamides; D013501:Surface-Active Agents; D009536:Niacinamide; D000068579:Celecoxib