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Title: Celecoxib: Nicotinamide Dissociateion: Using Excipients to Capture the Cocrystal's Potential

Abstract

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.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
929916
Report Number(s):
BNL-80505-2008-JA
TRN: US200822%%936
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Molecular Pharmaceutics; Journal Volume: 4; Journal Issue: 3
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DRUGS; DISSOCIATION; DISSOLUTION; MIXTURES; NICOTINAMIDE; RECRYSTALLIZATION; SOLUBILITY; BIOLOGICAL AVAILABILITY; national synchrotron light source

Citation Formats

Remenar,J., Peterson, M., Stephens, P., Zhang, Z., Zimenkov, Y., and Hickey, M. Celecoxib: Nicotinamide Dissociateion: Using Excipients to Capture the Cocrystal's Potential. United States: N. p., 2007. Web. doi:10.1021/mp0700108.
Remenar,J., Peterson, M., Stephens, P., Zhang, Z., Zimenkov, Y., & Hickey, M. Celecoxib: Nicotinamide Dissociateion: Using Excipients to Capture the Cocrystal's Potential. United States. doi:10.1021/mp0700108.
Remenar,J., Peterson, M., Stephens, P., Zhang, Z., Zimenkov, Y., and Hickey, M. Mon . "Celecoxib: Nicotinamide Dissociateion: Using Excipients to Capture the Cocrystal's Potential". United States. doi:10.1021/mp0700108.
@article{osti_929916,
title = {Celecoxib: Nicotinamide Dissociateion: Using Excipients to Capture the Cocrystal's Potential},
author = {Remenar,J. and Peterson, M. and Stephens, P. and Zhang, Z. and Zimenkov, Y. and Hickey, M.},
abstractNote = {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.},
doi = {10.1021/mp0700108},
journal = {Molecular Pharmaceutics},
number = 3,
volume = 4,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}