Crystal Growth & Design
Article
Notes
aqueous solution than those in water, 4 shows the highest
apparent solubility value of 6.0 mg/mL. In addition, the color
of the powder of 1 changed quickly from yellow to dark red in
0.1 M HCl aqueous solution, and the solubility of 1 began to
decrease gradually after 1 h. After the dissolution experiments,
the undissolved solids were filtered, and the results of XRPD
measurements indicate that the XRPD patterns of 1·HCl and
2−5 did not change, while 1 transformed to 1·HCl.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported by 973 Program of China
(2012CB821705), NSFC (20831005, 91127002, 21101173
and 21121061), and China Postdoctoral Science Foundation
(Grant No. 20110490919).
Hygroscopicity Studies. The results of hygroscopicity
experiments at 85% and 98% RH reveal that 1·H2O and 1·HCl
display serious hygroscopicity, which absorbed moisture to
almost reach the saturation within a short time (Figure 8).
However, the hygroscopicity of phenazopyridine has been
improved significantly by forming cocrystal 2 and salts 3−5
(Figure 8), indicating the stability of phenazopyridine can be
improved by forming pharmaceutical cocrystal and salts. From
the structures of 1·H2O and 2−5, it can be found that only the
pyridine nitrogen atom of phenazopyridine in 1·H2O forms an
intermolecular hydrogen bond with a water molecule, while
almost all the hydrogen bond donors (two amino groups) and
acceptor (pyridine nitrogen atom) of phenazopyridine in 2−5
form intermolecular hydrogen bonds with the coformer or
organic anions. Therefore, the phenazopyridine in 1·H2O can
still interact with water molecules by forming hydrogen bonds
with two amino groups of phenazopyridine, while the water
molecules are hard to further interact with phenazopyridine in
2−5, as almost all the hydrogen bond sites in phenazopyridine
form hydrogen bonds with coformer or organic anions.
Accordingly, 1·H2O and 1·HCl are much more prone to hygro-
scopic compared with 2−5.
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CONCLUSIONS
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One monohydrate, one cocrystal, and three salts of
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S
* Supporting Information
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AUTHOR INFORMATION
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Corresponding Author
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dx.doi.org/10.1021/cg300327x | Cryst. Growth Des. 2012, 12, 3144−3152