2732 Crystal Growth & Design, Vol. 10, No. 6, 2010
Vogt et al.
Conclusions
for assistance with water content determinations. Professor
ꢀ
Gerard Coquerel (University of Rouen) and Dr. Ludovic
Renou (Pharmorphix) are thanked for insightful discussions.
Racemic carvedilol phosphate (I) was found to exist as a
solid solution of its enantiomers, which is a relatively infre-
quent occurrence in organic molecular crystals. Efforts to
solve its crystal structure were hindered by weakly diffracting
twinned crystals, from which data refinement was difficult.
Multinuclear solid-state NMR analysis showed indications of
disorder in the vicinity of the chiral center. Single enantiomer
phosphate salts were therefore prepared and found to be
isomorphic with the racemate using SSNMR and other
techniques but lacking the disorder element detected in the
SSNMR spectra of the racemate. A crystal of I-(R) did not
exhibit twinning and yielded good diffraction data that were
readily solved with an R1 of <5%. The structure of the single
enantiomer enabled a better understanding of the related
racemic crystal structure. It is unusual for the single-enantiomer
and racemic crystals of a compound to have such similar unit
cell dimensions and crystallize as isomorphous phases, allowing
for formation of a solid solution. That the racemate yields
twinned crystals, whereas the enantiopure form does not even
though the metric requirements for twinning are met, is also
worthy of note. It may be possible that the development of twin
domains in this system depends on the presence of both
enantiomers; however, this cannot be confirmed at the present
time. The increased disorder seen by SSNMR in I is associated
with the formation of the solid solution, as confirmed by
thermal analysis.
Supporting Information Available: A movie file illustrating the
rehydration process for a single crystal of I-(R), crystallo-
graphic information files for the crystal structures of I and
I-(R), and additional PXRD, NMR, and SSNMR data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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2
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ꢀ
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Acknowledgment. The authors thank Dr. Leo Hsu
(GlaxoSmithKline) for performing the chiral preparative
chromatographic separation of racemic carvedilol and Pro-
fessor Judith Howard (University of Durham), in whose
laboratories one of us (O.V.C.) prepared the crystals of I.
The authors alsothankMr. Jerome Socha (GlaxoSmithKline)
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