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New form discovery for the analgesics flurbiprofen and sulindac facilitated by polymer-induced heteronucleation
Authors
Adam J. Matzger
Adam L. Grzesiak
+28 more
Bernstein
Bonafede
Bondi
Brittain
Burger
Byrn
Chyall
Flippen
Grzesiak
Grzesiak
Ha
Henck
Hilden
Hiremath
Koo
Lacoulonche
Lacoulonche
Lang
Lee
Mitchell
Plakogiannis
Price
Price
Price
Rodríguez‐Spong
Tros de Ilarduya
Weissbuch
Zaccaro
Publication date
1 November 2007
Publisher
'Wiley'
Doi
Cite
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on
PubMed
Abstract
The selection and discovery of new crystalline forms is a longstanding issue in solid-state chemistry of critical importance because of the effect molecular packing arrangement exerts on materials properties. Polymer-induced heteronucleation has recently been developed as a powerful approach to discover and control the production of crystal modifications based on the insoluble polymer heteronucleant added to the crystallization solution. The selective nucleation and discovery of new crystal forms of the well-studied pharmaceuticals flurbiprofen (FBP) and sulindac (SUL) has been achieved utilizing this approach. For the first time, FBP form III was produced in bulk quantities and its crystal structure was also determined. Furthermore, a novel 3:2 FBP:H 2 O phase was discovered that nucleates selectively from only a few polymers. Crystallization of SUL in the presence of insoluble polymers facilitated the growth of form I single crystals suitable for structure determination. Additionally, a new SUL polymorph (form IV) was discovered by this method. The crystal forms of FBP and SUL are characterized by Raman and FTIR spectroscopies, X-ray diffraction, and differential scanning calorimetry. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2978–2986, 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57336/1/20954_ftp.pd
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