title: Controlling pharmaceutical crystallization with designed polymeric heteronuclei.
abstract: To investigate the hypothesis that molecules acting as crystallization inhibitors in solution could be transformed into crystallization promoters, additives were synthesized that mimic the pharmaceuticals acetaminophen and mefenamic acid and also possess polymerizable functionality. It was found that, in solution, these additives face-selectively inhibit crystal growth and lead to overall slower crystal appearance. In contrast, when the tailor-made additives were incorporated into an insoluble polymer, the induction time for the onset of crystal formation for both pharmaceuticals was substantially decreased. This approach now allows for the synthesis of tailor-made polymers that decrease the induction time for crystal appearance and may find application in compounds that are resistant to crystallization or in improving the fidelity of heteronucleation approaches to solid form discovery.
authors.affiliation: Department of Chemistry and the Macromolecular Science and Engineering Program, The University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Laura Y
authors.initials: LY
authors.lastname: Pfund
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Price
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Frick
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Matzger
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D008528:Mefenamic Acid / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D011108:Polymers; D000082:Acetaminophen; D008528:Mefenamic Acid