Anion-switchable supramolecular gels for controlling pharmaceutical crystal growth.
We describe the use of low-molecular-weight supramolecular gels as media for the growth of molecular crystals. Growth of a range of crystals of organic compounds, including pharmaceuticals, was achieved in bis(urea) gels. Low-molecular-weight supramolecular gelators allow access to an unlimited range of solvent systems, in contrast to conventional aqueous gels such as gelatin and agarose. A detailed study of carbamazepine crystal growth in four different bis(urea) gelators, including a metallogelator, is reported. The crystallization of a range of other drug substances, namely sparfloxacin, piroxicam, theophylline, caffeine, ibuprofen, acetaminophen (paracetamol), sulindac and indomethacin, was also achieved in supramolecular gel media without co-crystal formation. In many cases, crystals can be conveniently recovered from the gels by using supramolecular anion-triggered gel dissolution; however, crystals of substances that themselves bind to anions are dissolved by them. Overall, supramolecular gel-phase crystallization offers an extremely versatile new tool in pharmaceutical polymorph screening.
Department of Chemistry, Durham University, South Road, Durham DH1 3LE, UK.
Jonathan A
JA
Foster
Marc-Oliver M
MO
Piepenbrock
Gareth O
GO
Lloyd
Nigel
N
Clarke
Judith A K
JA
Howard
Jonathan W
JW
Steed
D000838:Anions / Q000737:chemistry*; D002220:Carbamazepine / Q000737:chemistry; D003460:Crystallization; D005780:Gelatin / Q000737:chemistry; D005782:Gels / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012685:Sepharose / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
D000838:Anions; D005782:Gels; D004364:Pharmaceutical Preparations; D012997:Solvents; D002220:Carbamazepine; D005780:Gelatin; D012685:Sepharose