Crystal polymorphism of pharmaceuticals: probing crystal nucleation at the molecular level.
Paracetamol, sulfathiazole and L-glutamic acid are presented as examples of pharmaceutical crystal polymorphic systems. The effect of N-acylated sulfathiazole derivatives (3-6) on sulfathiazole crystallisation is discussed, and possible modes of action presented. Methods for the control of the crystal polymorphism of L-glutamic acid which utilise the principles of conformation mimicry and co-operative binding are presented. The preparation of a series of bis-amides of EDTA derived from sulfathiazole, 5-aminoisophthalic acid and 4-hydroxyaniline (i.e. compounds 9a-c) is presented, as is data on the effect of these compounds on the crystallisation of, respectively, sulfathiazole, L-glutamic acid and paracetamol.
Analytical and Biological Chemistry Research Facility, School of Pharmacy, University College Cork, College Road, Cork, Ireland.
Kevin P
KP
Guiry
Joanne M
JM
Kelleher
Simon E
SE
Lawrence
Marie T
MT
McAuliffe
Humphrey A
HA
Moynihan
Andrea L
AL
Ryan
D000082:Acetaminophen / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry*; D015394:Molecular Structure; D000077589:Sulfathiazole; D013432:Sulfathiazoles / Q000737:chemistry*
D013432:Sulfathiazoles; D000082:Acetaminophen; D018698:Glutamic Acid; D004492:Edetic Acid; D000077589:Sulfathiazole