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.