Crystallization Behavior and Transformation Kinetics of L-Histidine Polymorphs

Abstract

The crystallization and transformation behavior of the polymorphs of L-histidine (A,B) and the transformation kinetics were investigated in aqueous solutions. Both polymorphs precipitate in almost the same ratio from solutions in a wide concentration range. The ratio of the polymorphs in the precipitate was scarcely influenced by temperature, unlike the behavior of L-glutamic acid. Transformation from B to A with a solution-mediated transformation mechanism occurred. The activation energy for the overall transformation was estimated as about 38 kj/mol. From measurements of the solubilities at temperatures between 283 and 333 K, it was confirmed that A is a stable and B a metastable form. From a van’t Hoff plot the heat of fusion of L-histidine polymorphs was obtained as 15 kj/mol, which is about half that of L-glutamic acid. No seed effect of either A or B crystals on the precipitation behavior was observed. A kinetic study of the transformation process was carried out and both the rate constants of growth of A(kG) and dissolution of B crystals(kp) were estimated simultaneously. At 313 K kDwas nearly six times larger than kG, indicating that the transformation process is growth-controlled. © 1993, The Society of Chemical Engineers, Japan. All rights reserved.