SOLUBILITIES AND CRYSTALLIZATION BEHAVIOR OF CIMETIDINE POLYMORPHIC FORM-A AND FORM-B

For the polymorphic forms A and B of the organic compound cimetidine, their solubilities in H2O, 2-propanol (IPA) and H2O-IPA mixture and their crystallization behavior, mainly from IPA, were studied. It became apparent that form A is more soluble than form B in any solvent and that the solubilities of both forms increase in the order H2O, IPA, H2O-IPA mixture. In IPA as a solvent, at high supersaturation ratio (S(A) greater-than-or-equal-to 3.6), form A, which is of thermodynamically metastable form, was preferentially crystallized regardless of the presence or absence (S(A) greater-than-or-equal-to 4.5) and the form of seeds (S(A) greater-than-or-equal-to 3.6). Phase transition from form A to B was not observed. The primary nucleation rate of form A was also measured at S(A) = 4.8 approximately 6.3 by the waiting-time method and surface energy sigma-A was estimated to be 8.1 x 10(-3) J.m-2. At lower supersaturation ratio (S(A) less-than-or-equal-to 2) the form corresponding to that of the seed was crystallized, contrary to results reported in earlier papers that no form B is obtained from IPA solution. The growth rate of form A was also measured at S(A) = 2.2 approximately 1.3, by the light transmittance method, and sigma-A was estimated to be 5.2 x 10(-3) J.m-2.