1991 Volume 24 Issue 2 Pages 237-242
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 (SA ≥ 3.6), form A, which is of thermodynamically metastable form, was preferentially crystallized regardless of the presence or absence (SA ≥ 4.5) and the form of seeds (SA ≥ 3.6). Phase transition from form A to B was not observed. The primary nucleation rate of form A was also measured at SA = 4.8–6.3 by the waiting-time method and surface energy σA was estimated to be 8.1 × 10–3 J·m–2. At lower supersaturation ratio (SA ≤ 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 SA = 2.2–1.3, by the light transmittance method, and σA was estimated to be 5.2 × 10–3 J·m–2.
