SOLVENT EFFECT OF ETHANOL ON CRYSTALLIZATION AND GROWTH-PROCESS OF L-HISTIDINE POLYMORPHS

The solvent effect of ethanol on precipitation behavior and crystal growth rates of the A and B polymorphs of L-histidine were investigated in aqueous solutions. The fraction of A in precipitates decreases quickly when the volume fraction of ethanol in solvent (VOL) increases above 0.2, and finally pure B is obtained at 0.4 VOL. The transformation rate from B to A decreases with ethanol concentration. The growth rate of B was larger than that of A at the same supersaturation degree in both aqueous and ethanol solutions. However, the growth rates of both polymorphs are almost the same at the same concentration in aqueous solution, corresponding to the precipitation behaviors. In ethanol solutions, the growth rate of B is slightly larger than that of A at the same concentration of 0.2 VOL. However, the growth rate of B is much larger than A at 0.4 VOL. The results indicate that the precipitation behavior is controlled mainly by the relative growth rates of the polymorphs. The change of the growth mechanism with increasing VOL is suggested. The concentration decrease of the conformer which corresponds to A is suggested as responsible for the solvent effect.