Crystal Growth of Salicylamide in Organic Solvents

Abstract

Salicylamide was used as a model active pharmaceutical compound to investigate the crystal growth process and its associated kinetics. The impact of organic solvent, supersaturation, and temperature on the crystal growth was studied. The multiparticle crystal growth kinetics were determined using the seeded isothermal de-supersaturation method and modeled using several growth rate equations, using different representations of the driving force. The results showed that crystal growth is significantly influenced by experimental conditions. Within the range of experimental conditions, the growth kinetics was affected strongly by the temperature and to a lesser degree by solvent choice. Comparison of the growth order parameter reveals a surface integration controlled growth. Higher than expected activation energies indicate desolvation as a governing process. A comparison of the influence of the solvent on the crystal growth of salicylamide against previously published approximate data at much higher supersaturation shows good agreement, but the influence on the interfacial energy is opposite to that observed for crystal nucleation. In a detailed comparison with crystal growth data of salicylic acid, there is a consistency in the influence of the solvent on the crystal growth of the two compounds. Salicylamide growth kinetics is more strongly affected by increasing temperature than salicylic acid.