Toward Understanding the Growth of Cefradine in Aqueous Solution

Crystal growth, which is one of the fundamental steps in the crystallization process, can affect the morphology of crystals which will further affect physicochemical properties of products and downstream processing. In this study, crystal growth of cefradine in aqueous solution was systematically investigated by combining experimental methods and molecular dynamics simulations. Single crystal growth experiments were adopted to obtain the growth kinetics data of cefradine in water. Growth kinetics models considering the bulk diffusion step and surface integration step were applied to evaluate the experimental data. Surface chemistry, Connolly surface, radial distribution function, and electrostatic potential were calculated through molecular dynamics simulation to further explore the growth kinetics from the molecular level. The results revealed that water molecules preferred to be adsorbed onto the (1 0 1) crystal face than the (0 1 1) and (0 1̅ 1) surfaces due to the favored hydrophilicity and solvent adsorption sites. In addition, the stronger interaction between water molecules and the (1 0 1) crystal face by electrostatic and hydrogen-bonding interactions would further highly hinder the crystal growth along the radial direction. Finally, a possible growth mechanism based on blocking effect of solvent molecules was proposed to interpret the different growth kinetics along the axial and radial directions.