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.