Crystal Growth Kinetics of Theophylline Monohydrate

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Abstract
The crystal growth kinetics of theophylline monohydrate from aqueous buffered supersaturated solutions were investigated at 10, 20, 30, and 40°C. Crystallization experiments were carried out isothermally at pH 6. During growth the crystal count and size distributions were monitored in situ. The growth rate was evaluated from the rate of change of the size with time at a constant value of the size distribution. The growth rate is independent of the stirring rate and the activation energy for growth is higher than the value for simple diffusion, 14.3 and 4.4 kcal/mol, respectively. This indicates that crystal growth of theophylline monohydrate is controlled by a surface reaction mechanism rather than by solute diffusion in the bulk. The growth-rate dependence on the supersaturation was compared with crystal growth theories. The data are described by the screw dislocation model and by the parabolic law, suggesting a defect-mediated growth mechanism rather than a surface nucleation mechanism.