Crystal Growth Kinetics of Pharmaceutical Compounds

The crystal growth kinetics of piracetam, fenofibrate, phenylbutazone, acetaminophen, carbamazepine, and risperidone in methanol have been studied by two different methods; the isothermal seeded desupersaturation experiment (ISD) and the rotating disk technique (RD). Data has been collected in the range of temperature 288-303 K and at different supersaturations for the ISD experiments. The RD experiments were performed at constant supersaturation. In the ISD experiments, principal component analysis has been used to relate solution concentrations from IR measurements. An empirical power law equation has been fitted to the experimental desupersaturation data, and parameter values suggest surface integration control for all the APIs studied, a conclusion further supported by a separate mass transfer analysis. The order of rate of growth among the compounds and the magnitude of the growth rates determined by the two methods are in good agreement. In addition, the Burton Cabrera Frank (BCF) and Birth and Spread (B+S) surface integration models have been fitted to the ISD desupersaturation data, and average solid-liquid interfacial energies, mean diffusion distances, and surface mass transport rates have been estimated. An analysis of the experimental results and the growth rate parameters is performed to examine to what extent the difference in growth rate of different compounds can be rationalized.