Rapid precipitation of biochemicals: Kinetics and micromixing

A grid mixer device (characteristic micromixing time ;When plotted according to the primary nucleation theory, the induction time and nucleation rate measurements for both systems exhibited a homogeneous nucleation region at high supersatuations and a heterogeneous nucleation region at low supersaturations.;The measured growth rates for both solutes over the entire range of supersaturation could be represented with a power law dependence on chemical potential driving force. The kinetic orders of crystal growth were found to be 6.7 and 2.9 for lovastatin and asparagine, respectively. These unusually high kinetic orders suggested that a different growth mechanism was controlling and was identified to be the polynuclear surface nucleation growth mechanism.;To carry out rapid precipitation on a more practical scale, use of a Two Impinging Jets (TIJ) mixer was explored in terms of its ability to deliver rapid micromixing. The two step (series-parallel) Bourne reaction scheme between 1-naphthol and diazosulfanilic acid was used to characterize the micromixing in the TIJ mixer as a function of hydrodynamics and mixer geometry. The micromixing measurements in the TIJ mixer correlated well as a function of a Damkohler number which led to a scale up criterion giving an inverse relationship between the micromixing time constant and the 1.5 power of the jet velocity.;Finally, the precipitation of lovastatin was carried out in the TIJ mixer under well mixed and poorly mixed conditions. The level of micromixing in the precipitator was found to affect the crystal size distribution (CSD) of the precipitated product when the time scale of micromixing was comparable or larger than the induction time. The CSD results also showed the usefulness of a fundamental approach that combined the kinetics information of a precipitation system and the mixing characteristics of a precipitator to explain the role of micromixing in precipitation. (Abstract shortened by UMI.)...