This work describes the use of clavulanic acid (CA) precipitation as the final step in the process of purification of CA from fermentation broth as an alternative to conventional methods employed traditionally. The purpose of this study was to use a stable intermediate (t-octylamine) between the conversion of CA to its salt form (potassium clavulanate), thereby enabling the resulting intermediate (amine salt of clavulanic acid) to improve the purification process and maintain the stability of the resulting potassium clavulanate. To this end, response surface methodology was employed to optimize the precipitation step. For the first reaction, five temperatures (6.6 to 23.4 ºC), concentrations of clavulanic acid in organic solvent (6.6 to 23.4 mg/mL) and t-octylamine inflow rates (0.33 to 1.17 drop/min) were selected based on a central composite rotatable design (CCRD). For the second reaction, five temperatures (11.6 to 28.4 ºC), concentrations of clavulanic acid amine salt in organic solvent (8.2 to 41.8 mg/mL) and concentrations of potassium 2-ethylhexanoate (0.2 to 1.2 molar) were also selected using CCRD. From these results, precipitation conditions were selected and applied to the purification of CA from the fermentation broth, obtaining a yield of 72.37%.

Fluid dynamics simulations were applied for evaluating the suspension of particles in stirred vessels. The spatial distribution of particles throughout the vessel was characterized by a single parameter, here called the suspension quality (s). Based on simulation results, a semi-empirical correlation was developed that correlated the suspension quality with the vessel geometry and solid and fluid properties, including a large variety of conditions, such as vessel and impeller diameters, impeller clearances, rotational speeds, particle densities and sizes. Comparison of the model with experimental data from the literature (Bohnet and Niesmak, 1980) suggests that the model can be extended to systems with different impeller geometries by adjustment of one single empirical parameter. The model can be used in the design of stirred vessels for the identification of the rotation speeds necessary to promote a specified suspension quality.

Crystallization and precipitation from solutions are responsible for 70% of all solid materials produced by the chemical industry. Competing with distillation as a separation and purification technique, their use is widespread. They operate at low temperatures with low energy consumption and yield with high purifications in one single step. Operational conditions largely determine product quality in terms of purity, filterability, flowability and reactivity. Producing a material with the desired quality often requires a sound knowledge of the elementary steps involved in the process: creation of supersaturation, nucleation, crystal growth, aggregation and other secondary processes. Mathematical models coupling these elementary processes to all particles in a crystallizer have been developed to design and optimize crystallizer operation. For precipitation, the spatial distribution of reactants and particles in the reactor is important; thus the tools of computational fluid dynamics are becoming increasingly important. For crystallization of organic chemicals, where incorporation of impurities and crystal shape are critical, molecular modeling has recently appeared as a useful tool. These theoretical developments must be coupled to experimental data specific to each material. Theories and experimental techniques of industrial crystallization and precipitation from solutions are reviewed, and recent developments are highlighted.

The effect of magnetic field on the crystallization of diamagnetic zinc sulfate was investigated in a series of controlled batch cooling experiments. Zinc sulfate solutions were exposed to magnetic fields of different intensities, up to a maximum of 0.7T. A clear influence of magnetic field on the following zinc sulfate crystallization parameters was found: an increase in saturation temperature, a decrease in metastable zone width, and an increase in growth rate and average crystal size. These effects were observed for the diamagnetic zinc sulfate, but not in similar, previously reported experiments for paramagnetic copper sulfate.

Crystallization from solutions was applied to produce stoichiometric and crystalline hydroxyapatite (HAP) suitable for use as a biomaterial. This was accomplished by keeping a low supersaturation through the following procedure: semi-continuous operating mode, slow reactant addition rate and addition of a calcium complexing agent. A high temperature (90 °C) and probably carbonate incorporation also favored the formation of a well crystallized material. A qualitative correlation was found between the supersaturation and HAP properties such as crystallinity and particle size.