The liquid-solid mixing characteristics predict reduced values for the energy of collision, frequency of collisions and characteristic time between two strong collisions when scaling up on a tip-speed basis. This would predict the expected decrease in secondary nucleation.

A summary of definitions for the predicted parameters is as follows:

1. Maximum value of energy dissipation -- microscale phenomena -- energy dissipation behind the agitator blades -- controls breakage, nucleation and micromixing in this zone.

2. Local values of energy dissipation -- microscale phenomena -- average energy dissipation plus energy dissipation in bulk slurry and at baffle -- controls breakage, nucleation and micromixing in these zones.

3. Characteristic time of micromixing -- time of microscale degradation of non-homogeneous concentrations -- important for precipitations.

4. Shear rates -- characteristic shear rate at the microscale level --scaleup governs mass transport process for growing and dissolving solids.

5. Maximum energy of collisions at zone of maximum turbulence near impeller blades -- collisional energy of particles -- higher values increase breakage and secondary nucleation.

6. Energy of collisions in bulk -- collisional energy of particles -- although less than the maximum value, the large number of collisions in the bulk can affect breakage and secondary nucleation.

7. Frequency of collisions of maximum energy -- predicts how often the slurry particles see the maximum collisional energy -- if higher, more breakage and secondary nucleation.

8. Time between two strong collisions -- average period of uninterrupted crystal growth.

New developments

A number of new developments, some genuine innovations and others, improvements to existing technologies, show promise or are being utilized for crystallization.

Sonocrystallization

This technique involves the use of ultrasonics to influence crystallizations. Ultrasound can impact both nucleation and growth and can be used to induce nucleation in the metastable zone without seeding, avoiding primary nucleation.

Ultrasound can also be used to generate secondary nuclei via the impact of the large forces originating from the collapse of cavitation bubbles on or near the crystal surfaces. The technology can influence growth by enhancing mass transfer near the crystal surface. Crystal purity may improve, as crystal surface impurities are preferentially dissolved in the temporary local undersaturated solution, resulting from highly localized heating from cavitation near the crystal surfaces.

It may be possible to dictate the polymorph that is crystallized via this technology, by controlling the supersaturation at the point of nucleation. Commercial units typically operate at around 20 kHz with multiple transducers, each with relatively low power output (approximately 0.1-1.0 W/cm² at the point of delivery) coupled to the wall of the crystallizer. Average power densities for the mutliple transducers are in the 75-80 W/L range.

CFD

Computational fluid dynamics (CFD) shows some promise in modeling fluid and solids behavior in crystallizers and precipitators. This includes modeling mixing in precipitators and crystal suspension in a crystallizer where fines destruction is employed to modify the CSD. This methodology is still under development.

Measurement techniques

FTIR is frequently used to measure solution concentrations of active ingredient. In addition, Lasentec's Focused Beam Reflectance Measurement (FBRM) and Particle Vision Measurement (PVM) can be utilized to monitor crystallizations and precipitations. The former provides a way to detect the point of nucleation and estimate the growth rate by measuring the change of particle count and dimensions. The latter can provide continuous video microscopy of the particles, including their shape. Raman spectroscopy can be utilized with these instruments in order to detect solid properties, including different forms such as polymorphs.

Wayne Genck, principal of Genck International, is an industrial consultant in the field of crystallization and precipitation. He can be reached at (708)748-7200.