Ultrasound assisted crystallization or sonocrystallization relies on the power ultrasound (20–100 kHz) and extended sonochemistry (100 kHz – 2 MHz) bands of the acoustic frequency range in order to produce cavitation. For reference human hearing responds to frequencies between 20 Hz–19 kHz. The energy release associated with cavity collapse can lead to prolific sono-nucleation and crystallization.

Cavitation microbubbles arise when the expanding pressure wave finds structural defects, such as foreign matter, particles, dust and dissolved gas. On the compression phase of the acoustic pressure wave they collapse violently to generate regions of extreme excitation, temperature (nearly 5,000°C) and pressure (2,000 bar).

Powerful sono-nucleation effects can be applied to primary API product manufacture and in effect our equipment can be an easy retro-fit to existing batch reactors, as shown for DISCUS and crystallizers whether by cooling or antisolvent crystallization.

Sonocrystallization processes can add significant value-added benefits and are capitalised through new process patents that can be created for individual products, thus securing and extending marketing timescales. Sonocrystallization can be applied in secondary manufacture of pharmaceutical ingredients and lends itself to polymorphic systems. By controlling nucleation, we can take control of, and improve, crystal size distribution, morphology, impurities, polymorphism, bulk density and solid-liquid separation. Ultrasound can also induce secondary nucleation by mechanically disrupting crystals or loosely bound agglomerates.

An attractive business feature of the Prosonix sonocrystallization technology is that it can be applied at ANY STAGE in a pharmaceutical product pipeline from discovery through to process optimisation / manufacture and formulation / drug delivery. The technique can be used in early laboratory studies through to full industrialization. This scale-out feature of the technology ensures that success in the lab can be replicated across scale.

Almost all chemical processes utilise at least one crystallization step, either as the key separation mechanism or final polish filtration. Crystallization has been described as one of the most difficult unit operations to control, irrespective of whether the process utilises cooling, evaporative, anti-solvent or pH shift.

Prosonix has developed a suite of proprietary sonocrystallization technologies and equipment which use power ultrasound to control the crystallization process and allow the precise production of high purity organic and inorganic microcrystalline chemicals - be they intermediates, excipients, API's, binders, sugars or colorants.

The technology is available for use on a commercial scale and is already validated across scale in cGMP environments.

Prosonix sonocrystallization technology can be used in in-line continuous flow mode, or batch mode for in-situ generation of seed crystals using the process liquid itself as the source for the seeds, thus overcoming one of the major limitations of classical seeded processes.

Please see the attachment below in order to access a useful paper from the Journal of Process Research and Development, authored by Graham Ruecroft and David Hipkiss:

This technology is available through partnership and licensing from Prosonix.

Attachments:

File	File size
OPRD_Sonocrystallization.pdf	903 Kb