Hydrodynamic cavitation crystallization device and process

Abstract

A device and process for crystallizing a compound using hydrodynamic cavitation comprising the steps of mixing at least one stream of a solution of such compound to be crystallized with at least one stream of an anti-solvent and passing the mixed streams at an elevated pressure through a local constriction of flow to create hydrodynamic cavitation thereby causing nucleation and the direct production of crystals.

Description

BACKGROUND OF THE INVENTION [0001] The present invention relates to a device and process for crystallizing compounds using hydrodynamic cavitation. The types of compounds that may be crystallized include pharmaceutical compounds as well as any other compounds used in industry. [0002] Crystallization from solution of pharmaceutically active compounds or their intermediates is the typical method of purification used in industry. The integrity of the crystal structure, or crystal habit, that is produced and the particle size of the end product are important considerations in the crystallization process. [0003] High bioavailability and short dissolution time are desirable or often necessary attributes of the pharmaceutical end product. However, the direct crystallization of small sized, high surface area particles is usually accomplished in a high supersaturation environment which often results in material of low purity, high friability, and decreased stability due to poor crystal struc...

AI Technical Summary

Benefits of technology

The present invention relates to a device and process for crystallizing compounds using hydrodynamic cavitation. This technology can produce small, stable crystals with high purity and high bioavailability, without the need for high energy milling. The device and process can create and control hydrodynamic cavitation, which involves the formation of bubbles and cavities within a liquid stream resulting from a localized pressure drop in the liquid flow. The resulting crystals have a high surface area, high chemical purity, and high stability. The invention can be used for direct small particle crystallization of pharmaceutical compounds, and can improve particle size and stability while increasing bioavailability.

Problems solved by technology

However, the direct crystallization of small sized, high surface area particles is usually accomplished in a high supersaturation environment which often results in material of low purity, high friability, and decreased stability due to poor crystal structure formation.

Slow crystallization is a common technique used to increase product purity and produce a more stable crystal structure, but it is a process that decreases crystallizer productivity and produces large, low surface area particles that require subsequent high intensity milling.

However, high energy milling has drawbacks.

Milling may result in yield loss, noise and dusting, as well as unwanted personnel exposure to highly potent pharmaceutical compounds.

Also, stresses generated on crystal surfaces during milling can adversely affect labile compounds.

Overall, the three most desirable end-product goals of high surface area, high chemical purity, and high stability cannot be optimized simultaneously using current crystallization technology without high energy milling.

When using current reverse addition technology for direct small particle crystallization, a concentration gradient can not be avoided during initial crystal formation because the introduction of feed solution to anti-solvent in the stirred vessel does not afford a thorough mixing of the two fluids prior to crystal formation.

The existence of concentration gradients, and therefore a heterogeneous fluid environment at the point of initial crystal formation, impedes optimum crystal structure formation and increases impurity entrainment.

Another standard crystallization procedure employs temperature variation of a solution of the material to be crystallized in order to bring the solution to its supersaturation point, but this is a slow process that produces large crystals.

Also, despite the elimination of a solvent gradient with this procedure, the resulting crystal characteristics of size, purity and stability are difficult to control and are inconsistent from batch to batch.

On the other hand, crystallization procedures using hydrodynamic cavitation have not yet been proposed.

As the pressure of the liquid then increases, vapor condensation takes place in the cavities and bubbles, and they collapse, creating very large pressure impulses and very high temperatures.

Images