Methods and apparatus for particle formation

Abstract

The invention provides a method for forming particles of a target substance (26), involving: (a) preparing a solution or suspension of the substance in a vehicle (21) which is or includes either a near-critical fluid (21) or a first supercritical fluid; (b) introducing the solution or suspension into a particle formation vessel (32); and (c) contacting the solution or suspension, in the particle formation vessel, with a second supercritical fluid, under conditions which allow the second supercritical fluid to cause precipitation of particles of the target substance from the solution or suspension; wherein the second supercritical fluid is miscible or substantially miscible with the vehicle and is a fluid in which the target substance is insoluble or substantially insoluble. Also provided is apparatus for use in carrying out an embodiment of the method, including a particle formation vessel and means for controlling the temperature and pressure inside it; a fluid mixing vessel and means for controlling the temperature and pressure inside it; first fluid inlet means for introducing into the fluid mixing vessel a vehicle and a solution of a target substance in a primary solvent, so as to form in the fluid mixing vessel a solution of the substance and the primary solvent in the vehicle; and second fluid inlet means for introducing the solution thus formed, preferably together with a second supercritical fluid, into the particle formation vessel. The invention also provides a particulate product formed using the method.

Description

[0001] This invention relates to the controlled formation of particulate products using supercritical fluids. It provides methods and apparatus for the formation of substances in particulate form, and also particulate products of the methods.BACKGROUND TO THE INVENTION[0002] It is known to form particles of a substance of interest (a "target substance") by dissolving or suspending it in a suitable vehicle and then using a supercritical fluid anti-solvent to extract the vehicle to cause particle precipitation.[0003] One particular technique for doing this is known as "SEDS" (Solution Enhanced Dispersion by Supercritical fluids). This is described in WO-95 / 01221 and (in a modified form) in WO-96 / 00610, The essence of SEDS is that a solution or suspension of a target substance, in an appropriate vehicle, is co-introduced into a particle formation vessel with a supercritical fluid anti-solvent having a relatively high flow rate, in such a way that two things happen substantially simulta...

AI Technical Summary

Benefits of technology

[0018] Using the method of the invention, particles can be formed even of substances which are soluble in a chosen supercritical fluid, by using that supercritical fluid as the vehicle for the substance, and making use of another supercritical fluid (the second supercritical fluid) as the anti-solvent to cause particle precipitation. The target substance is able to dissolve or be suspended in the vehicle, but to precipitate out of it when the vehicle and the second supercritical fluid mix, without product loss into the second supercritical fluid.

[0093] The following examples demonstrate how the method of the present invention may be used to produce a range of target materials, some of which would be incompatible with a conventional SEDS process, whilst allowing a high degree of control over the product properties.

Problems solved by technology

Processes such as SEDS are not however suitable for all types of target substance.

This can lead to reduced product yield, not to mention engineering problems when the solute later precipitates out of the supercritical fluid outside the particle formation vessel.

If the substance is at all soluble in the supercritical fluid, whether simply because of the chemical natures of the substance and the fluid (which may also contain modifiers), or because of the particular operating conditions (such as temperature and pressure) being used, problems can arise.

Such techniques are thus restricted in application to substances which are poorly soluble or completely insoluble in the chosen supercritical fluid.

For this particular supercritical fluid, it is generally non-polar or low polarity substances which cause problems, being either very or at least reasonably soluble in it.

Thus, for instance, low molecular weight lipophilic materials cannot easily be formed into particles using supercritical carbon dioxide.

In the past, such problems have been overcome either by altering the operating conditions to reduce solubility of the target substance in the supercritical fluid (it is not always possible, however, to alter the conditions sufficiently to achieve that), or by using a different technique altogether for particle formation.

However, RESS is generally a less accurate and reliable technique than techniques such as SEDS, allowing less control over the characteristics of the particles formed.

Alternatively, one might attempt to use a different supercritical fluid as the anti-solvent, but it can often be very difficult to select a supercritical fluid which is not only an anti-solvent for the target substance but also capable of dissolving the solvent vehicle-both requirements need to be met for the fluid to be useable.

Supercritical nitrogen, for instance, would act as an anti-solvent for the low molecular weight lipophilic materials which cannot be processed using supercritical carbon dioxide, but most conventional organic solvents are insoluble in supercritical nitrogen, so the choice of vehicle would be extremely limited.

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