Patent ID: 7108867

Claim:
A process for the preparation of uniform particles of a pharmacologically-active substance, said particles having a mass median diameter of less than 10 microns, the process comprising the steps of: (a) preparing a first liquid comprising water, the pharmacologically-active substance and a modulator selected from the group consisting of trialkyl esters of citric acid, wherein the modulator has a solubility in water which decreases with increasing temperature; (b) contacting the first liquid with a second liquid comprising an anti-solvent supercritical fluid and an organic solvent using a supercritical anti-solvent technique selected from the group consisting of GAS, SEDS, and SAS; wherein: i) the pharmacologically-active substance is soluble in water; ii) the weight ratio of the modulator to the pharmacologically-active substance present in the first liquid is in the range of from 50:1 to 1:200; iii) the organic solvent is soluble in the anti-solvent supercritical fluid; iv) the pharmacologically-active substance is substantially insoluble in the second liquid; v) the amount of organic solvent used is less than that required to saturate the anti-solvent supercritical fluid and vi) the temperature of the first liquid is at or above the cloud point temperature of the first liquid when the first liquid contacts the second liquid; and (c) obtaining uniform particles of the pharmacologically-active substance having a mass median diameter of less than 10 microns.