Methods for fine particle formation

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A preferred embodiment of the present invention is shown in FIG.
1 illustrating the flow of fluids and solutions in the method of this invention.
A carbon dioxide reservoir 10 containing liquid carbon dioxide is connected with supercritical carbon dioxide pump 12 via conduit 26.
Supercritical carbon dioxide pump 12 is connected to mixing tee 20 by means of conduit 28, needle valve 72 and conduit 74, through which the carbon dioxide is pumped under conditions at which it becomes a supercritical fluid when it reaches the heated mixing tee 20.
Reservoir for aqueous solution 14 containing a dissolved or suspended substance is connected via conduit 30 to solution pump 16, preferably a high pressure liquid chromatography (HPLC) pump, which is connected via conduit 36, needle valve 32 and conduit 70 to mixing tee 20.
Needle valves 32 and 72 are flow control valves to control the rate of flow of supercritical fluid and aqueous solution to assure that an immiscible mixture is formed in mixing tee 20.
The mixing tee preferably has a low dead volume, e.
g.
less than about 10 .
mu.
l so that an intimate mixture of the supercritical carbon dioxide and the aqueous solution may be formed therein.
Mixing tee 20 is equipped with a heater 18 equipped with heating coils 38 to maintain supercritical temperature therein.
The mixing tee 20 is also equipped with a restrictor capillary 22 to maintain back-pressure in mixing tee 20.
Upon passage of the intimate mixture from the mixing tee 20 through the small diameter capillary restrictor 22, sudden release of the pressure at the exit of the orifice of restrictor capillary 22 occurs and an aerosol comprising gas-borne fine particles of the dissolved substance and aqueous solution 34 is formed.
The particles are collected, further treated, or diluted with air and conducted into drug delivery means or collector 24.
The drug delivery means may be a face mask or mouthpiece for particles to be inhaled, a collector for collecting or solubilizing the particles for injection or other use; or in the experimental model used in the Examples hereof, the apparatus includes a collector for measuring particle sizes by laser diffraction of collected aerosols