Method and apparatus for the formation of particles

• US 20030047824A1
• Filed: 08/22/2002
• Published: 03/13/2003
• Est. Priority Date: 02/21/1997
• Status: Abandoned Application

• Current Assignee: Nektar Therapeutics UK, Ltd. (Nektar Therapeutics)
• Original Assignee: Bradford Particle Design, PLC (Nektar Therapeutics)
• Inventors: York, Peter, Hanna, Mazen
• Application Number:
  US10/225,943
• Publication Number:
  US 20030047824A1
• Time in Patent Office: Days
• US Class Current: 264/11
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: B01D 11/0403 with a supercritical fluid
• CPC Class Codes: B01D 11/0407 the supercritical fluid acting as solvent for the solute
• CPC Class Codes: B01D 11/0411 the supercritical fluid acting as solvent for the solvent and as anti-solvent for the solute, e.g. formation of particles from solutions
• CPC Class Codes: B01D 11/0488 Flow sheets
• CPC Class Codes: B01J 2/04 in a gaseous medium if combined with suspending the material in a gas, e.g. fluidised beds B01J2/16

Abstract

The invention provides a method and apparatus for forming particles of a substance, comprising (a) introducing into a particle formation chamber, the temperature and pressure in which are controlled, a first supercritical fluid (SCF) and a solution or suspension of the substance in a vehicle, (b) simultaneously introducing an impinging flow of a second supercritical fluid (SCF), at an angle to, and directed at, the direction of flow of the first supercritical fluid, so as to increase the amount of kinetic energy transferred to the solution or suspension; and (c) using either or both of the first and the second supercritical fluids to disperse the solution or suspension, and to extract the vehicle from it, substantially simultaneously and substantially immediately on introduction of the fluids into the particle chamber.

Claims

1. A method for forming particles of a substance, the method comprising (a) introducing into a particle formation chamber, the temperature and pressure in which are controlled, a first supercritical fluid and a solution or suspension of the substance in a vehicle;

(b) simultaneously introducing, into the particle formation chamber, an impinging flow of a second supercritical fluid, at an angle to, and directed at, the direction of flow of the first supercritical fluid; and

(c) using either or both of the first and second supercritical fluids to disperse the solution or suspension, and to extract the vehicle from it, substantially simultaneously and substantially immediately on introduction of the fluids into the particle formation chamber.

2. A method according to claim 1, wherein the first and second supercritical fluid flows are directed at one another in substantially opposite directions.

3. A method according to any one of the preceding claims, wherein the directions of flow of the first supercritical fluid and the solution or suspension are substantially parallel.

4. A method according to claim 3, wherein the directions of flow of the first supercritical fluid and the solution or suspension are coaxial.

5. A method according to claim 1 or claim 2, wherein the solution or suspension is introduced at an angle to the flow of the first supercritical fluid.

6. A method according to any one of the preceding claims, wherein the first and second supercritical fluids are the same.

7. A method according to any one of the preceding claims, wherein the ratio of the solution/suspension flow rate to each supercritical fluid flow rate is between 0.001 and 0.2.

8. A method according any one of the preceding claims, additionally involving collecting the particles, following their formation, in the particle formation chamber.

9. A method according to any one of the preceding claims, which is carried out in a substantially continuous manner.

29. A particulate product formed using the method of any one of claims 1-9 or 26, and/or the apparatus of any one of claims 10-25 or 27.

10. Apparatus for use in a method of forming particles of a substance, comprising a particle formation chamber;

means for controlling the temperature in the chamber at a desired level;

means for controlling the pressure in the chamber at a desired level;

first fluid inlet means for the introduction into the chamber of a first supercritical fluid and a solution or suspension of the substance in a vehicle; and

second fluid inlet means for introducing simultaneously an impinging flow of a second supercritical fluid, at an angle to, and directed at, the direction of flow of the first supercritical fluid, the apparatus being such as to allow dispersion of the solution or suspension, and extraction of the vehicle, to occur substantially simultaneously and substantially immediately on introduction of the fluids into the particle formation chamber, by the action of either or both of the two supercritical fluids.

11. Apparatus according to claim 10, wherein the first fluid inlet means allows the co-introduction of the first supercritical fluid and the solution or suspension in substantially parallel directions.

12. Apparatus according to claim 11, wherein the first fluid inlet means allows the co-introduction of the first supercritical fluid and the solution or suspension coaxially.

13. Apparatus according to any one of claims 10-12, wherein the second fluid inlet means allows the introduction of the second supercritical fluid in a direction substantially opposite to the direction of flow of the first supercritical fluid.

14. Apparatus according to any one of claims 10-13, wherein the first and second fluid inlet means comprise first and second nozzles respectively.

15. Apparatus according to any one of claims 10-14, wherein the first fluid inlet means comprises two nozzles, one for introduction of the first supercritical fluid and one for introduction of the solution or suspension, arranged at an appropriate angle relative to one another.

16. Apparatus according to any one of claims 10-15, wherein the first and second fluid inlet means both form part of a single fluid inlet assembly usable to introduce all fluids into the particle formation chamber.

17. Apparatus according to claim 16, wherein the fluid inlet assembly comprises:

a) a primary nozzle having two or more concentric passages, through which may be introduced a flow of the first supercritical fluid and a flow of the solution or suspension; and

b) a secondary nozzle having at least one passage directed at an angle to the primary nozzle passages, through which secondary nozzle passage a flow of the second supercritical fluid may be introduced,

the outlets of the primary and secondary nozzle passages being positioned so as to allow supercritical fluid flowing through the secondary nozzle to impinge upon supercritical fluid flowing through the primary nozzle.

18. Apparatus according to claim 17, wherein the secondary nozzle passage is coaxial with the primary nozzle passages but points in the opposite direction, so that the outlet end of the secondary nozzle passage faces the outlet ends of the primary nozzle passages.

19. Apparatus according to claim 17 or 18, wherein the primary nozzle passages are of the type which allow pre-filming of at least one of the fluids to occur, immediately prior to its contact with the other fluids.

20. Apparatus according to any one of claims 17-19, wherein the outlet of an inner passage of the primary nozzle occurs either upstream or downstream of that of one or more of the surrounding outer passage(s).

21. Apparatus according to any one of claims 17-20, wherein the secondary nozzle comprises two or more concentric passages.

22. Apparatus according to claim 21, wherein the secondary nozzle passages are of the type which allow pre-filming of at least one of the fluids to occur, immediately prior to its contact with the other fluids.

23. Apparatus according to any one of claims 17-22, wherein the fluid inlet assembly comprises an intermediate chamber located between the primary and the secondary nozzle outlets, in which chamber the fluids may meet and interact.

24. Apparatus according to claim 23, wherein the intermediate chamber is shaped to direct the fluids and/or particles formed from them, away from the point at which the fluids meet.

25. Apparatus according to claim 23 or claim 24, wherein the intermediate chamber is directed roughly perpendicular to the primary and secondary nozzle passages, and in use is downwardly directed so as to allow gravity to contribute to removal of particulate products from the nozzle outlet region.

28. A fluid inlet assembly for use in the apparatus of any one of claims 17-25 or 27.

26. A method for forming particles of a substance, the method being substantially as herein described with reference to the accompanying illustrative drawings.

27. Apparatus for use in a method of forming particles of a substance, the apparatus being substantially as herein described with reference to the accompanying illustrative drawings.