Microparticles

• US 8,409,621 B2
• Filed: 11/13/2007
• Issued: 04/02/2013
• Est. Priority Date: 12/04/2003
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Kim, Kyekyoon, Choi, Hyungsoo, Choy, Young Bin
• Primary Examiner(s): Arnold, Ernst
• Assistant Examiner(s): Yu, Hong
• Application Number:
  US11/939,262
• Publication Number:
  US 20080181964A1
• Time in Patent Office: 1,967 Days
• Field of Search: 424/489, 424/490, 424/491, 424/492, 424/494, 424/495, 424/497, 424/501, 514/772.4, 514/772.5, 514/781, 514/777, 514/779, 264/9
• US Class Current: 424/497
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/1682 Processes

Abstract

A method of forming particles, comprises accelerating a first stream comprising a first liquid, applying a charging voltage of at most 1.5 kV to the first stream, and vibrating the first stream, to form particles.

Claims

1. A method of forming particles, comprising:

accelerating a first stream comprising a first liquid with a carrier stream that imposes frictional force on the first stream to accelerate the first stream;

applying a charging voltage to the first stream;

vibrating the first stream, to form particles; and

separating the particles into sub-particles with a device in-line with a flow of the particles, wherein the device comprises a blade or a nanowire.

2. The method of claim 1, further comprising solidifying the particles.

3. The method of claim 1, wherein the first liquid comprises a hydrophilic polymer.

4. The method of claim 3, wherein the first liquid comprises one or more polymers selected from the group consisting of chitosan, gelatin, alginate, carboxy methyl cellulose, dextran, hydroxypropyl cellulose, poly(acrylamide), poly(acrylic acid), poly(allylamine) hydrochloride, poly(diallyldimethylammonium chloride), poly(N,Ndimethyl acrylamide), poly(ethylene glycol), poly(ethylene oxide), poly(maltotriose), poly(methacrylic acid), poly(N-isopropyl acrylamide), poly(propylene glycol), poly(styrene carboxylic acid), poly(styrene sulphonic acid), poly(styrene sulphonate), poly(vinyl acetate), poly(vinyl alcohol), poly(vinyl butyral), poly(2-vinyl-N-methylpyridinium iodide), poly(4-vinyl-N-methyl pyridinium), poly(2-vinyl pyridine), poly(2-vinyl pyridinium bromide), poly(vinyl pyrrolidone), p(methyl vinyl ether), hydroxyalkyl starch, alkylcellulose, hydroxyalkylcellulose, hydroxyarylcellulose, and copolymers thereof.

5. The method of claim 3, wherein the particles comprise a pharmaceutical composition.

6. The method of claim 3, wherein the particles comprise a core and a shell.

7. The method of claim 6, wherein the particles comprise a plurality of shells.

8. The method of claim 7, wherein the core comprises a pharmaceutical composition.

9. The method of claim 3, wherein the carrier stream is a second stream.

10. The method of claim 9, wherein the second stream surrounds the first stream.

11. The method of claim 1, further comprising forming the first stream by passing the first liquid through a nozzle.

12. The method of claim 11, wherein the nozzle has a diameter greater than ½

of an average diameter of the particles.

13. The method of claim 11, wherein the nozzle has a diameter at least equal to an average diameter of the particles.

14. The method of claim 3, wherein the particles have an average diameter of at least 10 nm to at most 100 um.

15. The method of claim 1, wherein the particles have an average diameter of at least 50 um to at most 100 um, and 90% of the particles have a diameter that is within 2% of an average diameter of the particles.

16. The method of claim 1, wherein the particles have an average diameter of at least 1 um to at most 50 um, and 90% of the particles have a diameter that is within 1 um of an average diameter of the particles.

17. The method of claim 1, further comprising passing the first liquid through a nozzle comprising the device.

21. The method of claim 1, wherein the device is a nanowire.

22. The method of claim 1, wherein the device is a blade.

23. The method of claim 1, wherein the sub-particles are of substantially equal size based on a position of a tip of the device.

24. The method of claim 1, wherein the sub-particles are of different size based on a position of a tip of the device.

18. A method of forming chitosan or alginate particles, comprising:

accelerating a first stream comprising a solution of chitosan or alginate with a second stream that imposes frictional force on the first stream;

applying a charging voltage to the first stream;

vibrating the first stream, to form particles;

separating the particles into sub-particles with a device in-line with a flow of the particles, wherein the device comprises a blade or a nanowire; and

maintaining the sub-particles at a pressure of at least 0.1 mm Hg and of at most 760 mm Hg, while heating the sub-particles to a temperature within ±

50°

C. of the boiling point of water at the pressure;

wherein the accelerating comprises contacting the first stream with the second stream, and the second stream comprises a hydrophobic liquid.

19. The method of claim 18, wherein particles comprising chitosan or alginate have an average diameter of at least 1 um to at most 100 um, wherein 90% of the particles have a diameter that is within 1 um of an average diameter of the particles.

25. The method of claim 18, wherein the device is a nanowire.

26. The method of claim 18, wherein the device is a blade.

27. The method of claim 18, wherein the sub-particles are of substantially equal size based on a position of a tip of the device.

28. The method of claim 18, wherein the sub-particles are of different size based on a position of a tip of the device.

20. A method of forming gelatin particles, comprising:

accelerating a first stream with a second stream,

applying a charging voltage to the first stream;

vibrating the first stream, to form particles;

separating the particles into sub-particles with a device in-line with a flow of the particles, wherein the device comprises a blade or a nanowire, and wherein the accelerating comprises contacting the first stream with the second stream.

29. The method of claim 20, wherein the device is a nanowire.

30. The method of claim 20, wherein the device is a blade.

31. The method of claim 20, wherein the sub-particles are of substantially equal size based on a position of a tip of the device.

32. The method of claim 20, wherein the sub-particles are of different size based on a position of a tip of the device.