Ultrasonic method and apparatus for producing particles having a controlled size distribution

Patent metadata

Field	Value
Publication number	US-9855538-B2
Application number	US-201414772255-A
Country	US
Kind code	B2
Filing date	Mar 4, 2014
Priority date	Mar 8, 2013
Publication date	Jan 2, 2018
Grant date	Jan 2, 2018

Abstract

An ultrasonic apparatus for producing particles of a pharmaceutical agent or other material comprises a flow-through ultrasonic horn comprising an inlet, an outlet, and an interior channel that connects the inlet to the outlet for flow of a fluid therethrough. The ultrasonic horn is connectable to a transducer, and a crystallization tube is adjacent to the ultrasonic horn. The crystallization tube comprises an inlet port and outlet port for flow of an antisolvent therethrough, and it further includes a side access port. The outlet of the ultrasonic horn is inserted into the side access port so as to be in fluid communication with the crystallization tube.

First claim

The invention claimed is:

1. A ultrasonic method of forming particles having a controlled size distribution, the ultrasonic method comprising:
driving an ultrasonic horn at a resonance frequency thereof, the ultrasonic horn comprising an inlet, an outlet and an interior channel connecting the inlet to the outlet for passage of a fluid therethrough;
delivering a solution comprising a solute and a solvent into the inlet while the outlet is immersed in a continuous flow of antisolvent, the solution flowing through the interior channel and into the antisolvent;
ultrasonically dispersing the solution in the antisolvent, thereby forming nucleation sites comprising the solute; and
forming particles comprising the solute at the nucleation sites.

2. The ultrasonic method of claim 1 , wherein the solute comprises a first solubility in the solvent and a second solubility in the antisolvent, a ratio of the first solubility to the second solubility being at least about 10:1.

3. The ultrasonic method of claim 2 , wherein the ratio of the first solubility to the second solubility is at least about 100:1.

4. The ultrasonic method of claim 1 , wherein the solute comprises a pharmaceutical agent, the solution being a drug solution.

5. The ultrasonic method of claim 1 , wherein the solution is delivered into the inlet at a flow rate of from about 2 mL/min to about 6 mL/min.

6. The ultrasonic method of claim 1 , wherein the continuous flow of antisolvent has a flow rate of from about 25 mL/min to about 85 mL/min.

7. The ultrasonic method of claim 1 , wherein the solution and the antisolvent do not contain a surfactant.

8. The ultrasonic method of claim 1 , wherein the solvent is substantially miscible in the antisolvent.

9. The ultrasonic method of claim 1 , wherein the solvent comprises an organic solvent.

10. The ultrasonic method of claim 1 , wherein the antisolvent comprises an aqueous solvent.

11. The ultrasonic method of claim 1 , wherein the particles form in a mixing region of the antisolvent adjacent to the outlet of the ultrasonic horn.

12. The ultrasonic method of claim 11 , wherein a concentration of the solvent in the mixing region is substantially constant.

13. The ultrasonic method of claim 11 , wherein the mixing region is at a substantially constant temperature.

14. The ultrasonic method of claim 1 , further comprising removing the particles from the antisolvent downstream of the outlet.

15. The ultrasonic method of claim 1 , wherein the particles have an average particle size in the range of from about 0.1 micron to about 10 microns.

16. An ultrasonic apparatus for producing particles having a controlled size distribution, the ultrasonic apparatus comprising:
a flow-through ultrasonic horn comprising an inlet, an outlet, and an interior channel connecting the inlet to the outlet for flow of a fluid therethrough, the ultrasonic horn being connectable to a transducer; and
a crystallization tube adjacent to the ultrasonic horn, the crystallization tube comprising an inlet port and outlet port for flow of an antisolvent therethrough and further comprising a side access port, wherein the outlet of the ultrasonic horn is inserted into the side access port so as to be in fluid communication with the crystallization tube.

17. The ultrasonic apparatus of claim 16 , wherein the side access port defines an angle θ with respect to the inlet port of the crystallization tube, the angle θ being from about 30° to about 150°.

18. The ultrasonic apparatus of claim 16 , further comprising a pump connected to the inlet port of the crystallization tube for driving the antisolvent therethrough, and further comprising a pump connected to the inlet of the ultrasonic horn for driving the solution therethrough.

19. The ultrasonic apparatus of claim 16 , wherein the ultrasonic horn comprises more than one inlet.

20. The ultrasonic apparatus of claim 16 , wherein the ultrasonic horn comprises more than one outlet.

Assignees

• Univ Illinois

Inventors

• Suslick Kenneth S
• Zeiger Bradley W
• Kim Hyo Na

Classifications

• B01J2/18 Primary

  using a vibrating apparatus · CPC title

• B05B7/0012

  Apparatus for achieving spraying before discharge from the apparatus · CPC title

• A61J3/02

  into the form of powders (pulverising in general B02C) · CPC title

• B05B17/063 Primary

  having an internal channel for supplying the liquid or other fluent material · CPC title

• B05B17/0676

  Feeding means · CPC title