Device and method for creating aerosols for drug delivery

• US 7,059,319 B2
• Filed: 06/09/2004
• Issued: 06/13/2006
• Est. Priority Date: 05/13/1996
• Status: Expired due to Fees

• Current Assignee: Universidad de Sevilla
• Original Assignee: Universidad de Sevilla
• Inventors: Ganan-Calvo, Alfonso
• Primary Examiner(s): Lewis, Aaron J.
• Application Number:
  US10/865,597
• Publication Number:
  US 20050016526A1
• Time in Patent Office: 734 Days
• Field of Search: 128/200.14, 128/200.21, 128/200.22, 128/203.14, 128/203.25, 128/204.24, 128/204.25
• US Class Current: 128/200.14
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 15/0065 Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• CPC Class Codes: A61M 15/025 Bubble jet droplet ejection devices
• CPC Class Codes: A61M 16/14 by mixing different fluids, one of them being in a liquid phase
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: B01F 23/232 using flow-mixing means for introducing the gases, e.g. baffles
• CPC Class Codes: B01F 25/30 Injector mixers mixing by creating vortex flow B01F25/10
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B05B 1/02 designed to produce a jet, spray, or other discharge of particular shape or nature, e.g. in single drops, or having an outlet of particular shapeB05B1/26, B05B1/28, B05B1/34 take precedence
• CPC Class Codes: B05B 7/0475 with means for deflecting the peripheral gas flow towards the central liquid flow B05B7/0458 takes precedence
• CPC Class Codes: B05B 7/061 with several liquid outlets discharging one or several liquids
• CPC Class Codes: B05B 7/065 an inner gas outlet being surrounded by an annular adjacent liquid outlet
• CPC Class Codes: B05B 7/066 with an inner liquid outlet surrounded by at least one annular gas outlet
• CPC Class Codes: B05B 7/0884 the outlet orifices for jets constituted by a liquid or a mixture containing a liquid being aligned
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: F02M 43/04 Injectors peculiar thereto
• CPC Class Codes: F02M 67/10 : Injectors peculiar thereto, e.g. valve less type
• CPC Class Codes: F02M 69/047 : injectors with air chambers, e.g. communicating with atmosphere for aerating the nozzles F02M69/325 takes precedence
• CPC Class Codes: F02M 69/08 : characterised by the fuel being carried by compressed air into main stream of combustion-air
• CPC Class Codes: F23D 11/106 : medium and fuel meeting at the burner outlet
• CPC Class Codes: G01N 15/1409 : Handling samples, e.g. injecting samples
• CPC Class Codes: G01N 2015/1406 : Control of droplet point
• CPC Class Codes: G01N 21/01 : Arrangements or apparatus for facilitating the optical investigation

Abstract

A drug delivery device and method is disclosed which produces aerosolized particles of pharmaceutically active drug for delivery to a patient by inhalation. The device is comprised of a liquid feeding source such as a channel to which formulation is added at one end and expelled through an exit opening. The feeding channel is surrounded by a pressurized chamber into which gas is fed and out of which gas is expelled from an opening. The opening from which the gas is expelled is positioned directly in front of the flow path of liquid expelled from the feeding channel. Various parameters are adjusted so that pressurized gas surrounds liquid flowing out of the feeding channel in a manner so as to maintain a stable capillary microjet of liquid until the liquid exits the pressure chamber opening and is aerosolized. The aerosolized particles having a uniform diameter in the range of about 1 to 5 microns are inhaled into a patient'"'"'s lungs and thereafter reach the patient'"'"'s circulatory system.

Claims

1. A device, comprising:

a first means for providing a pharmaceutically active drug in liquid form, comprising a cylindrical channel , a liquid entrance port and a liquid exit port;

a second means for providing a second fluid comprising a cylindrical channel positioned concentrically around the first means, the second means comprising a second fluid entrance port and a second fluid exit port;

a pressure chamber for providing a pressurized fluid to an area surrounding the first and second exit ports, the pressure chamber comprising a pressurized fluid entrance port and a pressurized fluid exit port positioned downstream of the first and second exit ports; and

a container having a pharmaceutically active drug therein, the container in fluid connection with the first means for providing a pharmaceutically active drug.

2. The device of claim 1, further comprising:

a third means for providing a third fluid comprising a cylindrical channel positioned concentrically around the second means, the third means comprising a third fluid entrance port and a third fluid exit port.

3. The device of claim 1, wherein the liquid exit port has a diameter in the range of from about 0.002 to about 2 mm, and the pressure chamber exit port has a diameter in the range of about 0.002 mm to about 2 mm.

4. The device of claim 1, wherein the first means cylindrical channel has a diameter in the range of from about 0.01 mm to about 0.4 mm and the pressurized fluid exit port has a diameter in the range of about 0.01 mm to about 0.25 mm.

5. The device of claim 1, wherein the exit port of the first means for providing the drug in liquid form is positioned at a point in the range of about 0.002 mm to about 2 mm from the pressurized fluid exit port.

6. The device of claim 1, wherein the liquid drug has a dynamic viscosity in the range of from about 10⁻

4 to about 1 kg/m/sec.

7. A method of creating an aerosol of a liquid pharmaceutically active drug, comprising:

forcing a pharmaceutically active drug in liquid form through a channel of a feeding source in a manner which causes the liquid to be expelled from an exit opening;

forcing a gas through a pressure chamber in a manner which causes the gas to exit the pressure chamber from an opening positioned in front of a flow path of liquid expelled from the exit opening of the feeding source;

wherein a stable liquid-gas interface is maintained and the liquid forms a stable jet between the feeding source exit opening and the opening of the pressure chamber;

wherein fluctuations in dynamic forces exerted by the gas do not exceed the surface tension forces on surface of the liquid in the pressure chamber; and

allowing the microjet to exit the pressure chamber opening and split into drops by effects of instability.

8. The method of claim 7, wherein the liquid has a viscosity in a range of from about 10⁻

4 to about 1 kg/m/sec.

9. The method of claim 7, wherein the liquid has a viscosity in a range of from about 0.3×

10³¹ 3 to about 5×

10<sup>−

2</sup> kg/m/sec.

10. The method of claim 7, wherein the liquid is forced through the channel at a rate in a range of about 1 nl/sec to about 100 μ

l/sec.

11. The method of claim 7, wherein the liquid is forced through the channel at a rate in a range of about 0.01 to about 10 μ

l/sec.

12. The method of claim 7, wherein the gas is forced through the opening of the pressure chamber at a rate in the range of from about 50/sec to about 2000 m/sec.

13. The method of claim 7, wherein the gas is forced through the opening of the pressure chamber at a rate in the range of from about 100 to 500 m/sec.

14. The method of claim 7, wherein the liquid is expelled from a circular exit opening having a diameter of less than about 0.4 mm and wherein the opening in the pressure chamber is circular and positioned directly in front of the exit opening of the feeding source and has a diameter of less than 0.25 mm and wherein the exit opening of the feeding source is positioned at a point of less than about 0.5 mm from the opening of the pressure chamber.

15. The method of claim 14, wherein the liquid is expelled from a circular exit opening having a diameter in a range of from about 0.1 mm to about 0.4 mm, the pressure chamber exit opening has a diameter in a range of about 0.1 mm to 0.25 mm and the exit opening of the feeding source is positioned at a point in a range of about 0.2 mm to about 0.5 mm from the exit opening of the pressure chamber.

16. A method of administering a drug, comprising:

feeding a pharmaceutically active drug in liquid form through a feeding source to an outlet;

feeding gas through an orifice positioned in front of the feeding source outlet in a direction parallel to a direction of flow out of the feeding source outlet;

wherein the feeding of liquid and feeding of gas are each at a rate relative to each other so as to maintain a stable microjet of liquid which exits the orifice and forms aerosolized particles;

wherein fluctuations in dynamic forces exerted by the gas do not exceed the surface tension forces on surfaces of the liquid;

wherein gas from the pressure chamber surrounds liquid exiting the feeding source outlet which is drawn into the orifice concentrically;

allowing the microjet to exit the pressure chamber orifice and split into drops by effects of instability; and

inhaling the drops into the lungs of a patient.

17. The method of claim 16, wherein gas is forced into an area around the feeding source outlet at a pressure in the range of 100 to 2000 mBar above atmospheric pressure.

18. The method of claim 16, wherein the liquid has a viscosity in the range of from 10⁻

4 to 1 kg/m/sec.

19. The method of claim 16, wherein the aerosolized particles formed are uniform in size to the extent of having a relative size standard deviation of 10 to 30%.