Intrapulmonary drug delivery within therapeutically relevant inspiratory flow/volume values

• US 5,509,404 A
• Filed: 07/11/1994
• Issued: 04/23/1996
• Est. Priority Date: 07/11/1994
• Status: Expired due to Term

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Rubsamen, Reid M., Lloyd, Lester J.
• Primary Examiner(s): Lewis, Aaron J.
• Application Number:
  US08/273,375
• Time in Patent Office: 652 Days
• Field of Search: 128/200.14, 128/200.23, 128/204.23
• US Class Current: 128/200.14
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 15/008 Electronic counters
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2016/0039 in the inspiratory circuit
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/8206 battery-operated

Abstract

A method of drug delivery is disclosed wherein a patient'"'"'s inspiratory flow rate and inspiratory volume are simultaneously measured using a portable, hand-held, device which may be electronic and battery-powered or mechanical. Information obtained from the measurement is used to release, into a patient'"'"'s inspiratory flow path, particles of a pharmaceutically active drug. The released particles have a particle size in the range of from about 0.5 to 12 microns. The drug is released when the patient'"'"'s measured inspiratory flow rate is in the range of from about 0.10 to about 2.0 liters/second and the patient'"'"'s inspiratory volume is in the range of from about 0.15 to about 0.8 liters. By measuring inspiratory flow and volume and releasing within the specific parameters with respect to both flow and volume, it is possible to obtain a high degree of repeatability with respect to dosing of a patient and further to deliver a relatively high percentage of the released drug to the patient'"'"'s circulatory system.

Claims

1. A method of drug delivery into a patient'"'"'s airway, comprising:

simultaneously measuring a patient'"'"'s inspiratory flow rate and inspiratory volume;

determining whether the measured inspiratory flow rate and inspiratory volume equals a predetermined inspiratory flow rate and inspiratory volume; and

releasing an aerosolized drug responsive to said measured inspiratory flow rate and inspiratory volume being determined to be equal to said predetermined inspiratory flow rate and inspiratory volume into the patient'"'"'s inspiratory flow at substantially zero velocity at a point of release or at a velocity which reduces to substantially zero after travelling 2 cm or less from a point of release in the absence of the patient'"'"'s inspiration.

2. The method of claim 1 wherein the inspiratory flow rate is in the range of from about 0.2 to about 1.8 liters/second and the inspiratory volume is in the range of from about 0.15 to about 0.40 liters.

3. The method of claim 1, wherein the inspiratory flow rate is in the range of from about 0.15 to about 1.8 liters/second and the inspiratory volume is in the range of from about 0.15 to about 0.25 liters.

4. The method of claim 1 wherein the aerosolized drug has a particle size in the range of from about 0.5 to 12 microns and wherein the drug is released at a velocity of substantially zero relative to the patient'"'"'s inspiratory flow path.

5. The method of claim 1, wherein the measuring and releasing are carried out during a single inhalation of the patient.

6. The method of claim 1 wherein the aerosolized drug is in the form of aerosolized particles of a solution.

7. The method of claim 6, wherein the solution is an aqueous solution.

8. The method of claim 6, wherein the solution is comprised of drug dissolved in a low-boiling point propellant.

9. The method of claim 1, wherein the aerosolized drug is in the form of aerosolized particles of a suspension.

10. The method of claim 9, wherein the suspension is an aqueous suspension.

11. The method of claim 9, wherein the suspension is comprised of drug suspended in a low-boiling point propellant.

12. The method of claim 1, wherein the aerosolized drug is in the form of aerosolized particles of a dry powder.

13. The method of claim 1, wherein the measuring is carried out via electronic air flow measurement components.

14. The method of claim 1, wherein the measuring is carried out via mechanical air flow measurement components.

15. The method of claim 1, wherein the releasing is begun while the inspiratory flow rate is in the range of from about 0.10 to about 2.0 liters/second and the inspiratory volume is in the range of about 0.15 to about 0.80 liters and the releasing is completed outside the range of inspiratory flow rate of about 0.10 to about 2.0 liters/second.

16. The method of claim 1, wherein the releasing is begun while the inspiratory flow rate is in the range of from about 0.10 to about 2.0 liters/second and the inspiratory volume is in the range of about 0.15 to about 0.80 liters and the releasing is completed at an inspiratory volume of above about 0.40 liters.

17. The method of claim 1, wherein the releasing is begun and completed while the inspiratory flow rate is in the range of from about 0.10 to about 2.0 liters/second.

18. The method of claim 17, wherein the releasing is begun and completed while the inspiratory volume is in the range of about 0.15 to about 0.40 liters.

19. The method of claim 1, wherein aerosolized drug is released when the inspiratory flow rate is in a range of from about 0.10 to 2.0 liters/second and the patient'"'"'s inspiratory volume is in a range of from about 0.15 to about 0.80 liters.

20. The method of claim 1, wherein the aerosolized drug is released at a therapeutically relevant inspiratory flow rate value above about 0.10 liters/second and inspiratory volume value above about 0.15 liters.

21. A method of drug delivery, comprising:

simultaneously measuring a patient'"'"'s inspiratory flow rate and inspiratory volume with a portable, hand-held, battery-powered device; and

releasing particles of a pharmaceutically active drug having a particle size in the range of from about 0.5 to 12 microns, the drug being released at a substantially zero rate of velocity relative to the patient'"'"'s inspiratory flow path and occurring when the patient'"'"'s measured inspiratory flow rate is in the range of from about 0.10 to 2.0 liters/second and the patient'"'"'s inspiratory volume is in the range of from about 0.15 to about 0.80 liters.

22. The method of claim 21, wherein the releasing is begun within the inspiratory flow rate of about 0.10 to 2.0 liters/second and the inspiratory volume of about 0.15 to about 0.40 liters.

23. The method of claim 21, wherein the aerosolized drug is a pharmaceutically active respiratory drug.

24. The method of claim 21, wherein the aerosolized drug is a pharmaceutically active systemic drug.

25. The method of claim 21, wherein the aerosolized drug is asteroid selected from the group consisting of beclomethasone dipropionate, flunisolide, fluticasone, budesonide and triamcinolone acetonide.

26. The method of claim 21, wherein the aerosolized drug is a non-steroidal, anti-inflammatory drug.

27. The method of claim 21, wherein the aerosolized drug is selected from the group consisting of isoproterenol, cromolyn sodium, albuterol sulfate, metaproterenol sulfate, salmeterol xinafoate and formotorol.

28. The method of claim 21, wherein the particles have the same size within a range of ±

20%.

29. The method of claim 28, wherein the particles have the same size within a range of ±

10%.

30. The method of claim 29, wherein the particles have the same size within a range of ±

5%.