Method and apparatus for dispersion of dry powder medicaments

• US 5,785,049 A
• Filed: 09/21/1994
• Issued: 07/28/1998
• Est. Priority Date: 09/21/1994
• Status: Expired due to Term

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Inhale Therapeutic Systems Co.
• Inventors: Lyons, Shirley W., Etter, Jeffery W., Smith, Adrian E., Platz, Robert M., Axford, George S., Burr, John D.
• Primary Examiner(s): Asher, Kimberly L.
• Application Number:
  US08/309,691
• Time in Patent Office: 1,406 Days
• Field of Search: 128/203.15, 128/203.21, 128/203.23, 604/58, 206/528
• US Class Current: 128/203.15
• CPC Class Codes: A61M 15/0036 hollow piercing means
• CPC Class Codes: A61M 15/004 with fixed piercing or cutting means
• CPC Class Codes: A61M 15/0041 with movable piercing or cutting means
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0055 the used dosages being coiled
• CPC Class Codes: A61M 15/0086 Inhalation chambers
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/0233 Conductive materials, e.g. antistatic coatings for spark prevention
• CPC Class Codes: A61M 2205/073 Syringe, piston type
• CPC Class Codes: A61M 2205/6045 having complementary physical shapes for indexing or registration purposes

Abstract

A method for aerosolizing a powdered medicament comprises coupling a powder inlet end of a feed tube with a penetration in a receptacle containing the powder. Powder is drawn upward through the tube and dispersed in a high pressure gas stream flowing past a portion of the feed tube. Apparatus comprise the feed tube mounted within a base enclosure proximate a holder for one or more receptacles, which may be in the form of a cartridge containing a plurality of receptacles formed in a continuous web. The cartridge may be reciprocated relative to the feed tube and a separate piercing mechanism in order to sequentially piercing the receptacle and thereafter couple the feed tube through the resulting penetration for extracting the powder. Alternatively, penetration(s) through the receptacle may be formed as the feed tube is coupled, or some penetrations formed prior to coupling with other penetrations formed at the time of coupling.

Claims

1. A method for aerosolizing a powder contained in a receptacle having an access surface, said method comprising

coupling a powder inlet end of a feed tube having a central axis with a penetration in the access surface;

and

flowing a high pressure gas stream past a portion of the feed tube that is spaced apart from the inlet and the gas stream converging with the portion at an acute angle as measured between the gas stream and the central axis at the inlet end, so that a predetermined amount of powder in the receptacle is fluidized, drawn axially through the tube, and dispersed in the high velocity gas stream to form an aerosol.

2. A method as in claim 1, further comprising forming the penetration in the access surface prior to inserting the feed tube.

3. A method as in claim 1, wherein the penetration in the access surface is formed as the powder inlet end is inserted.

4. A method as in claim 1, further comprising forming at least two spaced-apart penetrations in the access surface, wherein the other penetration permits fluidization air to sweep the receptacle as the powder is drawn through the feed tube.

5. A method as in claim 1, further comprising advancing a plurality of powder-containing receptacles past the feed tube, whereby powder may be drawn sequentially and dispersed from each receptacle.

6. A method as in claim 1, wherein a fixed volume of high pressure gas in the range from 2 ml to 25 ml (STP) is flowed past the outlet end, resulting in a discrete volume of aerosolized powder, further comprising capturing substantially the entire volume of aerosolized powder in a plume capture chamber, wherein the powder is available for subsequent inhalation by a patient.

7. A method as in claim 6, wherein at least a portion of gas in the chamber is directed back to the receptacle to provide fluidization gas as the powder is withdrawn through the feed tube.

8. A method as in claim 1, wherein the high pressure air stream is flowed past the feed tube at an angle in the range from 12.5°

to 65°

relative to the axial direction.

9. A method as in claim 1, wherein the predetermined amount is at least 70% by weight of the amount of powdered medicament initially present in the receptacle.

10. Apparatus for aerosolizing a powder contained in a receptacle having a puncturable access surface, said apparatus comprising:

a base enclosure;

a holder within the base enclosure for supporting the receptacle at a fluidization location;

a feed tube within the base enclosure having an inlet end at a fluidization location; and

means for flowing a high pressure gas stream past a portion of the feed tube which is spaced apart from the inlet end, wherein the gas stream converges with the feed tube at an acute angle as measured between the gas stream and the inlet end, wherein powder is fluidized from a receptacle in the holder and extracted axially through the tube and dispersed in the high pressure air stream to form an aerosol.

11. Apparatus as in claim 10, wherein the receptacle holder comprises means for advancing a continuous web which carries a plurality of receptacles thereon, whereby individual receptacles can be sequentially moved to the fluidization location.

12. Apparatus as in claim 11, wherein the means for advancing comprises a cartridge which is removably mounted in the base enclosure, said continuous web being movably mounted in said cartridge.

13. Apparatus as in claim 12, wherein the feed tube is fixedly mounted within the base enclosure and wherein the means for advancing comprises means for reciprocating the cartridge relative to the feed tube.

14. Apparatus as in claim 13, further comprising means for piercing a hole in the access surface prior to inserting the inlet end of the feed tube.

15. Apparatus as in claim 14, wherein the piercing means forms at least two spaced-apart holes in the access surface, wherein one hole couples to the feed tube and the other permits the entry of fluidization air to sweep the receptacle as powder is extracted through the feed tube.

16. Apparatus as in claim 15, further comprising a plume capture chamber in the base enclosure and means for directing air from an interior of the plume capture chamber to the receptacle, whereby said directed air will enter the receptacle to provide fluidization air as powder is drawn therefrom.

17. Apparatus as in claim 13, further comprising means for piercing a hole in the access surface simultaneously with inserting the inlet end of the feed tube.

18. Apparatus as in claim 15, wherein the piercing means comprises a fixed piercing mechanism which is disposed to piercing mechanism holes in the access surface of a receptacle as the cartridge is reciprocated relative to the feed tube.

19. Apparatus as in claim 10, further comprising a plume capture chamber disposed on the base to capture powder dispersed in said high velocity air stream, said chamber having a mouth piece at an end remote from the base.

20. Apparatus as in claim 10, wherein the means for flowing comprises a pump or other pressurized gas source in the base enclosure for abruptly releasing a pressurized volume of air to form the high velocity air stream.

21. Apparatus for aerosolizing a powder, said apparatus comprising:

a feed tube having an inlet end, an outlet end, and a lumen defining an axial flow path therebetween;

means for flowing at least one high pressure gas stream past said outlet end in a direction which converges with the axial flow path at an angle in the range from 12.5°

to 65° and

a diffuser tube extending from the outlet end of the feed tube and having a lumen coaxially aligned with the feed tube lumen, wherein the diameter of the diffuser tube lumen increases in a direction away from the outlet end of the feed tube.

22. Apparatus as in claim 21, wherein the flowing means includes at least one gas conduit which converge with the flow path.

23. Apparatus as in claim 21, wherein the flowing means provides a total lumen area (A₁) in the range from 0.05 mm² to 0.3 mm² and the feed tube has a lumen area (A₂) in the range from 0.5 mm² to 10 mm².

24. Apparatus as in claim 21, wherein the diffuser tube lumen diverges at a half angle of 2°

to 10°

over a length in the range from 0.5 cm to 5 cm.

25. Apparatus as in claim 21, further comprising a mixing volume disposed between the outlet end of the feed tube and the diffuser tube, said mixing volume having a constant diameter along its length.

26. Apparatus as in claim 25, wherein the mixing volume has a length which is from one to five times its diameter.

27. An improved method for aerosolizing a powdered medicament, said method being of the type wherein the powder is entrained and suspended in a flowing gas stream, wherein the improvement comprises inserting an inlet end of the feed tube into a receptacle containing the powdered medicament and flowing a high pressure gas stream past an outlet end of the feed tube which is downstream from the inlet end to induce air flow from the receptacle, through the tube, and into the flowing gas stream, wherein the powdered medicament is entrained in the air flow through the tube and combined with the high pressure gas stream, wherein the powdered medicament passes through a diffuser tube which diverges in a direction away from the outlet end of the feed tube and wherein the gas stream is flowed past the outlet end at an acute angle as measured between the gas stream and the inlet end.

28. A method for aerosolizing a powder contained in a receptacle having an access surface, said method comprising:

coupling a powder inlet end of a feed tube having a central axis with a penetration in the access surface; and

flowing a high pressure gas stream past a portion of the feed tube that is spaced apart from the powder inlet, the gas stream converging with the portion at an acute angle as measured between the gas stream and the central axis at the inlet end, the angle being selected to provide a sufficient gas flow through the feed tube so that a predetermined amount of powder in the receptacle is fluidized, drawn axially through the tube, and dispersed in the high velocity gas stream to form an aerosol, the angle further being selected to create shear forces within the feed tube sufficient to beak down agglomerates within the powder.

29. A method as in claim 28, further comprising forming the penetration in the access surface prior to inserting the feed tube.

30. A method as in claim 28, wherein the penetration in the access surface is formed as the powder inlet end is inserted.

31. A method as in claim 28, further comprising forming at least two spaced-apart penetrations in the access surface, wherein the other penetration permits fluidization air to sweep the receptacle as the powder is drawn through the feed tube.

32. A method as in claim 28, further comprising advancing a plurality of powder-containing receptacles past the feed tube, whereby powder may be drawn sequentially and dispersed from each receptacle.

33. A method as in claim 28, wherein a fixed volume of high pressure gas in the range from 2 ml to 25 ml (STP) is flowed past the outlet end, resulting in a discrete volume of aerosolized powder, further comprising capturing substantially the entire volume of aerosolized powder in a plume capture chamber, wherein the powder is available for subsequent inhalation by a patient.

34. A method as in claim 33, wherein at least a portion of gas in the chamber is directed back to the receptacle to provide fluidization gas as the powder is withdrawn through the feed tube.

35. A method as in claim 28, wherein the high pressure air stream is flowed past the feed tube at an angle in the range from 12.5°

to 65°

relative to the axial direction.

36. A method as in claim 28, wherein the predetermined amount is at least 70% by weight of the amount of powdered medicament initially present in the receptacle.

37. A method for aerosolizing a powder contained in a receptacle, said method comprising;

coupling a powder inlet end of a feed tube with a penetration in the receptacle; and

abruptly releasing a gas from a pressurized source and directing the released gas in a high pressure gas stream past a portion of the feed tube which is spaced apart from the powder inlet, wherein the high velocity air stream is flowed cast the outlet end of the feed tube at an angle in the range from 12.5°

to 65°

as measured between the gas stream and the inlet end;

wherein the high pressure gas stream fluidizes powder in the receptacle and draws the fluidized powder through the reed tube and into the high pressure gas stream to form the aerosol, and wherein the high pressure gas stream produces a flow at the portion of the feed tube sufficient to provide shear forces to break down agglomerates within the powder.

38. A method as in claim 37, further comprising forming the penetration in the access surface prior to inserting the feed tube.

39. A method as in claim 37, wherein the penetration is the access surface is formed as the powder inlet end is inserted.

40. A method as in claim 37, further comprising forming at least two spaced-apart penetrations in the access surface, wherein the inlet end is coupled with one penetration and the other penetration permits fluidization air to sweep the receptacle as the powder is drawn through the feed tube.

41. A method as in claim 37, further comprising advancing a plurality of powder-containing receptacles past the feed tube, whereby powder may be drawn sequentially and dispersed from each receptacle.

42. A method as in claim 37, further comprising capturing substantially the entire volume of aerosolized powder in a plume capture chamber, wherein the powder is available for subsequent inhalation by a patient.

43. A method as in claim 42, wherein at least a portion of gas in the chamber is directed back to the receptacle to provide fluidization gas as the powder is withdrawn through the feed tube.

44. A method as in claim 37, wherein at least 70% by weight of the powder initially present in the receptacle is fluidized and drawn into the high pressure gas stream.

45. Apparatus for aerosolizing a powder, said apparatus comprising:

a feed tube having an inlet end, an outlet end, and a lumen defining an axial flow path therebetween; and

at least one gas conduit spaced apart from the inlet end of the feed tube for flowing at least one high pressure gas stream past said outlet end in a direction which converges with the axial flow path at an acute angle relative to the inlet end; and

a diffuser tube extending from the outlet end of the feed tube and having a lumen coaxially aligned with the feed tube lumen, wherein the cross sectional area of the diffuser tube lumen increases in a direction away from the outlet end of the feed tube.

46. Apparatus as in claim 45, wherein the acute angle is in the range from about 12.5°

to 65°

.

47. Apparatus as in claim 45, wherein the gas conduit provides a total lumen area (A₁) in the range from 0.05 mm² to 0.3 mm² and the feed tube has a lumen area (A₂) in the range from 0.5 mm² to 10 mm².

48. Apparatus as in claim 45, wherein the diffuser tube lumen diverges at a half angle of 2°

to 10°

over a length in the range from 0.5 cm to 5 cm.

49. Apparatus as in claim 45, further comprising a mixing volume disposed between the outlet end of the feed tube and the diffuser tube, said mixing volume having a constant diameter along its length.

50. Apparatus as in claim 49, wherein the mixing volume has a length which is from one to five times its diameter.