U.S. patent application number 10/478172 was filed with the patent office on 2004-12-16 for device.
Invention is credited to Braithwaite, Philip.
Application Number | 20040251318 10/478172 |
Document ID | / |
Family ID | 9915382 |
Filed Date | 2004-12-16 |
United States Patent
Application |
20040251318 |
Kind Code |
A1 |
Braithwaite, Philip |
December 16, 2004 |
Device
Abstract
There is described an air amplifying system comprising an
amplifying fluid jet provided with a fluid inlet and a fluid
outlet, the fluid outlet being linked to an outlet nozzle via an
amplifying passage, the amplifying passage also being linked to a
powder chamber, said chamber being adapted for non-laminar powder
flow, such that fluid travelling from the fluid outlet of the jet
draws extraneous air and aerosolised powder through the powder
chamber so that the extraneous air and aerosolised powder mix with
the amplifying fluid in the amplifying passage and the amplified
mixture exits through the outlet nozzle. There is also described a
powder delivery device comprising such an air amplifying system and
a method of treatment related thereto.
Inventors: |
Braithwaite, Philip;
(Tewkesbury, GB) |
Correspondence
Address: |
BROMBERG & SUNSTEIN LLP
125 SUMMER STREET
BOSTON
MA
02110-1618
US
|
Family ID: |
9915382 |
Appl. No.: |
10/478172 |
Filed: |
July 2, 2004 |
PCT Filed: |
May 27, 2002 |
PCT NO: |
PCT/GB02/02251 |
Current U.S.
Class: |
239/419.5 |
Current CPC
Class: |
A61M 11/06 20130101;
A61M 15/0008 20140204; A61M 2202/064 20130101; A61M 11/002
20140204; A61M 15/0086 20130101; A61M 2206/16 20130101 |
Class at
Publication: |
239/419.5 |
International
Class: |
F23D 011/16 |
Foreign Application Data
Date |
Code |
Application Number |
May 26, 2001 |
GB |
0112888.3 |
Claims
1. An air amplifying system comprising an amplifying fluid jet
provided with a fluid inlet and a fluid outlet, the fluid outlet
being linked to an outlet nozzle via an amplifying passage, the
amplifying passage also being linked to a powder chamber, said
chamber being adapted for non-laminar powder flow, such that fluid
travelling from the fluid outlet of the jet draws extraneous air
and aerosolised powder through the powder chamber so that the
extraneous air and aerosolised powder mix with the amplifying fluid
in the amplifying passage and the amplified mixture exits through
the outlet nozzle characterised in that the powder chamber is an
annular chamber which is adapted to provide non-laminar flow of the
powder.
2. An air amplifying system according to claim 1 characterised in
that the vacuum created by the exit of the gas stream from the
amplifying jet creates a vacuum in the powder chamber and an
entrainment air flow through a powder.
3. An air amplifying system according to claim 2 characterised in
that the entrainment air flow is sufficient to cause
deagglomeration and/or entrainment and then subsequent
aerosolisation of the powder.
4. (Cancelled)
5. An air amplifying system according to claim 1 characterised in
that system comprises an annular powder chamber and an axial fluid
jet.
6. An air amplifying system according to claim 5 characterised in
that the powder chamber is substantially circumferential to the
body of the amplifying system and the fluid jet is axial to the
body.
7. An air amplifying system according to claim 1 characterized in
that the annular powder chamber comprises a male and a female
portion.
8. An air amplifying system according to claim 7 characterised in
that the outlet end of the fluid jet comprises a frusto conical
male member which fits into a female portion of the powder
chamber.
9. An air amplifying system according to claim 7 characterised in
that the separation between the male and female members (the
clearance) is from 500 to 2000 .mu.m.
10. An air amplifying system according to claim 9 characterised in
that the clearance is about 1000 .mu.m.
11. An air amplifying system according to claim 10 characterised in
that the diameter of the jet is from 100 to 500 .mu.m.
12. An air amplifying system according to claim 11 characterised in
that diameter of the jet is from 200 to 300 .mu.m.
13. An air amplifying system according to claim 12 characterised in
that diameter of the jet is about 250 .mu.m.
14. An air amplifying system according to claim 1 characterised in
that the diameter of the nozzle is from 100 .mu.m to 1500
.mu.m.
15. An air amplifying system according to claim 14 characterised in
that the diameter of the nozzle is from 400 m to 1200 .mu.m.
16. An air amplifying system according to claim 15 characterised in
that the diameter of the nozzle is from 400 .mu.m to 600 .mu.m.
17. An air amplifying system according to claim 16 characterised in
that the diameter of the nozzle is about 500 .mu.m.
18. An air amplifying system according to claim 1 characterised in
that the diameter of the nozzle is greater than the diameter of the
jet.
19. An air amplifying system according to claim 18 characterised in
that the ratio of the diameter of the jet to the diameter of the
nozzle is from 1:8 to 1:2.
20. An air amplifying system according to claim 19 characterised in
that the ratio of the diameter of the jet to the diameter of the
nozzle is from 1:4 to 1:2.
21. An air amplifying system according to claim 20 characterised in
that the ratio of the diameter of the jet to the diameter of the
nozzle is 1:2.
22. An air amplifying system according to claim 1 characterised in
that the chamber is provided with a powder reservoir or a powder
metering member adjacent an inlet to the powder chamber.
23. An air amplifying system according to claim 22 characterised in
that the powder reservoir and/or metering member is contiguous with
the powder chamber.
24. An air amplifying system according to claim 22 characterised in
that the powder chamber is connected to the powder reservoir and/or
metering member by one or more conduits.
25. An air amplifying system according to claim 1 characterised in
that the system comprises a plurality of nozzles.
26. An air amplifying system according to claim 1 characterised in
that the and/or a plurality fluid jets.
27. An air amplifying system according to claim 26 characterised in
that the plurality of jets comprises a plurality of interlocking
jets.
28. An air amplifying system according to claim 27 characterised in
that each jet is provided with a powder inlet.
29. A powder delivery device which comprises a delivery passage, a
powder reservoir and/or a metering member adapted to present a
measured dose of powder to the delivery passage characterised in
that the powder delivery device is provided with an air amplifying
system according to claim 1.
30. A powder delivery device according to claim 29 characterised in
that the air amplifying system creates an entrained air flow
through the powder reservoir and/or metering member.
31. A powder delivery device according to claim 30 characterised in
that the entrained air flows through the powder which is presented
either direct from the reservoir or from the metering member.
32. A powder delivery device according to claim 31 characterised in
that the entrained air inlet is positioned adjacent to a first side
of the reservoir and/or metering member and a vacuum is created
adjacent a second, opposite side of the reservoir and/or metering
member.
33. A powder delivery device according to claim 30 characterised in
that a further inlet tube is provided which is adapted to introduce
entrainment air into the reservoir/metering member.
34. A powder delivery device according to claim 30 characterised in
that the entrained air flow is sufficient to both deagglomerate and
aerosolise the powder.
35. A powder delivery device according to claim 29 characterised in
that the device is an inhalation device.
36. A powder delivery device according to claim 35 characterised in
that the inhalation device is a dry powder inhaler.
37. A powder delivery device according to claim 35 characterised in
that the amplifying system is arranged to provide the separate,
sequential or simultaneous operation of the jet(s) to enable the
creation of an aerosolised powder which coincides with the
inspiration of a patient.
38. A powder delivery device according to claim 29 characterised in
that the fluid used in the fluid jet is a gas.
39. A powder delivery device according to claim 38 characterised in
that the gas is generated from the volatilisation of a volatile
propellant.
40. A powder delivery device according to claim 29 characterised in
that the fluid flow is generated by an electric motor.
41. A powder delivery device according to claim 29 characterised in
that the fluid flow is generated by a manually primed piston.
42. A powder delivery device according to claim 39 characterised in
that the propellant is a non-CFC propellant.
43. A powder delivery device according to claim 42 characterised in
that the propellant is a hydrofluoroalkane (HFA).
44. A powder delivery device according to claim 43 characterised in
that the HFA propellant is selected from those disclosed in
EP0372777, WO91/04011, WO91/11173, WO91/11495 and WO91/14422.
45. A powder delivery device according to claim 43 characterised in
that the propellant is a fluoroalkane.
46. A powder delivery device according to claim 45 characterised in
that the fluoroalkane is a fluoromethane, a fluoroethane or a
mixture of fluoroalkanes.
47. A powder delivery device according to claim 46 characterised in
that the fluoroalkane is selected from the group
trichlorofluoromethane, dichlorodifluoromethane,
1,2-dichlorotetrafluorethane, trichlorotrifluoroethane and
chloropentafluoroethane.
48. A powder delivery device according to claim 47 characterised in
that the fluoroalkane is HFA 134 (1,1,1,2-tetrafluoroethane).
49. A powder delivery device according to claim 48 characterised in
that the fluoroalkane is HFA 227.
50. A powder delivery device according to claim 36 characterised in
that the inhaler is one described in European Patent application
No. 0 539 469.
51. A powder delivery device according to claim 29 characterised in
that the metering member comprises a powder housed in a spool and
spool carrier.
52. A powder delivery device according to claim 29 characterised in
that the metering member is a capsule.
53. A powder delivery device according to claims 51 or 52
characterised in that the device is provided with means for opening
the metering member.
54. A powder delivery device according to claim 51 characterised in
that the spool carrier is an integral part of the delivery
device.
55. A powder delivery device according to claim 29 characterised in
that the powder is selected from the group of drugs for the
treatment of asthma, COPD or respiratory infections such as
.beta..sub.2-agonists; fenoterol, formoterol, pirbuterol,
reproterol, rimiterol, salbutarnol, salmeterol and terbutaline;
non-selective beta-stimulants such as isoprenaline; xanthine
bronchodilators; theophylline, aminophylline and choline
theophyllinate; anticholinergics such as ipratropium bromide; mast
cell stabilisers, such as sodium crornoglycate and ketotifen;
bronchial anti-inflammatory agents, such as nedocromil sodium;
steroids, such as beclomethasone dipropionate, fluticasone,
budesonide and flunisolide; and combinations thereof.
56. A powder delivery device according to claim 55 characterised in
that the combination of powders is selected from steroids, such as
beclomethasone dipropionate, fluticasone, budesonide and
flunisolide; and combinations of to .beta..sub.2-agonists, such as,
formoterol and salmeterol.
57. A powder delivery device according to claim 29 characterised in
that the powder is systemically active.
58. A powder delivery device according to claim 57 characterised in
that the powder is selected from a proteinaceous compounds and/or
macromolecules, such as hormones and mediators, such as insulin,
human growth hormone, leuprolide and alpha interferon; growth
factors, anticoagulants, immunomodulators, cytokines and nucleic
acids.
59. A powder delivery device according to claim 29 characterised in
that the powder is a combination selected from a powder as defined
by claim 55 and a powder as defined by claim 56.
60. A powder delivery device characterised in that the delivery
device provides a high FPF and low powder retention.
61. A powder delivery device according to claim 60 characterised in
that the device is a dry powder inhaler.
62. A powder delivery device according to claim 60 characterised in
that the air amplifier comprises a substantially axial jet and a
substantially annular deagglomeration chamber.
63. A powder delivery device according to claims 60 or 61
characterised in that the device delivers an FPF of at least 70%
w/w.
64. A powder delivery device according to claim 63 characterised in
that the device delivers an FPF of at least 80% w/w.
65. A powder delivery device according to claim 664 characterised
in that the device delivers an FPF of at least 90% w/w.
66. A powder delivery device according to claim 60 or 61
characterised in that the device provides a powder retention of
less than 10% w/w.
67. A powder delivery device according to claim 66 characterised in
that the device provides a powder retention of less than 5%
w/w.
68. A powder delivery device according to claim 67 characterised in
that the device provides a powder retention of less than 2%
w/w.
69. A method of administering a medicament which comprises the use
of a powder delivery device according to claim 29.
70. A method of treatment of a patient with a respiratory disorder
which comprises the administration of a medicament using a powder
delivery device according to claim 35.
71. A method of treatment of a patient with a systemic disorder
which comprises the administration of a medicament using a powder
delivery device according to claim 29.
72. A method of delivering a powder wherein the powder has a high
FPF and a low powder retention which comprises the use of a
delivery device comprising an air amplifier.
73. A method of delivering a powder according to claim 72
characterised in that the air amplifier comprises a substantially
axial jet and a substantially annular deagglomeration chamber.
74. A method of treatment of a patient suffering from a respiratory
disorder which comprises the delivery of a medicament powder
wherein the powder has a high FPF and low powder retention.
75. An air amplifying system or a powder delivery device
substantially as described with reference to the accompanying
drawings.
Description
[0001] This invention relates to a novel air amplifying system and
a novel powder delivery device comprising such a system, for
example, a medicament delivery device, such as an inhaler.
[0002] In particular the invention provides a novel form of dry
powder inhaler and a method of delivering a powder using such an
inhaler.
[0003] Conventional powder delivery devices, such as dry powder
inhalers (DPIs), deliver a powder dosage by the aerosolisation of
the powder, the aerosolisation being largely driven by the
inhalation of the patient. One disadvantage with these conventional
DPIs is that the extent of aerosolisation, and therefore the
consistency of the dosage delivered, is dependent upon, inter alia,
the inspiratory flow of the patient, the nature of the air passage
and the nature of the formulation.
[0004] Attempts have been made to improve on conventional DPIs by
using, for example, an air jet directed at or across a powder.
However, such systems suffer from a number of disadvantages in
that, inter alia,
[0005] (i) A powder container may be difficult to completely empty,
giving rise to problems with dosage consistency and with efficiency
of delivery. There may also be a lack of any real element of
control of the air stream.
[0006] (ii) There is no amplification, i.e., the volume of air
entering the device is the same as the volume of air leaving the
device; which nay limit the efficiency of powder
aerosolisation.
[0007] (iii) Air flowing across the powder due to the inhalation of
a patient can only lift the powder into the airstream and therefore
does not efficiently aerosolise the powder.
[0008] Conventional metered dose inhalers (MDIs) attempt to address
this problem by the use of a volatile propellant to create a
pressure sufficient to aerosolise the medicament. However, one
disadvantage of MDIs is that the combination of a volatile
propellant to create a pressure sufficient to aerosolise the
medicament, and a solubilised medicament can give rise to blocking
or clogging of the valve through which the aerosolised medicament
is emitted. In addition MDIs are disadvantageous in that, inter
alia, they lack the ability to co-ordinate actuation with
inhalation, and suffer from high drug impaction in the oropharynx,
although breath actuation systems may overcome these issues to a
certain extent.
[0009] U.S. Pat. No. 6,158,675 to Nathaniel Hughes, describes a
microatomising device which uses a vortex accumulation resonant
chamber the use of which creates a vacuum to enable outside
entrainment air to be drawn into the device, lowering the speed of
delivery of the medicament particles to the lung.
[0010] U.S. Pat. No. 4,114,615 to Draco AB, describes an aerosol
inhalation device which, inter alia, activates a liquid propellant.
In use, the propellant flows past a capillary arranged in a
medicament container. The specification describes, at column 3,
lines 59 to 63, that when the propellant passes across the top of
the capillary, the medicament is drawn from the chamber.
[0011] U.S. Pat. No. 5,657,794 to Inhale Therapeutics Inc.
describes a dry powder inhaler which is provided with a curved
section of a passage which creates a Venturi effect to empty a
powder containing receptacle. A feed tube is positioned so that an
inlet end of the tube enters the receptacle and a high velocity gas
stream is released which creates a `low pressure region` at the
outlet end of the feed tube. This low pressure region that is
created acts to draw fluidisation air into the receptacle, to
fluidise and/or aerosolise the powder and extract the powder
through the feed tube and into the high velocity gas stream.
Although the device addresses the problem of more complete emptying
of the powder receptacle by the utilisation of a walled passage
which communicates and co-operates with a depression in the powder
receptacle to create a Venturi effect, such a device may, inter
alia, have limitations in efficiency of powder aerosolisation and
may not address all previously mentioned problems of prior art
devices.
[0012] In addition, one particular disadvantage of the Inhale
device is its large size. The Inhale system generates a
substantially laminar flow of, e.g. powder. Thus, in order to
achieve the necessary deagglomeration, a large dose of high impact
air must be delivered in order to achieve the magnitude of impact
required for deagglomeration of the powder. Thus, the Inhale system
suffers from the disadvantage that, inter alia, is cumbersome and
does not readily lend itself to a portable delivery system.
[0013] International Patent application No. WO 01/87378 to Dura,
describes a dry powder inhaler wherein a powder port extends into a
dispersion tube. A small burst of compressed gas is released into
the dispersion tube and expands, the rapidly moving and expanding
gas disperses the powder and entrains the powder in the gas flow.
However, the device suffers from the disadvantage that, inter alia,
deagglomeration of the powder remains unsatisfactory.
[0014] U.S. Pat. No. 5,740,794--Inhale describes an inhalation
apparatus which comprises, inter alia, a powder containing
receptacle. A feed tube is positioned so that an inlet end of the
tube enters the receptacle and a high pressure gas stream is
released which creates a `low pressure region` at the outlet end of
the feed tube. Tis low pressure region acts to draw fluidisation
air into the receptacle, to fluidise and extract the powder through
the feed tube and into the high velocity gas stream.
[0015] However, there is no disclosure that the powder will undergo
a circulatory trajectory on its way to the mouthpiece. Indeed, the
disclosure, for example in FIG. 12 of Inhale describes a system
wherein the powder is evacuated from the receptacle through a
`central` feed tube, no substantial circulatory motion being
introduced.
[0016] Furthermore, the description refers to an "undisrupted" flow
path for the powder, which would lead one to conclude that a "feed
tube" which is central rather, than one which is peripheral, is
desirable.
[0017] International Patent Application No. WO 00/45878--Fraunhofer
describes a device which utilises a vacuum aerosolisation of a
liquid/powder. However, it is notable, particularly from FIG. 2,
that the powder/liposome travels through the central conduit with
compressed air circulating around the outside of the conduit.
[0018] Thus there has long been a need for a powder delivery system
which is capable of overcoming the aforementioned disadvantages.
Attempts have been made to improve the respirable fraction of a
powder (FPF) but these generally comprise the use of very low
density particles. For example U.S. Pat. No. 6,254,854 describes
the use of particles with a density of less than 0.4 g cm.sup.-3,
whereas conventional particles in powders administered, e.g. by
inhalation, may have a density of about 0.8 to 1 g cm.sup.3.
[0019] Thus, there is clearly a need for the development of a
device suitable for the delivery of particles of any density, which
provides low powder retention and provides a high respirable dose.
For example, particles of conventional density, or low density
particles as hereinbefore described, or even higher density
particles.
[0020] We have now developed a powder delivery system which may
comprise a number of high efficiency, controllable, elements and
therefore overcomes or mitigates the disadvantages of the prior
art. In particular the powder delivery system of the present
invention overcomes the problem of MDIs by separation of the
propellant volatile fluid and the powder. Furthermore, the powder
delivery system of the invention overcomes the problems associated
with prior art DPI devices and, inter alia, provides a greater
efficiency of aerosolisation. It is therefore especially suited for
use as a portable or hand held delivery device.
[0021] Thus according to a first feature of the invention we
provide an air amplifying system comprising an amplify fluid jet
provided with a fluid inlet and a fluid outlet, the fluid outlet
being linked to an outlet nozzle via an amplifying passage, the
amplifying passage also being linked to a powder chamber, said
chamber being adapted for non-laminar powder flow, such that fluid
travelling from the fluid outlet of the jet draws extraneous air
and aerosolised powder through the powder chamber so that the
extraneous air and aerosolised powder mix with the amplifying fluid
in the amplifying passage and the amplified mixture exits through
the outlet nozzle.
[0022] In particular, the ail amplifying system of the invention
utilises an amplified fluid, e.g. gas, stream to disperse a powder.
An unamplified gas stream can be created which is of sufficient
velocity, for example by passing through an amplifying jet, so
that, as it exits the jet and passes across an amplification
passage, in the form of a first opening of a contiguous powder
chamber or conduit, the gas stream creates a vacuum in the
contiguous chamber or conduit.
[0023] The chamber or conduit can be provided with a powder
reservoir or a powder metering member adjacent au inlet to the
powder chamber, such that the vacuum created by the exit of the gas
stream from the amplifying jet creates a vacuum in the powder
chamber and an entrainment air flow through the powder.
[0024] This entrainment air flow is sufficient to cause
deagglomeration and/or entrainment and then subsequent
aerosolisation of the powder. One effect of the vacuum is to
deagglomerate the powder without direct impingement of the gas
stream on the powder. This may limit impaction of powder and hence
retention of powder within the device which may be a problem with
some prior art devices. Moreover, the gas stream can also be
adapted to be deflected against a solid surface, the effect being
the tendency of the flow to become attached to or flow around the
solid surface. The exploitation of this effect, therefore enables a
`shape` to be given to the existing gas stream. One advantage of
the system of the invention is that, inter alia, it provides a
greater efficiency of deagglomeration and/or aerosolisation over
prior art devices by the direction of the entrained air.
[0025] We have especially found that by influencing the shape of
the gas stream to have a substantially non-laminar motion provides
an improvement in the deagglomeration of the powder reflected in a
significant improvement in respirable or fine particle fraction
(FPF) of the delivered powder aerosol and a reduction in the powder
retention within the device. Furthermore, Computational Fluid
Dynamics (CAD) studies indicate significantly improved fluid
dynamics.
[0026] In a particular preferred embodiment of the invention the
powder chamber is adapted such that the aerosolised powder is
deliberately subjected to a non-laminar flow. Preferentially, the
non-laminar flow may be achieved by the use of an annular powder
chamber. Thus, in particular, the air amplification system of the
invention is provided with an annular powder chamber and an axial
fluid jet.
[0027] Thus, in one embodiment of the invention the powder chamber
may substantially form the body of the amplification system or be
circumferential to the body of the device and the amplifying fluid
jet may be axial to the body. In this particular embodiment the
powder chamber may be a thin annular chamber. Preferably, the thin
annular chamber may be created by bringing together male and female
portions. Therefore, the outlet end of the fluid jet may comprise,
or alternatively, may be fitted to, a frusto conical male member
which fits into an outer portion of the powder chamber, e.g. in the
form of a female member.
[0028] In this embodiment of the invention the separation between
the male and female members may vary. Preferably, the separation
between the male and female members which may be identified as the
clearance may be from 100 to 5000 .mu.m, preferably from 500 to
2000 .mu.m. Most preferably, the clearance may be about 1000
.mu.m.
[0029] Thus, the diameter of the jet may be from 100 to 500 .mu.m,
preferably from 200 to 300 .mu.m, most preferably 250 .mu.m. The
diameter of the nozzle may vary, but may be from 100 to 1500 .mu.m,
preferably from 400 .mu.m to 1200 .mu.m especially from 400 .mu.m
to 600 .mu.m, e.g. 500 .mu.m.
[0030] In the air amplifying system of the invention the dimensions
of the nozzle and jet may vary depending, inter alia, upon the
nature of the powder to be delivered. However, importantly, the
nozzle should possess a greater diameter than that of the diameter
of the jet. This particular aspect of the invention is advantageous
in that as the fluid, e.g. air, leaves the jet through the nozzle
it expands creating a vacuum in the adjacent powder chamber. Thus,
the ratio of the diameter of the jet to the diameter of the nozzle
may vary, but may be in the range of from 1:8 to 1:2, preferably
1:4 to 1:2 and especially 1:2. Furthermore, in the air amplifying
system of the invention the shape of the nozzle may be changed
and/or multiple nozzles may be used to, inter alia, reduce
oropharyngeal deposition. A particular advantage of the present
invention is that, inter alia, the air amplifying system has the
ability to "slow" the aerosol. Conventionally known inhalers
require the use of, for example, a spacer tube to achieve this.
Thus, the air amplifying system cam `slow` the aerosol without the
use of such a spacer tube.
[0031] The powder reservoir and/or metering member may be
contiguous with the powder chamber. Alternatively, the powder
chamber may be connected to the powder reservoir and/or metering
member by one or more conduits.
[0032] The air amplifying system of the invention may be useful in
a variety of situations. However, it is especially useful when
incorporated in a powder delivery device.
[0033] Thus according to a second feature of the invention we
provide a powder delivery device which comprises a delivery
passage, a powder reservoir and/or a metering member adapted to
present a measured dose of powder to the delivery passage
characterised in that the powder delivery device is provided with
an air amplification system as hereinbefore described.
[0034] In a particularly preferred embodiment of the invention, the
air amplifying system creates an entrained air flow through the
powder reservoir and/or metering member. Thus, the powder reservoir
and/or metering member, may be positioned adjacent a powder inlet
and the flow through the amplifying jet is sufficient to draw
entrained air and powder through the inlet. The reservoir and the
metering member may be separate, e.g. a bulk powder reservoir with
a metering member. Alternatively the reservoir and metering member
may comprise a single item, thus, for example, the device of the
invention may be provided with one or a plurality of prefilled
metering members.
[0035] It should be understood that the basis of this aspect of the
present invention is the creation of a pressure differential across
or through the powder reservoir and/or metering member which
enables the deagglomeration of the powder to occur. Therefore, the
creation of a pressure differential may generally comprise the
creation of a vacuum. It is especially preferred that the entrained
air will flow through the powder which is presented either direct
from the reservoir or, preferentially from the metering member.
Thus, preferably, the entrained air inlet will be positioned
adjacent to a first side of the reservoir and/or metering member
and the vacuum is created adjacent a second, opposite side of the
reservoir and/or metering member. In a further embodiment, a
further inlet tube may be provided which is adapted to introduce
entrainment air, e.g. flushing air into the reservoir/metering
member.
[0036] It is further preferred that the entrained air flow is
sufficient to both deagglomerate and aerosolise the powder,
although, as hereinbefore described, inter alia, improved
deagglomeration can be achieved by the use of a non-laminar
entrained air flow.
[0037] The air amplifying system of the invention may be used in
conjunction with a variety of delivery devices. However, the powder
delivery system is especially suited for use in the delivery of a
powdered medicament. Such a system may be used for the delivery of
an type of powdered medicament, but the system finds particular
utility in the delivery of an inhaled medicament. Thus the system
of the invention may be used as or in conjunction with an inhaler,
e.g. a dry powder inhaler.
[0038] Thus according to a preferred aspect of the invention the
powder delivery device of the invention may be an inhaler. We
especially provide a, dry powder inhaler characterised in that it
incorporates a powder delivery device as hereinbefore
described.
[0039] In a further embodiment of the invention the amplification
system may be provided with a plurality of nozzles and/or a
plurality fluid jets. Such a plurality of nozzles and/or jets may
increase the volume of powder which may be drawn the powder
chamber. At the same time the total velocity of the fluid flowing
through the jets and/or exiting through the nozzle. This is
especially advantageous in the case of delivery of a powdered
medicament, e.g. in an inhaler, since it enables a low velocity
aerosolised powder cloud to be generated. In a yet further
embodiment the fluid jet may comprise a plurality of interlocking
jets. In such a case each jet may, optionally, be provided with one
or more powder inlets. Furthermore, the system may be arranged to
provide the separate, sequential or simultaneous operation of the
jets to enable the creation of an aerosolised powder which
coincides with, for example, the inspiration of a patient.
[0040] When the vacuum means comprises a Venturi-type system as
hereinbefore described the pressurised fluid may be any fluid
moving system. The fluid may be a liquid, however, preferentially,
the fluid is a gas, for example, compressed air or a gas/vapour
generated from the volatilisation of a volatile propellant, such as
that delivered from a pressurised canister. Alternatively, the
fluid flow may be generated by an electric motor, e.g. a battery
operated motor, or by a manually primed piston, e.g. a hand
pump.
[0041] When the vacuum means comprises the use of a volatilised
propellant, any conventionally known pharmaceutically and/or
environmentally acceptable propellants may be utilised. Such
propellants include, but are not limited to, non-CFC propellants,
such as a hydrofluoroalkane (HFA). Any conventionally known HFA
propellant may be used, including those disclosed in, for example,
EP0372777, WO91/04011, WO91/11173, WO91/11495 and WO91/14422.
However, the most preferred HFA is a fluoroalkane such as a
fluoromethane or a fluoroethane or a mixture of fluoroalkanes. Such
fluoroalkanes include, but are not limited to,
trichlorofluoromethane, dichlorodifluoromethane,
1,2-dichlorotetrafluoret- hane, trichlorotrifluoroethane and
chloropentafluoroethane. One HFA which may be mentioned is HFA 134
(1,1,1,2-tetrafluoroethane) or HFA 227.
[0042] When the delivery device of the invention is utilised as or
in conjunction with an inhaler, it is especially advantageous
utilisation of entrained air not only deagglomerates the powder but
also helps to facilitate aerosolisation of the powder.
[0043] When the powder delivery device comprises an inhaler, it may
comprise a conventionally known inhaler with a system of the
invention attached thereto. An example of a conventional inhaler is
a CLICKHALER (available from Innovata Biomed in the UK and
described in European Patent application No. 0 539 469) which is
provided with an inhalation passage. The delivery device of the
invention may optionally be attached, for example, at the outlet
end of such an inhaler, to a spacer device.
[0044] In one embodiment, the metering member is adapted to
transfer measured doses of powder from the powder reservoir to the
delivery passage.
[0045] However, in an alternative embodiment, the powder may be
presented to the delivery passage in a closed form, wherein it is
opened in the delivery passage. Thus, the metering member may be a
capsule, in which case the device may optionally be provided with
means for piercing or rupturing the capsule.
[0046] In a yet further and preferred embodiment the powder may be
presented to the delivery passage in an open form. Thus, for
example, the metering member may be a spool carrying a powder, in
which case the device may be provided with means for presenting the
spool, in an open form into the delivery member.
[0047] Thus, the metering member may comprise a spool housed in a
spool carrier. Such spools are generally described in the prior
art. An example of such an inhaler system is a TECHNOHALER
(available from Innovata Biomed in the UK and described in European
Patent Application No. 0 626 689). Each spool has a flange at each
end which form a tight slidable fit within the body of the spool
carrier. The space left between the body of the spool and the spool
carrier is filled with an appropriate powder. In an alternative
embodiment the delivery device may be provided with a spool
chamber, for example, in the form tube adjacent the delivery
passage. In a preferred embodiment the spool chamber may form a
snug fit around the spool and may therefore replace the spool
carrier. The spool chamber may therefore optionally be fitted with
an actuator member which may comprise a push rod mechanism.
[0048] The delivery device of the invention is advantageous in
that, inter alia, it may operate by the administration of a cloud
of powder. The device provides a dry powder delivery system which
is independent of the rate of inspiration of a patient, and without
the need for a patient to inhale undesirable propellants.
[0049] Furthermore, the inhaler of the invention is especially
advantageous in that, inter alia, it may provide a significant
increase in the respirable fraction of a delivered powder. As
hereinbefore described, it is a particular aspect of the inhaler of
the present invention that the inhaler may not require the use of a
spacer, but still be able to "slow" the aerosol.
[0050] A variety of powders may be administered by using the
inhaler of the invention. Such powders are generally drugs for the
treatment of asthma, chronic obstructive pulmonary disease and
respiratory infections. Such powders include, but are not limited
to B.sub.2-agonists, e.g. fenoterol, formoterol, pirbuterol,
reproterol, rimiterol, salbutamol, salmeterol and terbutaline;
non-selective beta-stimulants such as isoprenaline; xanthine
bronchodilators, e.g. theophylline, aminophylline and choline
theophyllinate; anticholinergics, e.g. ipratropium bromide; mast
cell stabilisers, e.g. sodium cromoglycate and ketotifen; bronchial
anti-inflammatory agents, e.g. nedocromil sodium; and steroids,
e.g. beclomethasone dipropionate, fluticasone, budesonide and
flunisolide; and combinations thereof.
[0051] It is within the scope of this invention for two or more
powders to be administered.
[0052] Specific combinations of powders which may be mentioned
include combinations of steroids, such as, beclomethasone
dipropionate, fluticasone, budesonide and flunisolide; and
combinations of to .beta..sub.2-agonists, such as, formoterol and
salmeterol. It is also within the scope of this invention to
include combinations of one or more of the aforementioned steroids
with one or more of the aforementioned .beta..sub.2-agonists.
[0053] Further powders which may be mentioned include systemically
active materials, such as, proteinaceous compounds and/or
macromolecules, for example, hormones and mediators, such as
insulin, human growth hormone, leuprolide and alpha interferon;
growth factors, anticoagulants, immunomodulators, cytokines and
nucleic acids.
[0054] It is within the scope of this invention to include
combinations of any of the aforementioned medicaments.
[0055] The particle size of the powder may be varied depending,
inter alia, on the type of aerosol being formed. In the case of a
dry powder medicament, the particle size of the powder, and the
carrier, if one is present may be varied. The nature of the carrier
may also be varied. Thus, the particle size of the powder may be
substantially between 1 and 100 .mu.m. That is, at least 90% w/w of
the powder should have a particle size of between 1 and 100 .mu.m.
The preferred particle size may also depend upon the nature of the
powder being delivered. Thus, for example, for the treatment of
respiratory disorders a particle size of 4 to 8 .mu.m may be
preferred, e.g. 6 .mu.m.
[0056] However, for the delivery of systematically active powders a
smaller particle size may be desirable, for example from 1 to 5
.mu.m, e.g. 2 .mu.m.
[0057] In a dry powder formulation a variety of carriers may be
used. Certain carriers may be mentioned, by way of example only,
such as sugars, e.g. dextran, mannitol and lactose, for example
.alpha.-lactose monohydrate. The particle size of the carrier may
be across a wide range, between 0.1 and 500 .mu.m, preferably
between 1 and 200 .mu.m. Alternatively, the carrier may itself
comprise a mixture of fine and coarse particles.
[0058] According to a further feature of the invention we provide a
method of administering a medicament which comprises the use of a
powder delivery device as hereinbefore described.
[0059] As previously mentioned the powder delivery device of the
invention is especially suited for use as a medicament delivery
device, e.g. an inhaler. Therefore, we further provide a method of
treatment of a patient with a respiratory disorder which comprises
the administration of a powdered medicament using a device as
hereinbefore described. In an especially preferred embodiment the
method comprises administration of medicament by inhalation.
[0060] In a preferred embodiment we provide a method of treatment
of a patient with a systemic disorder which comprises the
administration of a medicament using an inhaler as hereinbefore
described.
[0061] The device of the invention is especially suited for the
efficient delivery of macromolecules, such as insulin. Thus,
according to a particular feature of the invention we provide a
method of treating insulin dependent diabetes which comprises
administration of an effective amount of insulin using a device as
hereinbefore described.
[0062] When the device of the invention is used for the delivery of
macromolecules, such as insulin, it is important that they be
provided in a moisture resistant system. Thus, according to the
invention we provide a device as hereinbefore described provided
with a moisture resistant coating e.g. a paraxylylene coating.
[0063] The device of the invention is advantageous un that, inter
alia, a significantly increased respirable fraction is achieved. A
conventional inhaler might be expected to deliver a respirable or
fine particle fraction of, for example, 20-40%. However, the
delivery device of the invention is able to provide an FPF of in
excess of 70%.
[0064] The respirable fraction of a powder, known as FPF is
generally a measurement of the percentage of a powder that reaches
the lung of a patient as of function of the delivered dose.
Respirable powder particles are considered to be about 6 .mu.m
(aerodynamic diameter) or less and therefore the FPF value of an
aerosolised powder is a measure of the percentage of particles with
the desired respirable size. A delivery device with a high FPF
value is therefore desirable. Conventionally known DPI's provide an
FPF of about 20-30% w/w.
[0065] One measure of the efficiency of a delivery device is the
difference between the metered dose (MD) and the delivered dose
(DD), conventionally this is known as the retention. Thus, a
delivery device with low retention is desirable. Conventionally
known DPI's provide a powder retention of approximately 10%
w/w.
[0066] Conventionally know DPI's that provide a high FPF will
provide a relatively high powder retention. Alternatively, those
DPI's that provide a low powder retention may provide a relatively
low FPF.
[0067] The delivery device of the invention is advantageous in
that, inter alia, it provides a high APT and a low powder
retention. The achievement of a combined high FPF and low retention
in a dry powder inhaler is novel per se.
[0068] Thus, according to a further aspect of the invention we
provide a powder delivery device characterised in that the delivery
device provides a high FPF and low powder retention.
[0069] In a preferred aspect of the invention the delivery device
of the invention is a dry powder inhaler.
[0070] Thus we especially provide a delivery device as hereinbefore
described which comprises a substantially axial jet and a
substantially annular deagglomeration chamber.
[0071] The dry powder inhaler may therefore provide an FPF of at
least 70% w/w. Preferably, the dry powder inhaler of the invention
may provide an FPF of at least 80% w/w, more preferably at least
90% w/w and most preferably at least 95% w/w. The dry powder
inhaler of the invention may provide a powder retention of less
than 10% w/w, preferably less than 0.5% w/w and most preferably
less than 2% w/w.
[0072] According to a further aspect of the invention we provide a
method of delivery of a powder with a high FPF and low powder
retention as hereinbefore described which comprises the use of a
delivery device comprising an air amplifier.
[0073] According to a further aspect, we provide a method of
treatment of a patient suffering from a respiratory disorder which
comprises the delivery of a medicament powder comprising a high FPF
and low powder retention.
[0074] The invention will now be described by way of example only
and with reference to the accompanying drawings in which:
[0075] FIG. 1a is a schematic cross-section of an air amplifying
system of the invention;
[0076] FIG. 1 is a perspective representation of a single chamber
device of the invention
[0077] FIG. 2 is a perspective representation of a disassembled
single chamber device of the invention;
[0078] FIG. 3 is a cross-sectional representation of a single
chamber device of the invention;
[0079] FIG. 4 is a perspective representation of a multi axial
nozzle device of the invention;
[0080] FIG. 5 is a perspective representation of a disassembled
multi axial nozzle device of the invention;
[0081] FIG. 6 is a cross-sectional representation of a multi axial
device of the invention;
[0082] FIG. 7 is a perspective representation of a multi axial
nozzle device of the invention provided with a plurality of powder
inlets;
[0083] FIG. 8 is a perspective representation of a disassembled
multi axial nozzle device of the invention provided with a
plurality of powder inlets;
[0084] FIG. 9 is a cross-sectional view of a multi axial nozzle
device of the invention provided with a plurality of powder
inlets;
[0085] FIG. 11 is a cut-away perspective representation of a
disassembled multijet device of the invention;
[0086] FIG. 12 is a cross-sectional view of a multijet device of
the invention;
[0087] FIG. 13 is a perspective representation of a multijet device
with individually activatable powder inlets;
[0088] FIG. 14 is a cut-away perspective of a disassembled multijet
device with individually activatable powder inlets; and
[0089] FIG. 15 is a cross-sectional representation of the device of
FIG. 14.
[0090] FIGS. 16a-c are cross-sectional schematic representation of
the system of the invent, illustrating the sequence of operation of
the inhaler;
[0091] FIG. 17 is a system of the invention;
[0092] FIG. 18a is a mathematical model of a static pressure
contour plot throughout the device of the invention;
[0093] FIG. 18b is a mathematical model of a static pressure
contour plot throughout a device of the prior art with main fluid
flow from the side and powder flow through the middle;
[0094] FIG. 19a is a mathematical model of a velocity magnitude
contour plot throughout the device of the invention;
[0095] FIG. 19b is a mathematical model of a velocity magnitude
contour plot throughout a device of the prior art with main fluid
flow from the side and powder flow through the middle;
[0096] FIG. 20a is a mathematical model of the velocity of 5 .mu.m
particles with a coefficient of restitution of 0.25, throughout the
device of the invention;
[0097] FIG. 20b is a mathematical model of the velocity of 5 .mu.m
particles with a coefficient of restitution of 0.25, throughout a
device of the prior art with main fluid flow from the side and
powder flow through the middle;
[0098] FIG. 21a is a mathematical model of the velocity of 5 .mu.m
particles with a coefficient of restitution of 0.75, throughout the
device of the invention;
[0099] FIG. 21b is a mathematical model of the velocity of 5 .mu.m
particles with a coefficient of restitution of 0.75, throughout a
device of the prior art with main fluid flow from the side and
powder flow through the middle;
[0100] FIG. 22a is a schematic representation of the device of the
invention used in the experiment of Example 2; and
[0101] FIG. 22b is a schematic representation of the device of the
prior art, with main fluid flow from the side and powder flow
through the, middle, used in the experiment of Example 2.
[0102] Referring to FIG. 1a, an air amplifying system (1) comprises
a housing (2) and a fluid jet (3) provided with a fluid inlet (4)
and a fluid outlet (5). The fluid outlet (5) is linked to an outlet
nozzle (6) via an amplifying passage (7). The amplifying passage is
also linked to an annular powder flow chamber (8). The powder flow
chamber (8) is adapted to provide a non-laminar flow path for the
powder (not shown). The chamber (8) is also provided with an inlet
(9).
[0103] In use, fluid travelling through the amplifying jet (3)
draws extraneous air through the powder chamber (8) aerosolising
and deaggromerating powder.
[0104] Referring to FIGS. 1 to 3, a powder delivery device (111)
comprises a body portion (112), a powder inlet (113) and powder
outlet (114). The body portion (112) comprises a male member (115)
and a female member (116). The male member (115) is a substantially
cylindrical member provided with a frusto conical region (117) at
one end (118). The second end (119) is provided with an annular
shoulder (120). The shoulder (120) being provided with an annular
recess (121) adapted to receive an annular sealing ring (122). The
male member (115) is provided with an axial fluid flow chamber
(123) provided with an inlet (124) and an outlet (125).
[0105] The female member (116) is adapted to fit over the male
member (115). Thus the female member (116) presents a cavity (126)
which is provided with a frusto conical region (127) adapted to fit
with the frusto conical region (117) of the male member (115). The
region of the cavity (126) dista to the frusto conical region (127)
engages with the shoulder (120) of the male member (115). The end
(128) of the female member (116) is also provided with an annular
recess (129) to receive a portion of the annular sealing ring
(122). Thus, an annular powder dispersion chamber (130) is created
between the male member (115) and the female member (116). The
powder dispersion chamber (130) is provided with an inlet (131) and
an outlet (132), the outlet (132) being coincident with the outlet
(125) of the fluid flow chamber (123) and the outlet (114) of the
female member (116).
[0106] In use, a gas, e.g. air or a volatile propellant passes
along the fluid flow chamber (123), exiting at the outlet (125). At
the junction with the powder dispersion chamber (130). The
Venturi-type effect of the fluid flow creates a vacuum in the
powder dispersion chamber (130) causing air to be drawn in at inlet
(131).
[0107] Referring to FIGS. 4 to 6, a powder delivery device (211)
comprises an annular body portion (212), and an end cap (213). The
end cap (213) is provided with a central aperture (204) which is
coincident with an aperture (215) created in the body portion
(212). The end cap (213) is provided with an annular recess (214)
adapted to receive an annular sealing ring (215). The end cap (213)
is also provided with a frusto conical region (216) which surrounds
the gas inlet aperture (214). The body portion (212) is also
provided with a plurality of annular jet rings (206). Each jet ring
(206) is provided with a hollow frusto conical portion (217) which
surrounds a central jet aperture (218). Due to the hollow region
(219) in a the frusto conical portion (217), the portion acts as a
female member which fits over a male member of the adjacent jet
ring (206).
[0108] Each annular jet ring (206) is provided with a plurality of
spacers (220) to separate one ring from an adjacent ring. The space
(221) between each ring (206) can therefore act as a powder inlet
for powder fed from cavity (222).
[0109] In use, a gas is fed through the inlet aperture (214) which
passes through corresponding jet ring apertures (218). Thus
creating ail increased vacuum in cavity (222). Powder is fed into
cavity (222) and expressed through the jets and exits via aperture
of the end jet (218d).
[0110] Referring to FIGS. 7 to 9, a powder delivery device (311) is
analogous to that illustrated in FIGS. 4 to 6. The body (312) of
the device is provided with a plurality of apertures (314) which
act as powder inlets.
[0111] Referring to FIGS. 10 to 15, a powder delivery device (411)
comprises a body portion (412), a powder inlet (413) ad a plurality
of powder outlets (414). The body portion (412) comprises an
annular wall (415) and end piece (416). The end piece (416) is
provided with a gas inlet (407), an annular shoulder (417) and an
annular recess (418) adapted to receive an annular sealing ring
(419). The end piece (416) is provided with a male member region
(427) which engages with a jet holder (420). The jet holder (420)
is provided with a plurality of jets (421) and is provided with a
recess region (422) and surface (423) facing the end piece (416).
The recess (422) presents a cavity (403) which is beneath the jets
(421). The jets (421) mate with powder outlets (414). Each of the
jets comprises a frusto conical member (424) such that the shoulder
of the cone (425) prevents the body portion (412) from resting
against the jet holder (420) creating a powder delivery chamber
(426).
[0112] In use, a gas, e.g. air or a volatile propellant passes
through the inlet (407) into cavity (403) and through jets (421).
The Venturi-type effect of the fluid flow creates a vacuum in the
powder dispersion chamber (426) causing powder to be drawn in at
inlet (413).
[0113] Referring to FIGS. 16 and 17, a powder delivery system (51)
comprises an axial fluid jet (502) with an out let (503) at one end
(504). The jet (502) is surrounded by an annular powder
deagglomeration chamber (505). The outlet (503) of the jet (502)
meets the deagglomeration chamber (505) and exits the system (501)
at a nozzle (506). The deagglomeration chamber is comprised on a
frusto conical male member (507) and a corresponding female member
(508). The deagglomeration chamber (505) is provided, at one side
(509) with a powder delivery chamber (510).
[0114] The chamber (510) is provided with an inlet (511) and an
outlet (512), at the end of au inlet conduit (513). The outlet
(512) is coincident with an inlet (514) into the deagglomeration
chamber (505). The delivery chamber (510) is also provided with an
air inlet (515) positioned at the end (516) of the delivery chamber
(510) distal to the outlet (512). In use, the inlet conduit (513)
houses a metering spool (517) which carries a powdered medicament
(518).
[0115] Referring to FIGS. 16b and 16c, in use, the powder delivery
system (501) is primed by inserting a spool (517) carrying powder
(518) into the inlet conduit (513). The spool (517) is pushed to
the end of the conduit (513) and into the delivery chamber (510).
Compressed air is applied (see arrow (519)) into the jet (502). Air
flows through the jet (502) and leaves at the outlet (503). The
exiting air creates a vacuum in the deagglomeration chamber (505)
and causes suction in the powder delivery chamber (510).
[0116] The air flow (shown by arrow 520) deagglomerates and
subsequently aerosolises the powder (518) which passes out of the
delivery chamber (510). Fine particles are capable of passing
straight tough the deagglomeration chamber (505) whilst larger
particles collide with the walls of the chamber (505) (and possibly
with each other)) and are deagglomerated to small respirable
particles when they reach the nozzle (506).
[0117] Referring to FIG. 22; in FIG. 22a (Case 1) an air amplifier
of the invention (221), comprises a central, axial jet (222), an
annular powder deagglomeration chamber (223) and a nozzle (224).
The annular deagglomeration chamber being provided with a powder
inlet (225).
[0118] In FIG. 22b (Case 2) an air amplifier of the prior art
(226), comprises a central, axial powder chamber (227), an annular
jet chamber (228) and a nozzle (229). The annular jet chamber (227)
being provided with an air inlet (230).
EXAMPLE 1
[0119] CFD Examination of the Flow
[0120] Objectives of Study:
[0121] To generate a CFD model of the flow of air through two
configurations of the air amplifier of the invention.
[0122] To validate the air flow model by comparison with
experimental data relating to prototype air amplifiers.
[0123] Geometry and Grid
[0124] A mesh was produced in ICEM-CFD using 235590 cells.
Tetrahedral cells were used in the converging cone section of the
geometry. Pentahedral cells were used in the straight pipe sections
to reduce cell numbers over a fully tetrahedral mesh.
[0125] Model Inputs--Continuous Phase
[0126] A constant absolute pressure equal to atmospheric was set at
the outflow boundaries (i.e., a gauge pressure of 0 Pa).
[0127] An ideal gas law was used for the fluid properties to allow
for the compressibility of air at the high Mach numbers
induced.
[0128] The segregated solver was used, along with second-order
upwind discretisation for all variables, and the SIMPLE
velocity-pressure coupling algorithm.
[0129] Standard k-.epsilon. turbulence model was used with viscous
heating.
[0130] Boundary Conditions:
[0131] Case 1: Flow Through Centre, Drug from Side
1 Region Value Turbulent Intensity Length scale Middle inlet 3 Bar
5% 0.0001 m Side inlet 1.735e-5kg/s 5% 0.0001 m Outlet 0 Pa 1%
0.00005 m
[0132] Case 2: Flow from Side, Drug Through Middle
2 Region Value Turbulent Intensity Length scale Middle inlet
1.735e-5kg/s 5% 0.0001 m Side inlet 3 Bar 5% 0.0001 m Outlet 0 Pa
1% 0.00005 m
[0133] Model Inputs--Discrete Phase
[0134] Density of drug particles was set at 800 kg m.sup.-3.
[0135] The total mass flow rate was set to 1.12.times.10.sup.-5
kg/s (equal to 2.8 mg in 0.25 seconds, value supplied by IB).
[0136] The continuous phase and discrete phases were simulated both
as coupled and uncoupled.
[0137] The discrete phase boundary condition at wall surfaces was
set to "reflect" with a coefficient of restitution of 0.25 and
0.75.
[0138] Turbulent interaction between the continuous and discrete
phase was modelled.
[0139] Initial particle speed was set to the average velocity
magnitude over the inflow boundary from which the particles were
released.
[0140] Initial particle of 293K.
[0141] Particle size simulated 5 microns.
[0142] The drag law used for the simulations was the
high-Mach-number drag law to account for the high velocities and
large variations in fluid density seen in the simulations.
[0143] Number of particles tracked was 60 spaced evenly over the
drug inlet boundary.
RESULTS AND CONCLUSIONS
[0144] FIGS. 18a and 18b show a static pressure contour plot from
Case 1 and Case 2 respectively.
[0145] A preliminary CFD study of the section pressure with the
side inlet blocked of to flow showed a negative static pressure of
529 mbar. Experimental results taken at IB give a suction pressure
of 334 mbar on the side inlet with a driving pressure of 3 bar on
the central inlet. This corresponds sufficiently well to the CFD
prediction to proceed with the study of particle trajectories. In
Case 1 the flow through the centre induces a suction pressure of
122 mbar on the side inlet. Thus, as expected, the presence of the
flow through the side inlet changes the pressure distribution.
[0146] Both the CFD and experimental results show that a positive 3
bar pressure on the side inlet does not induce a suction pressure
on the central inlet. Thus, in Case 2 a positive pressure on the
central inlet is needed to induce the correct mass flow rate (to
allow comparison between the two cases).
[0147] FIGS. 19a and 19b show a velocity magnitude contour plot
from Case 1 and Case 2 respectively.
[0148] As expected, in Case 1 the highest velocity (>500 m/s)
occurs when the flow expand as it leaves the smallest diameter pipe
through the middle of the device and corresponds to the region
where the air density is at its lowest.
[0149] In Case 2 the highest velocity seen is smaller (>300 m/s)
and is in the outlet section of the device. There is no point where
the flow is accelerated sufficiently for the density of the air to
decrease below its value at standard temperature and pressure,
unlike Case 1. It is the expansion of air in Case 1 that drives the
larger velocities.
[0150] FIGS. 20a and 20b show the trajectories of 5 micron
particles from Case 1 and Case 2 respectively when a coefficient of
restitution of 0.25 is used 5 micron particles have small enough
inertia that they are strongly effected by local air speeds.
[0151] In Case 1 particles are thrown out to the outside of the
converging vortex section and are then entrained into the boundary
layers of the exit flow. Turbulent eddies can knock the
trajectories nearer into the middle of the flow but they tend to
follow the outside of the exiting flow.
[0152] In Case 2 the small inertia of the particles mean that they
largely follow the flow and do not collide with the wall surfaces.
The particle trajectory simulations suggest that wall collisions
are limited to the converging section of the "(central) drug inlet"
and the outlet section.
[0153] FIGS. 21a and 21b show the trajectories of 5 micron
particles from Case 1 and Case 2 respectively when a coefficient of
restitution of 0.75 is used. The coefficient change has little
effect on the overall results from Case 2 because the particles do
not often collide with the walls. In Case 1 the coefficient change
results in less momentum being lost at each collision in the
converging annulus section. Thus the particles have enough momentum
to remain in the rotating flow for longer. They are drawn down into
the converging section where eventually they are entrained into the
main flow and through the outlet.
[0154] N.B. The image shows only 2 of the 12 particles tracked for
the image exiting the outlet. This is because the files produced
when the particles remain bouncing around the domain are very
large, therefore they are truncated for speed.
EXAMPLE 2
[0155] FPF aud FPD Measurements
[0156] Method
[0157] The objectives of the test were to assess and record the
performance of two main variants of the air amplifier system based
on evaluation of the fine particle fraction (FPF) and the powder
pick-up or delivered dose (DD) and to access any blockage
characteristics of the systems, if any. The test work required the
use of a steel amplifier system according to FIG. 22 manufactured
at IB Tewkesbury to enable precise and controlled setting of the
geometries and orientations of the system. In addition plastic
injection moulded components of the variants were manufactured from
the same facility and tested in the similar using a similar
protocol. Air amplifier variants were tested using a spray dried
leucine preparation to represent the powder characteristics of a
typical formulation for systemic drug delivery via the lung. FPF
and DD were determined gravimetrically using a modified glass twin
impinger apparatus. Bach variant was tested using a two second
pulse of air with feed pressures of 5.7 and 3 bar. The two key
amplifier system variants were those which delivered powder through
the "non linear, conical" side passage (the preferred embodiment
denoted A (or Case 1 in the CFD study)) ad a variant B (or Case 2
in the CFD study) which delivered powder through the "linear
central passage". The results are illustrated in Table 1.
3TABLE 1 Nozzle Feed Offset Jet Dia. Dia. Press. Average Average
FPD FPF Variant (mm) (.mu.m) (.mu.m) (bar) MID (mg) DD (mg) (mg)
(%) A 1.0 250 500 5.7 1.04 1.04 0.74 71.2% A 1.0 250 500 5.7 1.16
1.16 0.82 70.7% B.sub.5* 0.1 500 500 3.0 -- -- -- -- B.sub.5* 0.1
500 500 5.5 -- -- -- -- B.sub.65 0.1 500 650 3.0 1.04 1.04 0.38
36.5% B.sub.65 0.1 500 650 5.5 1.12 1.12 0.39 34.8% B.sub.75 0.1
500 750 3.0 1.1 1.1 0.37 33.6% B.sub.75 0.1 500 750 5.5 1.14 1.14
0.43 37.7% B.sub.85 0.1 500 850 3.0 1.22 1.22 0.48 39.3% B.sub.85
0.1 500 850 5.5 0.92 0.92 0.37 40.2% *No FPD or FPF-nozzle
blocked
* * * * *