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Title: Device constituting a powder Air-razor
Abstract: A device and an arrangement are disclosed, which create a powder Air-razor, which into an inhalation air volume de-aggregates and disperses a finely divided medication powder. The powder is generally loaded onto a dosing member intended for use with an inhaler. By sucking air through a mouthpiece connected to a nozzle, particles of the load of powder are gradually de-aggregated, dispersed and continuously released into the sucked air during a defined interval. The gradual de-aggregation and dispersal of the medication powder is generated by a relative motion introduced between the nozzle and the dosing member. The powder is generally loaded onto a larger area than the area of the air nozzle inlet. The nozzle may be positioned outside the dose area until an air stream has begun to flow into the nozzle by suction of air in an inhaling operation.
Patent Number: 6,892,727 Issued on 05/17/2005 to Myrman
| Inventors:
|
Myrman; Mattias (Stockholm, SE)
|
| Assignee:
|
Mederio AG (Hergiswil, CH)
|
| Appl. No.:
|
134474 |
| Filed:
|
April 30, 2002 |
Foreign Application Priority Data
| Current U.S. Class: |
128/203.15; 128/203.19 |
| Intern'l Class: |
A61M 015/00 |
| Field of Search: |
128/20021,200.24,200.23,203.12,202.21,203.13,203.14,203.15,203.18,203.19,203.21,20411-20413
604/58
424/46
222/146.1,146.3,190
|
References Cited [Referenced By]
U.S. Patent Documents
| 5113855 | May., 1992 | Newhouse.
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| 5161524 | Nov., 1992 | Evans.
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| 5349945 | Sep., 1994 | Wass et al.
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| 5388572 | Feb., 1995 | Mulhauser et al.
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| 5408994 | Apr., 1995 | Wass et al.
| |
| 5469843 | Nov., 1995 | Hodson.
| |
| 5655523 | Aug., 1997 | Hodson et al.
| |
| 5694920 | Dec., 1997 | Abrams et al.
| |
| 5823182 | Oct., 1998 | Van Oort.
| |
| 5829434 | Nov., 1998 | Ambrosio et al.
| |
| 5952008 | Sep., 1999 | Backstrom et al.
| |
| 6074688 | Jun., 2000 | Pletcher et al.
| |
| 6245339 | Jun., 2001 | Van Oort et al.
| |
| 6298847 | Oct., 2001 | Datta et al.
| |
| 6397840 | Jun., 2002 | Chrai et al.
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| 6422236 | Jul., 2002 | Nilsson et al.
| |
| 6439227 | Aug., 2002 | Myrman et al.
| |
| 6524557 | Feb., 2003 | Backstrom et al.
| |
| 6591833 | Jul., 2003 | Datta et al.
| |
| 6651341 | Nov., 2003 | Myrman et al.
| |
| 6668826 | Dec., 2003 | Myrman.
| |
| 6681768 | Jan., 2004 | Haaije de Boer et al.
| |
| 2004/0069303 | Apr., 2004 | Brown et al.
| |
| Foreign Patent Documents |
| 0 069 715 | Jan., 1983 | EP.
| |
| 0 414 536 | Feb., 1991 | EP.
| |
| 0134233 | May., 2001 | WO.
| |
| 0224264 | Mar., 2002 | WO.
| |
Primary Examiner: Bennett; Henry
Assistant Examiner: Mitchell; Teena
Attorney, Agent or Firm: Young & Thompson
Claims
1. A device for de-aggregating and into air dispersing particles of a finely
divided dry medication powder loaded onto a substrate member, the powder made available
for inhalation by means of a dry powder inhaler, wherein
the device, referred to as a powder Air-razor, has a nozzle with a nozzle outlet
and a nozzle inlet and a nozzle inlet aperture positioned adjacent to the available
powder;
a suction of air, when applied to the nozzle outlet, creates a local, high velocity
air stream into said nozzle inlet aperture and out through said nozzle outlet;
a relative motion, when introduced between the nozzle and powder onto the substrate
member, is arranged such that the nozzle inlet, and the local, high velocity air
stream going into the nozzle inlet aperture, traverses the available medication
powder, thereby amounting to a powder Air-razor in releasing and dispersing the
powder;
particle aggregates within the finely divided medication powder are de-aggregated
by being subjected to shearing stresses, inertia and turbulence of air in the local,
high velocity air stream going into said nozzle inlet aperture, whereby the particles
of the finely divided medication powder are gradually dispersed into the air as
available powder is gradually accessed by the local, high velocity air stream of
the powder Air-razor when the nozzle and the powder are moved in relation to each
other.
2. The device according to claim 1, wherein at least 40% of the medication powder
mass loaded onto said substrate member is dispersed as fine particles in the inhaled
air stream leaving the nozzle, said fine particles having an aerodynamic diameter
equal to or less than 5 μm.
3. The device according to claim 1, wherein an area of the nozzle inlet is of
the same order as, or smaller than an aggregate area occupied by the finely divided
dry medication powder onto the substrate member; and
said relative motion of the nozzle is arranged such that the nozzle inlet covers
the aggregate area occupied by the finely divided dry medication powder in one
or more traversing steps.
4. The device according to claim 1, wherein an aperture curvature of said nozzle
inlet is given a suitable shape providing a best possible compromise between an
objective of achieving maximum shear stress in the airflow into the nozzle inlet
and an objective of minimizing particle loss due to retention in the nozzle.
5. The device according to claim 1, wherein the finely divided dry medication
powder loaded onto said substrate member in order to be released constitutes a
metered dose.
6. The device according to claim 1, wherein a timing for said relative motion
of the nozzle is adjustable within a time frame of the suction of air taking place.
7. The device according to claim 1, wherein a time interval in a range of 0.01
to 5 s for said relative motion of the nozzle is pre-defined from a start position
to an end position within a time frame of the suction of air taking place.
8. The device according to claim 1, wherein a usable pressure drop by the suction
of air is in a range of 1-8 kPa and more preferably in a range of 1-4 kpa.
9. The device according to claim 1, wherein at least one finely divided medication
powder is loaded onto a first or a second side or onto both sides of said substrate member.
10. The device according to claim 9, wherein the finely divided medication powder
loaded onto a first and second side of said substrate member comprises a first
medication powder onto the first side of the substrate member and a second, different
medication powder onto the second side of the substrate member.
11. The device according to claim 9, wherein said substrate member is porous
or perforated, such that the nozzle, if positioned at the first side, can suck
powder, if present, off the first side and powder, if present, on the second side
off the second side through pores or perforations of the substrate member, such
that powder from the first and the second side, if available on either or both
sides, will get sucked into the nozzle by the suction of air.
12. The device according to claim 1, wherein a defined level of low-pressure
from the suction is required to trigger an air-flow into the nozzle, thereby ensuring
that the resulting air speed is sufficiently high to generate a necessary powder
Air-razor effect.
13. A device for de-aggregating and dispersing into air particles of a finely
divided dry medication powder deposited in an electrostatic or electro-dynamic
field deposition process, or combinations thereof, onto a substrate member, an
individual amount of powder being intended for inhalation by means of a dry powder
inhaler, wherein
the device, referred to as a powder Air-razor, has a nozzle with a nozzle outlet
and a nozzle inlet and a nozzle inlet aperture positioned adjacent to the individual
amount of powder;
a suction of air, when applied to the nozzle outlet, creates a local, high velocity
air stream into the nozzle inlet aperture and out through the nozzle outlet;
a relative motion introduced between the nozzle and powder onto the substrate
member, is arranged such that the nozzle inlet and the local, high velocity air
stream going into the nozzle inlet aperture, traverse the individual amount of
medication powder, thereby amounting to a powder Air-razor in releasing and dispersing
the powder;
particle aggregates within the finely divided medication powder are de-aggregated
by being subjected to shearing stresses, inertia and turbulence of air in the local,
high velocity air stream going into the nozzle inlet aperture, whereby the particles
of the finely divided medication powder are gradually dispersed into the air as
the individual amount of powder is gradually accessed by the local, high velocity
air stream of the powder Air-razor when the nozzle and the powder are moved in
relation to each other.
14. The device according to claim 13, wherein at least 40% of the medication
powder mass loaded onto the substrate member is dispersed as fine particles in
the inhaled air stream leaving the nozzle, said fine particles having an aerodynamic
diameter equal to or less than 5 μm.
15. The de-aggregating and dispersing device according to claim 13, wherein
an area of the nozzle inlet is of the same order as, or smaller than an aggregate
area occupied by the medication powder onto the substrate member;
the relative motion of the nozzle being arranged such that the nozzle inlet will
cover the aggregate area occupied by the finely divided dry medication powder in
one or more traversing steps.
16. The device according to claim 13, wherein the finely divided dry medication
powder loaded onto the substrate member in order to be released constitutes a metered dose.
17. The device according to claim 13, wherein a timing for the relative motion
of the nozzle is adjustable within a time frame of the suction of air taking place.
18. The device according to claim 13, wherein a time interval in a range of 0.01
to 5 s for the relative motion of the nozzle is pre-defined from a start position
to an end position within a time frame of the suction of air taking place.
19. The device according to claim 13, wherein a usable pressure drop by the suction
of air is in a range of 1-8 kPa and more preferably in a range of 1-4 kpa.
20. The device according to claim 13, wherein at least one finely divided medication
powder is deposited onto a first or a second side or onto both sides of the substrate member.
21. The device according to claim 20, wherein the finely divided medication powder
deposited onto a first and second side of the substrate member comprises optionally
different medicament powders, a first medication powder onto the first side of
the substrate member and a second medication powder onto the second side of the
substrate member.
22. The device according to claim 20, wherein the substrate member is porous
or perforated, such that the nozzle, if positioned at the first side, can suck
powder, if present, off the first side and powder, if present, on the second side
off the second side through pores or perforations of the substrate member such
that powder from the first and the second side, if available on either or both
sides, will get sucked into the nozzle by the suction of air.
23. The device according to claim 13, wherein a defined amount of low-pressure
from the suction is required to trigger an air-flow into the nozzle, thereby ensuring
that the resulting air speed is sufficiently high to generate a necessary powder
Air-razor effect.
24. An arrangement for de-aggregating and into air dispersing particles of a
finely divided dry medication powder, comprising a nozzle having a nozzle inlet
and a nozzle outlet and a finely divided dry medication powder made available for
a release, the powder being intended for inhalation by means of a dry powder inhaler, wherein
a suction of air is applied to the nozzle outlet, thus creating a local, high
velocity air stream into a nozzle inlet aperture and out through the nozzle outlet;
a relative motion, when introduced between the nozzle and powder, is arranged
such that the powder is made available adjacent to the nozzle inlet gradually,
while suction is still applied, thus making the local high velocity air stream
release and disperse the powder gradually;
particle aggregates within the finely divided medication powder are de-aggregated
by being subjected to shearing stresses, inertia and turbulence of air in the local,
high velocity air stream going into the nozzle inlet aperture, whereby the particles
of the finely divided medication powder are gradually dispersed into the air as
available powder is gradually accessed by the local, high velocity air stream when
the nozzle and an amount of powder are moved in relation to each other.
25. The arrangement according to claim 24, wherein the arrangement comprises
an Air-razor device.
26. The arrangement according to claim 24, wherein at least 40% of the available
powder mass is dispersed as fine particles in the inhaled air stream leaving the
nozzle, said fine particles having an aerodynamic diameter equal to or less than
5 μm.
27. The arrangement according to claim 24, wherein the finely divided dry medication
powder made available for a release constitutes a metered dose.
28. The arrangement according to claim 24, wherein the finely divided dry medication
powder is made available for a release by means of a moving substrate member or
a vibrating element or a gravitation feeder, or a screw feeder or a conveyor feeder
or a pneumatic tube feeder.
29. The arrangement according to claim 24, wherein a timing for the relative
motion of the nozzle is adjustable within a time frame of the suction of air taking place.
30. The device according to claim 24, wherein a time interval in a range of 0.01
to 5 s for the relative motion of the nozzle is pre-defined from a start position
to an end position within a time frame of the suction of air taking place.
31. The arrangement according to claim 24, wherein a usable pressure drop by
the suction effort is set in a range of 1-8 kPa and more preferably in a range
of 1-4 kPa.
32. The arrangement according to claim 24, wherein a defined amount of low-pressure
from the suction is required to trigger an air-flow into the nozzle, thereby ensuring
that the resulting local, high velocity air speed is sufficiently high to generate
a necessary powder Air-razor effect.
Description
TECHNICAL FIELD
The present invention relates to a device and an arrangement constituting a powder
Air-razor for de-aggregating and into air dispersing finely divided dry medication
powder, made available for a release and intended for inhalation through a dry
powder inhaler device.
BACKGROUND
The dosing of drugs is carried out in a number of different ways in the medical
service today. Within health-care, there is a rapidly growing interest in administering
locally or systemically acting medication in prescribed doses of powder directly
to the airways and lungs of a patient by means of an inhaler in order to obtain
an effective, quick and user-friendly administration of such drugs.
A dry powder inhaler, DPI, represents a device intended for administration of
doses
of powder into the deep and/or upper lung airways by oral inhalation. However,
deep lung deposition of medicament is a more difficult proposition and has only
recently come into focus. Most inhalers on the market today are designed for treatment
of ailments in the airways or local lung, like asthma, where the objective often
is local, not deep lung, deposition. When the objective is a systemic delivery
of the medication, then a deep lung deposition of the powder is preferred and usually
necessary for maximum efficiency. The deep lung is defined as the peripheral lung
and alveoli, where direct transport of a substance to the blood can take place.
If a particle is to reach into the deep lung the aerodynamic particle size should
typically be less than 3 μm, and for a local lung deposition, typically about
5 μm. Larger particle sizes will easily stick in the mouth and throat. Thus,
regardless of whether the objective is a local or systemic delivery of a drug,
it is important to keep the particle size distribution of the dose within tight
limits to ensure that a high percentage of the dose is actually deposited where
it will be most effective.
Particle size is especially important for a successful delivery to the deep
lung upon inhalation. Furthermore, for optimal results, the inspiration must take
place in a calm manner to decrease air speed and thereby reduce deposition by impaction
in the upper respiratory tracts. The advantages of using the inhalation power of
the user to full potential in a prolonged, continuous dose delivery interval within
the inhalation cycle is disclosed in our Swedish Patent no. SE 9904081-8 (WO 01/34233
A1), which is hereby incorporated herein by reference, in its entirety. The patent
presents several devices for efficient distribution of pharmaceutical compositions
in fine powder form in the inspiration air, without using other sources of energy
than the power of the air in the user's inhalation.
Powders for inhalation have a tendency of aggregating, in other words to
clod or to form smaller or larger lumps of particles, which then have to be de-aggregated
before the particles enter into the mouth of the user. De-aggregating is defined
as breaking up aggregated powder by introducing energy; e.g. electrical, mechanical,
pneumatic or aerodynamic energy. To succeed with systemic delivery of medication
powders by inhalation to the deep lung, it is important to achieve a high degree
of de-aggregation of the medication powder in the inhaled air. In most cases, treatment
of a patient is not a single occurrence, but has to be repeated and in some chronic
cases, treatment has to be on a continuous basis. In all cases, de-aggregation
must be very repeatable and dosing must be kept within tight tolerances from one
administration to the next.
A majority of dry powder inhalers of today presents rather moderate deaggregation
capacity. Current inhalation devices intended for asthma and other lung diseases
normally deliver the dispensed drug particles in a larger size range than optimal
for deep lung deposition. This is often caused by inadequate de-aggregation of
powder particle aggregates with a primary particle size in the range 2-3 μm.
Thus, the inhaled dose consists of aggregates of smaller particles. This entails
several disadvantages:
- The uniformity of aerodynamic particle size distribution between different
doses may vary considerably, because the de-aggregation is sensitive to slight
differences in inspiration conditions from one inhalation to the next.
- Particle size distribution of the delivered dose may have a tail of
big aggregates, which will deposit in the mouth and upper airways.
- Retention of the substance in the inhaler may vary with the aerodynamic
particle size distribution and may hence be difficult to control and predict.
Thus, for a consistent, predictable and repeatable delivery of medicaments
to the lungs there is a need of a de-aggregating system capable of producing reproducibly
a very high degree of de-aggregation of the dry powder medicament. This is especially
true for systemically acting drugs, where a deep lung deposition is normally required.
In addition, for locally acting medicaments, where usually a local lung deposition
is preferred, a high degree of de-aggregation of the medication powder is an advantage.
Preferably, the de-aggregating system ought to be insensitive as far as possible
to the inhalation effort produced by the user, such that the delivered aerodynamic
particle size distribution in the inhaled air is independent of the inhalation
effort. The average aerodynamic particle size, which influences the deposition
pattern in the lungs, can be controlled by controlling the primary particle size
distribution of the particles constituting the powder.
Introducing special devices as for example spacers and/or external sources
of energy to amplify the inhalation energy provided by the user during the act
of inhalation are common methods in prior art inhalers for improving the performance
in terms of de-aggregation and dosing predictability and repeatability. The addition
of external sources of energy leads to more complex and expensive inhalers than
necessary, besides increasing the demands put on the user in maintaining the inhaler.
Over the years, many methods and devices have been tried in order to improve
the performance of drug delivery systems based on inhalation. For instance, U.S.
Pat. No. 480,505, dated as early as Aug. 9, 1892, describes a nasal respirator
device, including reticulated material and adapted to receiving a porous medium
impregnated with medicine. Nets, screens or membranes with interstices are well
known to a person skilled in the art, as components in many inhaler designs, either
as carriers of drugs or elements to facilitate the release of the dose to a user.
An example of a prior art inhaler device using a perforated membrane as a dispensing
element for an active compound of medicament is disclosed in a European patent
EP 0 069 715 B1 with priority date Aug. 7, 1981. The patent teaches an inhaler
comprising a nozzle, an air conduit and a displaceable dispensing element in the
form of a perforated membrane, for dispensing the medicament from a storage chamber
into the air conduit. Dry powder inhaler medicament carriers with interstices for
enhancement of de-aggregation of a powder dose are dealt with in several later
documents e.g. U.S. Pat. Nos. 5,388,572; 5,388,573; 5,460,173; 5,647,347; 5,823,182;
6,245,339 B1 and WIPO publication Nos. WO94/20164; WO98/04308. The carriers and
methods, taught in the referred documents, are characterized in that the powdered
medicament is impregnated or embedded in and across interstices at spaced locations
in the carrier, thus forming one or more doses of medicament. A dose is then put
in a flow channel connected to a mouthpiece. As the user inhales through the mouthpiece
the created air stream forces the aggregated dry powder particles of the dose loaded
onto or into the carrier to be released into air and de-aggregated by the shearing
force of the air as it passes through the interstices and past the aggregated powder
particles. Thus, a main purpose of the net or screen type of carrier presented
in the referred documents is to facilitate de-aggregation of the dose. However,
examples in some of the documents show pressure chambers or similar means for creating
a high-pressure air pulse, 70 psig (=490 kPa) in one case, necessary to blow the
dose off the carrier. A pressure of 70 psig is about 100 times higher than the
pressure drop produced by the inhalation of a user. A normal inspiration by an
adult produces about 5 kPa and an external energy source is therefore necessary
in order to produce the air pulse. The suggested methods seem to be limited in
terms of dose mass, only being suitable for rather small doses. The teachings also
suggest using ordered mixtures of active substance and some excipient, to further
improve de-aggregation, which further limits the active medicament mass in the dose.
Another example of an inhalation device addressing the problem of de-aggregation
is disclosed in U.S. Pat. No. 5,694,920 and further improvements of the inhaler
are disclosed in U.S. Pat. Nos. 6,026,809 and 6,142,146. The inventions teach that
de-aggregation of a medication powder may be provided by a vibrator, which directly
or indirectly imparts mechanical energy of suitable frequency and power to the
powder. The powder is thus fluidized and de-aggregated. Particles of a size suitable
for inhalation are then lifted out from the fluidized powder and introduced in
an air stream by an electric field of suitable strength established across the
air stream. The particles are then delivered to a user by the air stream. Clearly,
it is necessary to provide external power in electro-mechanical form to achieve
de-aggregation, which still seems to be only partially successful.
Prior art methods achieving a high de-aggregation and dispersal into air of
a dry medication powder seem to require high levels of de-aggregating power, which
lead to more or less complicated inhaler designs.
SUMMARY
The present invention discloses a device and an arrangement for efficient de-aggregation
and dispersal into air of a finely divided medication powder. In contrast to prior
art the present invention does not require other sources of energy besides the
power of the inhalation effort by the user to produce a very high degree of de-aggregation
and efficient dispersal into air of a dry powder.
A device and an arrangement are disclosed, which provide a powder Air-razor for
de-aggregating and into air dispersing a finely divided medication powder. Utilizing
an effort of sucking air through a nozzle, the particles in the powder, made available
to the nozzle, are gradually de-aggregated and dispersed into a stream of air entering
the nozzle. The gradual de-aggregation and dispersal will be produced by a relative
motion introduced between the nozzle and the powder. In a preferred embodiment
the powder is deposited onto a substrate, the accumulated powder occupying a larger
area than the area of the nozzle inlet. The nozzle is preferably positioned outside
the powder area, not accessing the powder by the relative motion until the air
stream into the nozzle, created by the suction, has passed a threshold flow speed.
Coincidental with the application of the suction or shortly afterwards the relative
motion will begin such that the nozzle traverses the load of powder gradually.
The high velocity air going into the nozzle inlet provides plenty of shearing stress
and impact energy as the flowing air hits the leading point of the border of the
contour of the accumulated powder. This powder Air-razor effect, created by the
shearing stress and the impact of the air stream, is so powerful that the particles
in the particle aggregates in the powder adjacent to the inlet of the moving nozzle
are released, de-aggregated to a very high degree as well as dispersed and subsequently
entrained in the created air stream going through the nozzle.
A powder Air-razor device for de-aggregating and dispersing a metered dose according
to the present invention is set forth by the independent claims 1, 13,
and 24 and further embodiments are defined by the dependent claims 2
to 12, 14 to 23 and 25 to 32.
SHORT DESCRIPTION OF THE DRAWINGS
The invention, together with further objects and advantages thereof, may best
be understood by referring to the following detailed description taken together
with the accompanying drawings, in which:
FIG. 1a illustrates an embodiment of the powder Air-razor device in a
start position;
FIG. 1b illustrates an embodiment of the powder Air-razor device in a
powder releasing phase;
FIG. 2a illustrates another embodiment of the powder Air-razor device
in a start position;
FIG. 2b illustrates another embodiment of the powder Air-razor device
in a powder releasing phase;
FIG. 3a illustrates yet another embodiment of the powder Air-razor device
in a start position;
FIG. 3b illustrates yet another embodiment of the powder Air-razor device
in a powder releasing phase;
FIG. 4a illustrates yet another embodiment of the powder Air-razor device
in a start position;
FIG. 4b illustrates yet another embodiment of the powder Air-razor device
in a powder releasing phase;
FIG. 5 illustrates a medication powder being released, de-aggregated, dispersed
and entrained in air by a powder Air-razor device;
FIG. 6 illustrates a substrate member with a load of powder onto it and a nozzle
with an elliptical inlet aperture;
FIG. 7 illustrates an embodiment of a powder Air-razor device and a dosing member
in a loaded state before release;
FIG. 8 illustrates an embodiment of a powder Air-razor device and a dosing member
just after starting of a release of the powder dose;
FIG. 9 illustrates an embodiment of an inhaler comprising a powder Air-razor
device and a dosing member;
FIG. 10 illustrates an embodiment of a nozzle inlet opening and the air speed
pattern developing during an applied suction effort;
FIG. 11 illustrates the different forces acting on a stationary particle situated
in a stream of air;
FIG. 12 illustrates fluid velocity as a function of distance to an object for
laminar and turbulent flows and
FIG. 13 illustrates the number of particles released into air as a function
of time.
DESCRIPTION
The present invention discloses a powder Air-razor device for de-aggregating
and dispersing into air a dry medication powder. The invention teaches that finely
divided dry medication powder may be delivered to a user with an extremely high
degree of de-aggregation of the powder. The invention presents a powder Air-razor
device and an arrangement to achieve the stated objective.
An important element of the Air-razor device is a relative motion between a nozzle
and a powder. In the document the term "relative motion" refers to the non-airborne
powder in more or less aggregated form being gradually moved, relatively speaking,
by the motion into close proximity to said nozzle, where de-aggregation and dispersal
into air of individual powder particles may take place, provided by the Air-razor.
The term does not refer to airborne powder particles already entrained in air.
Therefore, the mentioning of "motion" or "moving" in relation to "powder" refers
to the contour of powder before the powder particles are released and dispersed
into air.
The medication powder comprises one or more pharmacologically active substances
and optionally one or more excipients. In the document the terms "powder" or "medication
powder" are used to signify the substance in the form of dry powder, which is the
subject of de-aggregation and dispersal into air by the disclosed invention and
intended for deposition at a selected target area of a user's airways. Optional
excipients may or may not de-aggregate in a similar way as the active pharmacological
substance, depending on the design of the powder. For example, an ordered mixture
comprises an excipient characterized by particles considerably larger than those
of the pharmacologically active substance.
A preferred embodiment of the invention is illustrated in FIG. 1a, showing
in a sectional view A—A an example of a medication powder 180 deposited
onto the surface of a substrate member 141 and on the same side of the substrate
member as the powder, a nozzle 1 in a starting position before the powder
is released. FIG. 1b illustrates the nozzle moving in relation to the substrate
member, showing how the powder 180 is being released, de-aggregated and
dispersed into air 20 from the surface of the substrate member 141
by a stream of air hitting the powder before going into the inlet aperture of the
moving nozzle, epitomizing a powder Air-razor device.
Another embodiment is illustrated in FIG. 2a, showing in a sectional
view A—A an example of a medication powder 180 deposited onto the
surface of a perforated substrate member 140 and on the same side of the
substrate member as the powder, a nozzle 1 in a starting position before
the powder is released. FIG. 2b illustrates the nozzle moving relative to
the substrate, showing how the powder is being released, de-aggregated and dispersed
into air 20 from the surface of the substrate member by a stream of air
first going through the perforations, then via the powder and into the inlet aperture
of the moving nozzle, epitomizing a powder Air-razor device.
Yet another embodiment of the powder Air-razor device is illustrated in FIG.
3a similar to FIG. 2a but with the powder 180 deposited underneath
the substrate and a nozzle 1, adjacent to the upper opposite side of the
substrate member 140 as the powder, in a starting position before the powder
is released. FIG. 3b illustrates the powder as it is being released, de-aggregated
and dispersed from the surface of the substrate member by a stream of air going
through the perforations and into the inlet aperture of the moving nozzle, relatively
speaking, on the opposite side of the substrate member as the powder; the moving
nozzle thus epitomizing a powder Air-razor device. Yet another embodiment of the
powder Air-razor device is illustrated in FIG. 4a similar to FIGS. 2a
and 3a showing a medication powder deposited onto both surfaces,
180A and 180B, of a perforated substrate member 140. A nozzle
1 at side 180A is in a starting position before the powder is released.
FIG. 4b illustrates a stream of air accessing the powder on the side 180B,
then going through the perforations and accessing the powder on the side 180A
before going into the inlet aperture of the nozzle, in a relative motion, epitomizing
a powder Air-razor device.
FIG. 5 illustrates in a sectional view A—A a detailed example of a medication
powder deposited onto the surface of a substrate member and a nozzle performing
a relative motion, epitomizing a powder Air-razor device as the powder is being
released, de-aggregated, dispersed and entrained in air.
FIG. 6 illustrates in a top view a substrate member 141 with a load of
powder 180 onto it and a nozzle 1 with an elliptical inlet aperture
3 and in a sectional view A—A the substrate member, powder and nozzle
before the nozzle 1 has begun its relative motion in the direction of the
powder 180.
FIG. 7 illustrates an embodiment of a powder Air-razor device in an inhaler
context, showing a dosing member 4 comprising six substrate members 140
or 141 each provided with a metered dose of powder 180. A nozzle
1, part of a suction tube 33 and a dosing member 4 with one
of the substrate members 140 or 141 are in positions for releasing
an amount of powder. When a spring 9 releases (release mechanism not shown
here but is indicated in FIG. 9) the dosing member 4, it is put in motion
bringing the substrate member 140 (141) and including the powder
180 past the nozzle 1. An airbrake 22 controls the speed of
the dosing member and thereby the release interval of the powder 180, which
is gradually sucked up by an air stream 20 (not illustrated) going into
the nozzle 1 because of suction applied to the suction tube 33. A
foil cutter 11 may optionally be positioned in front of the nozzle, such
that if the dose is protected by a foil, this will be first cut open and folded
away to give the nozzle full access to the powder.
FIG. 8 illustrates the powder Air-razor in action, i.e. how the powder 180,
deposited onto one of the substrate members 140 or 141, is gradually
accessed by the nozzle 1 and the air stream (not illustrated) as the dosing
member and the suction tube 33 are put in a relative motion to each other.
FIG. 9 illustrates an embodiment of an inhaler 8 comprising a powder
Air-razor device, a dosing member 4 comprising one or more substrate members
140 or 141 each provided with a metered dose of powder 180
to be administered sequentially to a user. A breath-actuation mechanism 16,
lets air in and releases a catch 12 holding the dosing member (the loading
and the complete releasing mechanisms are not shown) when the suction applied to
a mouthpiece 19, in fluid connection with the suction tube 33, is
sufficiently strong.
Theoretical Background to the Concept of a Powder Air-Razor Device
Adhesion of Particles
Particles adjacent to other particles or to a substrate member will adhere
to each other. Many different types of adhesive forces will play roles in the total
adhesive force between a particle and the environment, whether another particle,
an aggregate of particles, a substrate member or a combination thereof. The types
of adhesive forces acting on a particle can be van der Waal forces, capillary forces,
electrical forces, electrostatic forces, etc. The relative strengths and ranges
of these forces vary with e.g. material, environment, size and shape of the particle.
The sum of all these forces acting on a particle is hereinafter referred to as
an adhesive force.
De-Aggregation and Entrainment of Particles
The main objective of the Air-razor is to de-aggregate and entrain the deposited
particles into the air stream. The particles may be loaded onto a substrate member
in many layers in such a way that some particles are in contact with the substrate
member whilst others are in contact only with other particles. A complete de-aggregation
is to separate all the particles from each other. To separate a particle from its
environment involves overcoming the adhesive force as well as the friction force,
acting on the particle.
FIG. 11 illustrates forces acting on a particle. The force caused by airflow
303 acting on a particle 101 can be divided into two parts, drag
force 305 acting parallel to the airflow, and lift force 304 acting
perpendicular to the airflow. The condition for freeing the particle is in the
static case that lift and drag forces exceed adhesion 301 and friction 302 forces.
In order to completely, or almost completely de-aggregate particles it is not
sufficient to let a force act on the particles with enough strength for release
and entrainment. If a strong force acts on an aggregate of particles, such that
more or less the same force acts on all particles, the aggregate will be entrained
into the airflow without de-aggregating. The condition for de-aggregation may thus
be stated as: The difference in external forces acting on two particles must overcome
the adhesion and friction forces holding them together. Attaining a difference
in force from airflow may be done efficiently by creating shear forces, and hence
the Air-razor invention makes use of high shear forces in the area of the powder
deposited for instance onto a substrate member.
Shear Forces
Creating high shear forces implies creating a big velocity gradient in the
flow, which is illustrated by the equation for shear stress in a fluid;
##EQU1##
where
- μ=Dynamic viscosity
- U(y)=Air speed U is a function of y
- y=Distance from wall surface
- dU/dy=Velocity change per unit distance
To develop high shear stress and thereby high shear forces on the particles,
the
main principles used in the Air-razor are:
- High velocity of the air stream
- Use of flow streamlines close to a wall
- Use of turbulent flow (side effect from high velocity)
High Velocity Flow
High velocity flow is the basis for high shear forces (close to a wall), drag
forces, lift forces and turbulence. For a given pressure drop driving airflow,
the objective should be to reach maximum velocity. The theoretical maximum velocity
from a certain static pressure drop can be derived from Bernoulli's streamline
theorem. In reality, there will always be dissipation of energy and the velocity
will not reach the levels stated by the equation, but it can be used as a limit
value.
##EQU2##
where
- p=Static pressure
- ρ=Density of fluid
- u=Velocity
- H=Constant
The equation is called Bernoulli's streamline theorem. H is a constant along
a streamline for an ‘idea’ fluid. Hydrostatic pressure is here excluded
from the equation.
The efficiency of the Air-razor method may be optimised by careful design of
the geometry of involved flow elements with the aim to reach as high a velocity
as possible in the de-aggregation area, but at the same time a smooth transportation
of air in other areas. This will minimise the dissipative losses where not wanted
and so preserve energy for use in the area adjacent to the powder. When suction
is applied to a nozzle, a low-pressure develops that accelerates the air through
the nozzle during a short period before a steady state condition is reached. Initially,
during the start-up period as the air picks up inertia, the velocity is not high
enough to generate the necessary shear forces. Preferably, during this initial
period the Air-razor pauses before the powder onto a substrate member is brought
adjacent to the nozzle. This ensures that the conditions for an efficient de-aggregation
of the powder exist before a point at the border of the powder contour is attacked
by the air stream.
Flow Close to a Wall
A high velocity flow close to a wall will create high shear forces and this is
used in the present invention. The flow at zero distance from a wall is always
zero. This is known as the ‘No slip’ condition and is true for all
fluids. In a thin layer close to the wall the flow velocity will increase rapidly
with the distance from the wall, and the shear stress in this boundary layer will
be correspondingly high. This boundary layer can be laminar or turbulent. The velocity
profile and gradient differ between turbulent and laminar boundary layers, where
the higher gradients and thus shear stress exist in the turbulent layer. The Air-razor
invention makes use of the concentrated flow close to the nozzle inside wall as
well as the wall of the substrate member, and especially the small gap between
the aperture wall on the nozzle inlet and the substrate member.
The area experiencing high shear stress is normally small in relation to the
area occupied by the powder. Therefore, a relative motion between the nozzle and
the powder is introduced. This allows the concentrated small area of high shear
stress to traverse the entire amount of powder for instance onto a substrate member.
Turbulent Flow
FIG. 12 illustrates in form of a diagram typical velocity characteristics for
laminar 311 and turbulent 310 boundary layers. The velocity gradient
and so the shear stress is larger in the turbulent layer. A turbulent flow, either
in a boundary layer or in a free streaming flow, is characterized by irregular
flow with eddies in various sizes and frequencies. Turbulent flow fluctuates in
both time and space. In any particular moment, high gradients of velocity can be
seen and so it is clear that high shear stress exists in the turbulent flow away
from wall surfaces. This means that particle aggregates can be de-aggregated within
a turbulent air stream even after the entrainment into air of an aggregate of particles.
Another advantage of turbulence depends on the fluctuations in the turbulent flow
with time, which will affect the particles with a force varying in time. In fully
developed turbulence, the frequency of the fluctuations will cover a large span,
i.e. from low to high frequencies. Should the frequency of the varying force come
close to a resonance frequency of a particle-particle system or a particle-wall
system, the amplitude will grow bigger and separation may occur even though the
static force is too weak for separation.
The criteria determining whether the flow is turbulent or not are Reynolds number
together with the geometry of the fluid transporting channel. The absolute level
of Reynolds number where transition from laminar to turbulent flow will take place
depends on the surface roughness and said geometry. Keeping these constant, the
value of Reynolds number will determine the nature of the flow. As seen below Reynolds
number is proportional to velocity, hence the velocity has a direct influence on
the turbulence.
##EQU3##
where
- Re=Reynolds number
- U∞=The free stream velocity
- L=Typical length
- v=Kinematical viscosity
Air-Razor Movement
The importance of shear forces for an efficient de-aggregation of particles and
the theoretical background as to why has been discussed in the foregoing. The relative
motion introduced between the nozzle and the load of powder, i.e. the substrate
member normally serving as carrier, is instrumental in attaining and maintaining
the desired conditions stated for de-aggregating all of a powder load and not just
part of it. The main advantages given by the motion are:
- During an initial acceleration phase inertia builds up giving a high
velocity air flow
- Shear forces close to a wall are spread over a large area
- Efficient use of energy
Inertia Build Up
The low-pressure created by the suction through the nozzle drives air to flow
in the direction of the low-pressure. Building up inertia means accelerating the
mass in a system, i.e. the mass of the air itself, hence giving the desired high
velocity air flow after the acceleration period. The velocity of the flow increases
to a point where the flow resistance makes further increase impossible, unless
the level of low-pressure is decreased, i.e. the pressure drop is increased, or
the flow resistance is decreased.
Shear Force Spreading
The area for de-aggregation with high shear forces is concentrated close to the
wall of the nozzle. This concentrated area is small compared to the dose area onto
a substrate member, especially if the dose comprises finely divided powder of high
porosity. The relative motion between the nozzle and the dose will make the small
and concentrated area of high shear stress traverse over the area occupied by the
dose. Depending on the actual spatial distribution of the powder in the extended
dose and the distance perpendicular to the direction of the motion between the
powder and the nozzle inlet aperture, it may occur that the nozzle makes contact
with some of the powder. In such a case the efficiency of the Air-razor method
is not detrimentally affected because of the "hoover" effect. The velocity of the
airflow will not be affected by the motion of the nozzle in relation to the powder
dose, because the speed of the relative motion is very much lower than the velocity
of the air flow going into the nozzle inlet. However, the motion of the nozzle
forcibly shifts the position of the driving low-pressure relative the contour of
the dose in the direction of the motion. Thus, the area of high shear forces moves
along a path, controlled by the relative motion of the nozzle, such that the high
shear forces gradually disperse powder particles into air. Preferably, the path
begins just outside a point of contact between the high shear force area of flowing
air and the border of the powder dose contour and follows the contour outline from
the beginning until the end. Thus, the gradual de-aggregation and dispersal of
a medication powder is an inherent essential characteristic of an Air-razor method.
The area of high shear stress adjacent to a nozzle is illustrated in FIG. 10.
FIG. 10 illustrates graphically the resulting air speed from a suction effort applied
to the nozzle outlet as a function of coordinates in a plane perpendicular to a
substrate member plane through the longitudinal centerline of the same, thus showing
a cross section view of the nozzle 1. The air velocity is illustrated by
a multitude of arrows pointing in the direction of the flow, the length of the
arrows indicating the relative velocity of air at the point in question, thus showing
how the air velocity varies with the position relative the nozzle aperture. The
direction of the relative motion between the nozzle and powder load is indicated
by the arrow "v". Still air 21 is gradually accelerated into an air stream
20 of 60 1/min, steady state, going into the nozzle and controlled by the
suction. The resulting shear forces reach a maximum in the area designated 25.
The illustration in FIG. 10 is an example of an embodiment of a nozzle. The area
of the nozzle aperture may have different form 3 (see FIG. 6) for different
applications, but a circular or elliptic shape is preferred. Likewise, the aperture
wall thickness and curvature 26 may be given different forms depending on
the application, since the form has a great influence on the flow pattern for the
air being sucked into the nozzle.
Efficient Use of Energy
The dosing time interval for de-aggregation and dispersal of powder by an Air-razor
may be selected, depending on the application within a time frame of an inhalation.
Most prior art inhalers will use the inhalation power from the user during a short
period only. This means that the total energy used for de-aggregation is correspondingly
low in these inhalers, unless external de-aggregation energy is supplied. The time
interval for an Air-razor delivery may e.g. be set to 1 second, which means that
the inhalation power during this full second is used for de-aggregating particle
aggregates.
##EQU4##
The total energy E equals the time integral of the power P over the entire period
T, e.g. T=1 second.
Should the selected dosing time interval be too short, full entrainment of
particles will not take place. The effect on a system comprising an Air-razor will
be large-scale retention of powder onto the substrate member. A model is therefore
needed for assessing the number of particles dispersed into air with time. One
such model assumes that a fluctuating turbulent flow is acting on the particles.
Some of the eddies will be strong enough to separate particles in an aggregate
or from a surface. The successful eddies will occur with typical time intervals
based on probability. Each eddy will set a fraction of the total particles free.
If all particles experience the same adhesion force, the model holds true and the
entrainment rate would typically follow an exponential curve. However, the adhesion
force varies from particle to particle and some will stick harder than others will
and the fraction of hard-sticking particles will increase with time. This slows
down the release rate. Hence, a modified model has been suggested, which describes
the rate of particle release as a 1/t-curve, where t represents time and so the
total number of particles n dispersed in the airflow will typically follow its
integral, a loge (t)-curve, illustrated in FIG. 13. The curve
describes the entrainment over a ‘long time’. A significant fraction
of the powder will also be released within a short time (typically 10 ms). The
graph underlines the importance of using a moderate speed v between the nozzle
and the powder envelope. Too high speed will give insufficient time on ‘each
spot’ and thus leave a significant amount of powder undispersed, still onto
the substrate member. Too low speed will jeopardize the objective of delivering
the load of powder within a specified dosing time interval.
The preferred embodiments use substrate members to serve as carriers onto which
medicament powders may be
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