U.S. patent number 3,669,113 [Application Number 04/871,468] was granted by the patent office on 1972-06-13 for inhalation device.
This patent grant is currently assigned to Fisons, Limited. Invention is credited to Roger Edward Collingwood Altounyan, Harry Howell, deceased.
United States Patent |
3,669,113 |
Altounyan , et al. |
June 13, 1972 |
INHALATION DEVICE
Abstract
A method and device for dispensing a particulate medicament
material from a container. The container provided with at least one
powder outlet is rotated by pneumatic means about an axis of the
container. The axis of rotation is caused to precess so as to
describe a path of precession which is contained within a generally
conical surface of precession, and the axis of rotation of the
container is at an angle to the axis of the generally conical
surfaces of precession. This causes the walls of the container to
undergo repeated changes in radial acceleration with respect to the
axis of the generally conical surface of precession, which changes
of acceleration are of sufficient magnitude to overcome the
centrifugal and cohesive forces which hold the particles of powder
in place upon the wall of the container.
Inventors: |
Altounyan; Roger Edward
Collingwood (Wilmslow, EN), Howell, deceased;
Harry (LATE OF Castle Donnington, EN) |
Assignee: |
Fisons, Limited (London,
EN)
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Family
ID: |
27447140 |
Appl.
No.: |
04/871,468 |
Filed: |
June 18, 1969 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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745774 |
Jul 18, 1968 |
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532271 |
Mar 7, 1966 |
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Foreign Application Priority Data
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May 16, 1969 [GB] |
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25,067/69 |
Jan 8, 1969 [GB] |
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1,206/69 |
May 16, 1969 [GB] |
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25,069/69 |
Jun 7, 1968 [GB] |
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27,210/68 |
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Current U.S.
Class: |
128/203.15 |
Current CPC
Class: |
A61M
15/0028 (20130101); A61M 15/00 (20130101); A61M
15/0006 (20140204); A61M 15/0008 (20140204); A61M
15/0033 (20140204); A61M 2202/064 (20130101) |
Current International
Class: |
A61M
15/00 (20060101); A61m 015/00 () |
Field of
Search: |
;128/266,206,208 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Michell; Robert W.
Parent Case Text
This application is a continuation-in-part of our application Ser.
No. 745,774, filed July 18, 1968, which in turn was a
continuation-in-part of our application Ser. No. 532,271, filed
Mar. 7, 1966.
Claims
We claim:
1. A method for dispensing a particulate medicament from a
container, which comprises placing a container provided with at
least one powder outlet on one end of a rotatable member,
supporting the rotatable member only at the other end a bearing
means so shaped as to give to the axis of rotation of said
rotatable member during rotation of the rotatable member a path of
precession which is contained within the generally conical surface
of precession and maintaining the axis of rotation of the container
at an angle to the axis of the generally conical surface of
precession while leaving the said one end of the rotatable member
free, and pneumatically rotating said rotatable member for rotating
the container about an axis of the container for causing the walls
of the container to undergo repeated changes in radial acceleration
with respect to the generally conical surface of precession, which
changes of acceleration are of sufficient magnitude to overcome the
centrifugal and cohesive forces which hold the particles in place
upon the wall of the container.
2. A method as claimed in claim 1 wherein the included angle of the
generally conical surface of precession is from 1/2.degree. to
60.degree..
3. A method as claimed in claim 2 wherein the included angle is
from 1.degree. to 5.degree.
4. A method as claimed in claim 1 wherein the effective motion of a
point on the container wall is a circular sequence of cusps leading
into one another at nodes, and the number of said nodes occurring
per rotation of the container axis about the axis of the generally
conical surface of precession is from 2 to 25.
5. A method as claimed in claim 4 wherein the number of nodes is
from 3 to 10.
6. A device for dispensing a particulate medicament material from a
container, comprising a rotatable member having a free end and said
free end having means to receive the container, two cooperating
bearing means, one bearing means being a shaft and the other being
at least one bearing member within which said shaft is journalled,
one of said bearing means being on the end of said rotatable member
opposite said free end and the other bearing means being fixed,
said shaft and said bearing member providing the sole support for
said rotatable member and being so shaped as to give the axis of
rotation of said rotatable member during rotation of the rotatable
member a path of precession which is contained within a generally
conical surface of precession and maintaining the axis of rotation
of said rotatable member at an angle to the axis of the generally
conical surface of precession, and means associated with said
rotatable member for pneumatically rotating it.
7. A device as claimed in claim 6 further comprising an elongated
tubular housing within which the rotatable member and the shaft and
bearing member are mounted, one of said shaft and bearing member
being rigidly mounted substantially co-axially with the
housing.
8. A device as claimed in claim 6 wherein the shaft and bearing
member are in frictional contact.
9. A device as claimed in claim 6 wherein the rotatable member has
at least one vane thereon for rotating the member upon the passage
of a gas stream through the device.
10. A device as claimed in claim 6 which comprises a rotatable
shaft mounted in a stationary bearing member, the free end of said
shaft carrying a universal joint, a further shaft connected to said
first shaft by means of said universal joint whereby the free end
of said further shaft may be displaced during rotation thereof at
an angle about the axis of said stationary bearing member, the free
end of said further shaft carrying means to receive a container, a
stationary annular bearing member loosely encircling said further
shaft, said annular bearing member and a portion of said further
shaft contacting one another in a frictional contact during
rotation of said further shaft.
11. A device as claimed in claim 10 wherein said further shaft and
said stationary annular bearing member contact one another in a
rolling contact at substantially all times during operation of the
device.
12. A device as claimed in claim 6 in which the bearing member has
an annular bearing surface and the shaft is journalled loosely in
the bearing member, one of said shaft and said bearing being
stationary, the other being on the rotatable member to be rotated
by the pneumatic rotating means, the rotatable member being capable
of being displaced during rotation thereof at an angle about the
axis of the stationary member, the annular bearing surface of the
bearing member and at least a portion of the shaft contacting one
another in frictional contact during rotation of the rotatable
member.
13. A device as claimed in claim 12 wherein the bearing member is a
bearing tube contacting the shaft at both ends of the bearing
tube.
14. A device as claimed in claim 13 wherein the shaft is a rigid
substantially uniformly cylindrical shaft and the bearing tube is
an internally tapered bearing tube.
15. A device as claimed in claim 13 wherein the bearing tube has
annular ridges at at least one end thereof, said ridges providing
an annular bearing surface against which the shaft bears.
16. A device as claimed in claim 13 wherein the diameter of the
shaft and the internal diameter of the bearing tube at the contact
between that end of the bearing tube and the shaft generating the
non-dominant motion number for the non-dominant motion of a point
on the container wall will have a value in excess of 15.
17. A device as claimed in claim 16 wherein the total clearance
between the shaft and bearing tube at that end of the bearing tube
generating the non-dominant motion is minimized at the non-dominant
point of contact.
18. A device as claimed in claim 13 in which a bearing tube is
rotatably mounted on a stationary shaft, and there is a dominant
contact and a non-dominant contact between the shaft and bearing
tube, the dominant contact being a rolling contact, the dimensions
of the bearing tube and shaft being in the relationship.
a/h (R.sup.2 /R-r) > R.sub.c and the term
a/h (R.sup.2 /R-r)
exceeds the term R.sub.c by a sufficient amount of achieve
fluidization of powder within a container mounted in the device,
and wherein a is the distance of the base of the parallel walled
section of the container wall from the non-dominant contact between
the shaft and bearing tube, h is the distance between the dominant
and non-dominant contacts between shaft and bearing tube, R is the
internal radius of the bearing tube at the dominant contact, r is
the radius of the shaft and R.sub.c is the internal radius of the
container at the base of the parallel walled section of the
container wall.
19. A device as claimed in claim 13 in which a shaft is rotatably
journalled in a stationary bearing tube and there is a dominant
contact and a non-dominant contact between the shaft and bearing
tube, the dominant contact being a rolling contact, the dimensions
of the bearing tube and the shaft being in the relationship
a/h (r.sup.2 /R-r) > R.sub.c and the term
a/h (r.sup.2 /R-r) exceeds the term R.sub.c
by a sufficient amount to achieve fluidization of powder within a
container mounted in the device; and wherein a is the distance of
the base of the parallel walled section of the container wall from
the non-dominant contact between the shaft and bearing tube, h is
the distance between the dominant and non-dominant contacts between
the shaft and bearing tube, R is the internal radius of the bearing
tube at the dominant contact, r is the radius of the shaft and
R.sub.c is the internal radius of the container at the base of the
parallel walled section of the container.
20. A device as claimed in claim 12 wherein the shaft is the
stationary member and the bearing member is the rotatable
member.
21. A device as claimed in claim 12 in which the shaft is a rigid
substantially uniform cylindrical shaft and the bearing member is
an internally tapered rotatable bearing tube which has an internal
diameter at that end at which the free end of the shaft is
positioned which is smaller than the internal diameter at its outer
end.
22. A device as claimed in claim 21 wherein the bearing tube has an
internal diameter at the inner end which is from 1.5 to 6.0 percent
greater than the diameter of the shaft and an internal diameter at
the outer end which is equal to the diameter of the shaft plus from
1.3 to 3.5 percent of the internal length of the bearing tube.
23. A device as claimed in claim 22 wherein the bearing tube has an
internal length of from 4 to 10 times the diameter of the
shaft.
24. A device as claimed in claim 11 wherein the shaft and bearing
member contact one another in a rolling contact at substantially
all times during operation of the device.
25. A device as claimed in claim 6 further comprising a powder
capsule mounted upon the rotatable member.
Description
The present invention relates to a method whereby particulate
medicament materials may be dispersed from a container using a
fluidization technique. The invention also provides devices for use
in the method of the invention.
Accordingly, the present invention provides a method for dispensing
a particulate medicament material from a container which comprises
rotating a container provided with at least one powder outlet by
pneumatic means about an axis thereof and causing the axis of
rotation to precess so as to describe a path of precession which is
contained within a generally conical surface of precession. By
generally conical is meant a surface of precession which is a cone
or frusto-cone of precession. The axis of rotation of the container
being at an angle to the axis of the cone or frusto-cone of
precession. By the expression "at an angle to" is meant an axis of
rotation which intersects the axis of the cone or frusto-cone of
precession as well as an axis of rotation which does not intersect
said axis of the cone or frusto-cone of precession. The walls of
the container undergo repeated changes in radial acceleration with
respect to the axis of the cone or frusto-cone of precession, which
changes of acceleration are of sufficient magnitude to overcome the
centrifugal and cohesive forces which hold the particles in place
upon the wall of the container.
We believe that during the motion generated by the method of the
invention any point on the wall of the container executes a motion
of a trochoidal nature in the radial plane of the cone or
frusto-cone of precession. The trochoidal motion may be
epitrochoidal or hypotrochoidal. As the container rotates,
particulate material is centrifuged against the container wall and
is held in place thereby frictional and cohesive forces. During the
trochoidal motion the particles are subjected to several changes in
radial acceleration of the wall of the container. If the
acceleration of the wall of the container away from the axis of the
cone or frusto-cone of precession is sufficiently great, the forces
holding the particles in place upon the wall are overcome. The
particles then leave the wall and adopt free flight within the
container whose walls continue to move along the trochoidal curve.
The particles later impinge upon the container wall at a different
point to that at which their free flight was initiated. It is
believed that, since the container's axis of rotation is inclined
to the axis of the cone or frusto-cone of precession, the particles
impinge upon the container wall at a point displaced along the axis
of the container. The particles thus undergo fluidization within
the container and also axial feed along the container.
The occurrence of fluidization and the rate and extent of movement
of particles within the container are dependent upon a number of
inter-related factors, such as the relative diameters of the
container and the cone or frusto-cone of precession at the base of
the container, the speed of rotation of the container, the relative
angular speeds of rotation of the container and its precession, the
size of the included angle of the cone or frusto-cone of
precession, the nature of the particulate material within the
container and its interaction with the material of the container
wall.
The motion generated by the method of the invention consists in
essence of a circular sequence of cusps leading into one another at
nodes, which may be transition curves, simple points or small loops
linking one cusp to the next. The magnitude of the variations in
radial acceleration undergone by a point on the container wall
depends upon the number of cusps which occur during each revolution
of the container about the axis of precession and upon the
difference between the apogee and perigee of the locus of the point
on the container wall as it moves around the axis of precession.
These variables are themselves functions of the factors referred to
above and may be varied over a wide range according to the form and
size of the device used to generate the required motion. However,
the energy available to fluidize powder on the container wall
during the traversal of each cusp is inversely proportional to the
number of nodes occurring per rotation of the container axis about
the axis of precession, or the nodal number as this ratio will be
termed hereinafter. At excessively high or low nodal numbers
fluidization within the container may be inadequate and we prefer
that the nodal number should be from 2 to 25, preferably 3 to 10,
to achieve satisfactory fluidization. The nodal number need not be
an integer. As will be shown later, the nodal number is a function
of the dimensions of the device generating the motion. Having
established suitable dimensions for a device so as to achieve the
desired nodal number, the difference between the apogee and perigee
of the locus of a given point on the wall of the container may be
varied to secure fluidization. This variation may be achieved by
altering the size of the included angle of the cone or frusto-cone
of precession and/or by altering the radius of the container and/or
by altering the distance of the container from the apex or notional
apex of the cone or frusto-cone of precession, which effectively
alters the diameter of the cone or frusto-cone of precession at the
container. A decrease in the container radius or an increase in the
distance between the container and the apex of the cone or
frusto-cone promotes fluidization. It will of course be appreciated
that these factors are inter-related with the nodal number and that
fluidization may be achieved by many permutations of these factors.
However, if the included angle of the cone or frusto-cone of
precession is high, say 60.degree. or more, then the rate of axial
feed of particles within the container is extremely rapid. Whilst
movement of particles along the axis of the container will occur at
very small cone angles, e.g. less than about 0.5.degree., such
movement will be relatively slow. An included angle of about
1.degree. to 5.degree., preferably about 2.degree., will usually
give an adequate rate of movement, provided that adequate
fluidization occurs.
The other factors referred to above are not readily susceptible to
such generalized statements in view of their close
inter-relationship and their dependence upon the size and nature of
the device generating the motion and its intended use.
The motion required by the method of the invention may be generated
by a number of forms of device. For example, the container may be
mounted upon a rigid shaft having a universal joint therein. The
free end of the shaft is rotatably mounted by means of a
conventional lubricated bearing assembly, such as a ball or roller
race or a bush type bearing. Between the container and the
universal joint is a bearing adapted to retain the angle of the
cone of precession of the shaft within the desired range. This may
take the form of an annular ring surrounding the shaft and which
engages with a bearing shoulder on the shaft (this type of device
generates hypotrochoidal motion), or may take the form of an
annular shoulder on the shaft which shoulder is provided with a
dependent annular bearing skirt whose inside surface engages with
the outside bearing surface of a fixed annular ring of smaller
diameter (this type of device generates epitochoidal motion). In an
alternative form, the universal joint may be replaced by a flexible
shaft. Furthermore, by introducing assymetric flexibility into the
shaft, for example by making it with a polygonal cross-section e.g.
a triangular, square or hexagonal section, it may not be necessary
to provide the restraining bearing.
The motion may also be generated by a rigid shaft carrying the
powder container rotating within two spaced annular bearing rings
of different diameters. The annular bearing rings may take the form
of a tapered bearing tube where contact between the shaft and
bearing occurs at the top and bottom extremes of the tube, and the
term bearing ring is used herein to denote not only an annular
bearing surfaced member, but also an annular area of contact
between a shaft and a bearing surface. Such a bearing tube may be
provided with a ridge or an inserted protruding lip at its top
and/or bottom extremes to provide the contacting bearing rings or
may be concaved between its ends to achieve the same effect.
Alternatively the bearing rings may be of the same diameter and the
shaft be tapered. It will also be appreciated that the shaft may be
the stationary member and that the powder container may be carried
by the tapered bearing tube. The difference in diameter between the
shaft and the bearing rings affect the nature of the motion
generated.
During the motion generated by the above devices, each contact
between the shaft and a bearing ring will generate a motion wherein
the ratio of the frequency of rotation of the container about the
axis of the cone or frusto-cone of precession to the frequency of
rotation of the container about its own axis (or the frequency
ratio as this ratio will be termed herein) is dependent on the
ratio of the diameter of the moving member to the difference in
diameters of the moving and stationary members. The greater the
difference in diameters between the moving and stationary members,
the more eccentric and in general more dominant will be the
trochoidal motion generated by that contact. Where the moving
member rotates within the stationary member, the nodal number is
one more than the frequency ration, whereas where the moving member
rotates around the outside of the stationary member, the nodal
number is one less than the frequency ratio. Each bearing ring, or
its equivalent, generates its own trochoidal motion and, where
there are two bearing rings, these motions combine to yield an
overall resultant motion for the free end of the shaft.
It is desirable that the effect of the non-dominant motion should
either be minimized or should complement the motion generated by
the dominant bearing ring. Whilst the latter may be achieved by
ensuring that the nodal number of the non-dominant motion is an
integer multiple of, e.g. 2, 3 or 4 times, the nodal number of the
dominant motion, such an exact relationship may prove difficult to
achieve in practice. We therefore prefer to minimize the effect of
the non-dominant motion. Usually the non-dominant motion is
generated by the smaller bearing ring and the effect of the motion
of this ring may be minimized by decreasing the total clearance
between the shaft and this bearing ring. This increases the nodal
number of the motion generated and we have found that in general,
if the nodal number at a point on the container wall of the
non-dominant motion is in excess of 15, preferably in excess of 30,
the effect of this motion is reduced to a satisfactory extent.
It will be appreciated that the distance between the bearing rings
and the clearances between the shaft and the bearing rings will
determine the included angle of the cone or frusto-cone of
precession.
A particularly preferred form of bearing ring and shaft for
generating the motion required by the method of the invention is
one wherein a rigid substantially uniform cylindrical shaft is
journalled in an internally tapered bearing tube, notably one
wherein the bearing tube has an internal diameter at its inner end
(i.e. that end housing the free end of the shaft) which is smaller
than the internal diameter at its outer end. It is especially
preferred that the shaft be the stationary member and that the
bearing tube be rotatably mounted on the shaft. With such a device,
fluidization within a container mounted on the bearing tube will
occur when the changes in radial acceleration undergone by the
container wall due to the motion generated by the dominant contact
between the shaft and bearing are sufficiently large to overcome
not only any conflicting acceleration generated by the non-dominant
contact and the cohesive forces amongst the particles and between
the particles and the container wall, but also overcome the
centrifugal forces generated during the motion. In an ideal case
the effects of the non-dominant motion would be nil and, if one
ignores inter-particle forces, we have found that fluidization in
such an ideal case will occur at a given point on the container
wall when the tapered bearing tube is rotated in rolling contact
upon the stationary shaft if the expression:
a/h (R/R-r) > R.sub.c
is satisfied, a is the distance of the base of the parallel walled
section of the container from the non-dominant contact between the
shaft and bearing, h is the distance between the dominant and
non-dominant contacts between shaft and bearing, R is the internal
radius of the bearing at the dominant contact, r is the radius of
the shaft and R.sub.c is the internal radius of the container at a
distance a from the non-dominant contact between the shaft and
bearing. Usually the limiting case for fluidization will be at the
base of the powder container where this has a flat bottom and
parallel side walls. However, where the container has a rounded
bottom, the limiting case may be at some point above the base, for
example at the start of the parallel walled portion thereof. The
limiting case may be readily ascertained.
It must be emphasized that the above expression represents the
minimum requirements for fluidization under the conditions
specified. However, inter-particle forces must also be overcome and
the non-dominant motion may conflict with the dominant motion to
reduce the fluidizing forces generated. The left hand side of the
above expression must therefore in practice exceed the right hand
side by an amount which will vary according to the above factors.
In practice, therefore, the approximate dimensions for a device
established from the above expression may require optimisation by
experimentation. It will be appreciated that a satisfactory device
for present use may be constructed using a wide range of dimensions
in a number of permutations. However, various of the dimensions of
this preferred form of device for present use may be limited by
certain factors, thus reducing the number of possible permutations
which may be made. For example, the energy available in the driving
gas stream will impose limitations on the possible size of the
device as may the strength of the materials used to construct the
device; and, where the device is to be carried in the pocket of a
user, it clearly cannot exceed, say, 6 inches in total length.
Furthermore, the powder container to be used in the device may be
of a standard specified form and size since medicaments are usually
put up in standard gelatin capsules holding, say, 20 - 100 mgs of
drug. For efficient operation the capsule is filled with powder
only to one-half to one-third of its total capacity.
In the form of device where a shaft is journalled in a tapered
bearing tube, it is preferred that the non-dominant contact between
the shaft and bearing generate a motion at the container wall
having a nodal number in excess of 15, preferably in excess of 30,
and that the dominant contact generate a motion at the container
wall having a nodal number of from 2 to 25, e.g. 3 to 10 notably 5
to 7. A suitable motion may, for example, be generated by rolling
contact between a cylindrical shaft and a tapered bearing tube
which has an internal diameter at one end which is from 1.5 to 6
percent, preferably 2.5 to 9 percent, notably about 3.5 percent,
greater than the diameter of the shaft and an internal diameter at
its outer end which is equal to the diameter of the shaft plus from
1.3 to 3.5 percent, notably about 2.5 percent, of the internal
length of the bearing tube. In general it is desirable to use as
fine a rigid shaft as possible, for example a drawn wire shaft of
about 0.080 inches diameter may be used in devices powered by human
inhalation. Typically, the bearing tube may have an internal length
which is 4 to 10, preferably about 7, times the diameter of the
shaft.
It is also preferred that the shaft have a rounded free end which
bears against the flat closed end of the bearing tube. The free end
of the shaft may be of frusto-conical shape, preferably terminating
in an hemispherical tip, which tip has a diameter approximately
half that of the shaft.
The expression a/h (R.sup.2 /R-r)>R.sub.c quoted above is in
relation to a device where a tapered bearing tube is rotatably
mounted upon a rigid cylindrical shaft. However, where the bearing
tube is stationary and it is the shaft which rotates in rolling
contact with the bearing, fluidization of powder within a container
mounted on the shaft will occur under the idealized conditions when
a/h (r.sup.2 /R-r) > R.sub.c ; a, h, r, R and R.sub.c having the
same values as quoted earlier.
In a further form of device, the use of an integral restraining
bearing surface and of a shaft journalled in a bearing tube are
combined by providing the container carrier with a short tapered
shaft which is mounted centrally within a dependent cylindrical
sleeve having an internal dry friction bearing surface. The short
shaft is journalled in a tapered recess in the end of a rigidly
mounted cylindrical boss or shaft. The dimensions of the recess and
of the short shaft are such that the dry friction bearing surface
on the dependent skirt can bear against the exterior of the rigidly
mounted boss or shaft to provide the drive whereby the freely
rotating short shaft is caused to precess.
In the forms of the shaft and bearing configuration described
above, the contact between the shaft and that bearing ring
generating the dominant motion must be frictional in order that
precession may take place. It is preferred that the contact be
rolling and, in order to ensure uniform motion of the container
walls, that this rolling contact be maintained at substantially all
times during the motion. Where two bearing rings are used to
generate the motion, the contact between the shaft and the
non-dominant bearing ring need not be frictional and in some cases
it may be feasible to lubricate this bearing ring, but not the
other, in order to minimize any motion generated by this bearing
ring.
In the mechanisms described above, precession has been achieved by
the fact that the axis of the rotating member upon which the
container is mounted sweeps out a conical or as near conical
surface as can be achieved in practice; that the rotating member or
an integral part thereof bears against a stationary member; and
that the contact between the rotating and the stationary members is
frictional, preferably a rolling contact.
Accordingly, from a further aspect the invention provides an
apparatus for use in the method of the invention which comprises a
bearing member having an annular bearing surface and a shaft
journalled loosely in the bearing member, one of said bearing and
said shaft being stationary, the other being adapted to be rotated
by pneumatic means and to receive a container, the rotatable member
being capable of being displaced during rotation thereof at an
angle about the axis of the stationary member, the annular bearing
surface of the bearing member and the shaft or an integral part
thereof being adapted to contact one another in a frictional
contact during rotation of the rotatable member. In many cases the
design of the stationary and rotatable member will be such that the
rotatable member inherently adopts at all times a position where
its axis is displaced at an angle to the axis of the stationary
member, e.g. as is the case where a stationary shaft carries a
loose fitting bearing tube which even at rest will tend to adopt a
canted position vis a vis the shaft. However, in some cases, the
rotatable member may adopt a substantially coaxial position with
respect to the stationary member when at rest, as is the case with
a flexible shaft surrounded by a restraining bearing ring as
described above, yet during rotation may be deflected or whip so
that the rotating member and the stationary bearing surface may
come into contact to generate the desired precession.
Other mechanisms may readily be devised, such as epicyclic gear
systems and the like, which will cause the container to rotate and
precess in the manner required. Thus, a further form of mechanism
is a shaft freely journalled in a bearing, the requisite wobble in
the rotation of the shaft being achieved by means of the repeated
attraction and repulsion of magnets mounted in the housing or shaft
and the bearing. Alternatively, the precession of the container
axis within a cone or frusto-cone of precession may be achieved by
mounting the container at an angle in a cup provided with a vane or
vanes, which cup is rotatably mounted off center on a boss provided
with a vane or vanes, which boss is itself rotatably mounted. The
passage of air past such an arrangement would cause rotation of
both the boss and the cup causing the axis of the container to
rotate and precess in the desired manner. In these two forms of
device the shaft and bearing assemblies should not be in rolling
contact, i.e. are in sliding contact, and may be lubricated to
assist their relative rotation.
The invention thus also provides an apparatus for use in the method
of the invention which comprises a rotatable member carrying means
to receive a container, which rotatable member is mounted by means
of a shaft journalled within at least one bearing member and is
adapted to be rotated pneumatically and to process so that its axis
of rotation describes a path contained within a cone or frusto-cone
of precession, the axis of rotation of the rotatable member being
at an angle to, but not necessarily intersecting, the axis of the
cone or frusto-cone of precession.
As has been stated above, the rotatable member which is to carry
the container is to be rotated pneumatically, for example by a gas
stream generated with a rubber squeeze bulb or merely by the
inhalation of air by a human user. The pneumatically driven means
may take any of the conventional forms, such as a propeller or
turbine assembly. Such pneumatically driven means will for
convenience be denoted hereinafter by the general term vanes,
although this term is intended to include not only a plurality of
vanes as with a turbine, but also a single vane as with an
Archimedian screw. The vanes may be mounted integrally with the
shaft or bearing tube carrying the container, the container
receiving means, the container itself, or where the shaft is
jointed, as is the case where it has a universal joint, the vanes
may be mounted above or below the joint. It is usually preferred to
have the vanes mounted integrally with the container receiving
means in the form of, say, a propeller and boss on the end of the
shaft, or bearing tube, the boss being provided with means for
receiving a container.
Usually the gas stream driving the device will flow past the powder
container. However, it may be desirable to prevent an excessive
flow of driving gas past the container. It is therefore within the
scope of the present invention to provide means for isolating the
container from the driving gas stream. This may be done for example
by providing a shroud, e.g. a sleeve, around the container which
effectively channels the gas stream away from the container.
Alternatively where the container is mounted on a universally
jointed shaft, that portion of the shaft which is supported in the
bearing means may be journalled in a chamber separated from that
part of the shaft carrying the container and the gas stream only
through that chamber.
The powder container for present use may be of any shape or size
suited to the intended rate of dispensing and total weight of drug
to be dispensed. However, it is preferred that the powder container
be a capsule or cartridge, e.g. an hard gelatine capsule, notably
one of the gelatine capsules which are of the accepted standard
sizes for drug use, e.g. of 20 to 100 mg capacity. Typical of such
capsules are those gelatine capsules of internal diameter about 6.3
mms. In order that the medicament powder within the container may
be dispensed into the airstream flowing past the container, the
container is provided with one or more outlets for the powder.
Conveniently, these take the form of perforations in the wall of
the container, which holes are preferably symmetrically arranged
around the wall. With a gelatin capsule it is preferred that the
holes be in a shoulder of the capsule and that they be of from
about 0.6 mms to about 0.65 mms in diameter. It will be appreciated
that the container should be mounted in any device with the holes
in the free end of the container.
The rotating member in devices for present use is provided with
means for mounting a powder container thereon. This means is
preferably such that the powder container is mounted co-axially
with the axis about which the rotating member rotates and is held
rigidly in place during operation of the device. This may be
achieved by forming a recess in the end of the rotating member
which recess is of similar configuration to the powder container
and receives the container in a push tight fit. Thus where the
rotating member is provided with a terminal boss carrying propeller
blades, the boss may be cut with a cup shaped recess to receive a
medicament capsule in a push tight fit.
The stationary and rotating members used to generate the motion
required by the invention will usually be mounted in an housing
adapted to lead the driving gas stream through the vanes by which
the rotatable member is to be rotated. This gas stream will also
usually flow past the powder container and the housing may
therefore take the form of an elongated tube within which the
rotating and stationary member are mounted. The stationary member
is preferably mounted substantially co-axially with the tubular
housing and should be rigidly mounted since undue flexing thereof
may cause malfunctioning of the device. The housing may also be
provided with other features which may be required for optimum
operation of the device. Thus, where the powder container is to
dispense powder continuously, means may be provided for supplying
powder to the container; means may be provided for generating the
driving gas stream, e.g. a rubber squeeze bulb; or the housing may
be provided with a non-return valve which permits the passage of
gas through the device in only one direction. As indicated below,
the method of the invention is of especial use in dispensing
powdered medicament into an air stream which is being inhaled.
Particularly preferred devices for present use are therefore of a
suitable size for convenient use, and are provided with a tubular
housing for the stationary and rotating members which housing is
provided with a mouthpiece via which the user can inhale air
through the device. The rotating and stationary members are
preferably mounted within such an housing so that the vanes which
are to rotate the rotatable member lie between the intended
position of the powder container and the mouthpiece. It is also
preferred to provide the housing in devices which are to be driven
by the inhalation of air therethrough by a user with a constriction
or venturi section in order to increase the air flow rate past the
powder container. It will usually be preferred to form the housing
in two parts, one having the mouthpiece and the stationary and
rotating members and the other having the venturi section and the
air inlet. By this means the air inlet may be removed to provide
free access to the mounting for the powder container during loading
or unloading of the container. If desired, the housing may also be
provided with means for piercing the powder container in situ
within the device. It may also be desired to provide means, such as
a shroud, by which powder issuing from the container may be
prevented from depositing upon the contacting surfaces of the
stationary and moving members.
The devices for use in the method of the invention may be made from
any suitable material such as metal, e.g. steel or aluminum, or a
thermoset or thermoplastic synthetic resin, such as polystyrene,
nylon, polyethylene, unreaformaldehyde resins and the like. The
material used will depend upon the sacle on which the dispensing of
powder is to be carried out and the magnitude of the forces
generated. The bearing surfaces may also be made from conventional
materials. However, where precession is achieved by means of a
frictional contact, for example between a shaft and the bush within
which it is mounted, such contacting surfaces should not be self
lubricating and preferably are made from high friction
materials.
The method of the invention finds widespread use wherever it is
desired to dispense medicament powders into an airstream. Thus, it
may be used to dispense antibiotic and like powders in a cloud for
deposition on a wound or skin infection. However, as indicated
above, the method finds especial use in the dispensing of
medicament into an airstream which is to be inhaled. The method
affords a means by which very fine particles may be administered
deep into the lungs of a user and, where the device used is one
powered by the user's inhalation, delivers the powder in an amount
proportional to the rate of inhalation and the total volume of air
inhaled, thus automatically regulating the release of medicament
according to the depth of inhalation.
The method may be used to dispense a wide variety of powdered
medicaments and the particles thereof may be of any shape and may
be amorphous or crystalline in nature. However, the method of the
invention is of especial application in dispensing micronized
powders notably those of particle size less than 80 microns many of
which have poor flow characteristics and may not be readily
dispensed by other methods.
The method of the invention will be described by way of example in
relation to various forms of device which may be used to administer
powdered medicament by oral inhalation and with reference to the
accompanying drawings in which:
FIG. 1 is a longitudinal section through a simple form of
device;
FIG. 2 is a longitudinal section through a preferred form of
device;
FIG. 3 is a longitudinal section through a cap suitable for use
with the device of FIG. 2;
FIG. 4 is a longitudinal section through an alternative form of the
device of FIG. 2 wherein the shaft and bearing tube have been
transposed;
FIG. 5 represents an alternative form of bearing tube for use in
the devices of FIGS. 2 and 4;
FIG. 6 is a longitudinal section through an alternative form of a
simple device for generating the motion required by the method of
the invention;
FIG. 7 is a longitudinal section through an alternative form of the
device of FIG. 6;
FIG. 8 is a diagrammatic longitudinal section through a further
alternative form of the device of FIG. 6; and
FIGS. 9 and 10 are diagrammatic longitudinal sections through two
further forms of bearing and shaft assembly which may be used to
generate the motion of the invention.
Referring now to FIG. 1, an inhalation device comprises a tubular
housing 1, one end of which, B, is adapted to be inserted in the
mouth. Mounted co-axially with housing 1 is a shaft 2 having
loosely and rotatably mounted thereon a tapered bearing tube 5
carrying a propeller-like member 3 having blades 4. The
propeller-like member 3 has a cup-like receptacle therein adapted
to engage and hold a perforated capsule 6 containing finely divided
medicament.
When end B of housing 1 is inserted in the mouth and air is inhaled
through the mouth, the resulting airstream causes the
propeller-like member 3 to rotate and precess about shaft 2 with
the result that the finely powdered medicament is fluidized in
capsule 6, is dispensed therefrom and passes with the airstream
past blades 4 out of end B of housing 1 and into the mouth and
respiratory tract of the user.
Referring now to FIG. 2, this form of inhalation device comprises
an housing of approximately circular cross-section having a
diameter of about 1.9 cm. and length of about 5 cm. and comprising
two engaging members 7 and 8, housing member 8 being adapted for
insertion into the mouth and having passageways 9 therein to permit
the passage of air. Mounted rigidly in and co-axially with housing
member 8 is shaft 2 upon which is loosely and rotatably mounted
tapered bearing tube 5 carrying propeller-like member 3 having
blades 4. Propeller-like member 3 has a cup shaped receptacle
adapted to receive and hold a capsule or container of finely
powdered medicament 6 which is pierced with holes in the shoulder
of the free end thereof. The tip 10 of shaft 2 is conical in shape,
having a cone angle of about 30.degree., and terminates in a
substantially hemispherical portion having a diameter of about half
the diameter of shaft 2.
Housing member 7 has in its end wall air passages 11 to permit the
passage of air and constricting member 12 which serves to constrict
the air stream through the device and thus increase its velocity
past the capsule.
Through the end wall of housing member 7 extends locking member 13
which is attached at its outer end to base piece 14. Between base
piece 14 and housing member 7 is a spring 15 which urges locking
member 13 into a normally open position. Base piece 14 has a screw
thread 16 which engages in a similar screw thread 18 in cap 17
(shown in FIG. 3) to hold locking member 14 in a closed position
and to engage and hold capsule 6 mounted in the cup shaped member
of propeller 3. When cap 17 is in position no air may be inhaled
through the device and capsule 6 is firmly held in position. When
cap 17 is removed from the device, spring 15 urges locking member
13 into its open position and air may be inhaled through the device
with consequent rotation of propeller-like member 3 and dispersal
of the finely powdered medicament from capsule 6.
Around locking member 13 is disc 19 which serves as a non-return
valve for the device. Thus, if air is blown through the device disc
19 is urged against the end wall of housing 7 and closes air inlets
11 and thus prevents any further air from passing in that
direction. If air is sucked through the device, disc 19 is urged
away from the end wall of housing 7, freeing inlets 11 and thus
allowing air to pass through the device.
The whole device may be constructed of any suitable materials,
preferably of a synthetic thermoplastic resin such as nylon in
which case it may be made by an injection moulding technique. In
order that the shaft 2 and bearing tube 5 should be in rolling
contact it is preferred to form tube 5 from an hard nylon and the
shaft 2 from drawn wire.
As has been indicated above, the dimensions of the shaft and
bearing affect the precise form of motion generated by the above
device and that satisfactory operation may be achieved by many
permutations of the dimension. It is preferred to ensure that the
clearance between the shaft and the narrow end of the bearing is
less than about five thousandths of an inch in order to minimize
the effects which this clearance will have on the dominant motion
generated by the clearance at the broad end of the bearing. Whilst
it is generally preferred to use as thin a shaft as possible, a
lower limit may be placed on the diameter of the shaft by rigidity
considerations. In the present instance, the use of a drawn
stainless steel shaft of uniform diameter of 0.080 inches and an
hard nylon bearing with a top total clearance of 0.002 inches and a
bottom total clearance of 0.016 inches between the shaft and the
bearing wall is found to give a satisfactory form of motion. The
bearing has a length of about 0.5 inches which gives an included
angle for the frusto-cone of precession of approximately
2.degree..
The forces acting on particles within the rotating capsule will
vary with the diameter of the cone or frusto-cone of precession
which itself varies along the length of the capsule. With the
dimension given above, we have found that, for a capsule about 0.25
inches in diameter, satisfactory fluidization is achieved
throughout the length of the capsule if the capsule is mounted with
the base of its parallel walled portion about 0.2 inches from the
top end of the bearing.
It is emphasized that the specific dimensions given above represent
but one of the many possible permutations that may be made to
obtain a device with essentially similar performance
characterization.
In the device shown in FIG. 4 the shaft and bearing of the device
of FIG. 2 have been transposed. The bearing tube 5a is mounted
co-axially with the housing and shaft 2a is mounted on the lower
end of the propellerlike device 3. Apart from this change, the
construction and methods of use of the devices are similar.
However, it is interesting to note that the transposed device
generates an hypotrochoidal motion whereas the non-transposed
version generates an epitrochoidal motion.
The cosistently effective administration of a powdered material by
the device of FIG. 2 has been confirmed by experimental trials
carried out using a bronchodilator as medicament in which the
device was used to administer over 1,000 doses of bronchodilator to
some 30 persons and the response determined spirometrically.
Inadequate response in any single case was found to be due to lack
of response to the medicament itself, as confirmed by
administration by alternative routes. In all other cases the
administration was found to be fully effective.
In the devices of FIGS. 1, 2, 3 and 4, the fact that there has been
clearance at each end of the bearing has enabled the shaft to lie
across the bearing (rather than have to roll upon one wall of the
bearing). The shaft has therefore contacted the bearing tube at the
widest and narrowest parts only. FIG. 5 shows a further alternative
form of bearing where lack of contact between the extremities of
the bearing tube 5 is achieved by means of a lip 20 in the widest
end of the bearing tube. This lip may be detachable e.g. by virtue
of the fact that it is a snap fit into a co-operating recess in the
bearing tube 5, or may be moulded integrally with the tube 5. The
lip 20 may be made from the same material as the tube 5 or may be
made from a friction pad material to assist rolling contact between
the lip 20 and the shaft 2. In this latter case the tube may be
made from a low friction material, such as polyfluorinated
hydrocarbon resin, e.g. that sold under the Registered Trade Mark
Teflon, in order to minimize the motion generated by the other end
of the bearing tube.
FIG. 6 shows an alternative form of device which generates the
motion of the method of the invention. This device comprises an
elongated tubular housing in two snap fit parts 24 and 25. Mounted
in part 25 by means of struts 26 is a ball race through which an
air stream may pass by means of passages therethrough. In the ball
race is journalled shaft 27 substantially co-axial with the
housing. Shaft 27 is joined by a universal joint 28 to a shaft 29.
Shaft 29 carries on its free end a boss 30 having a cup-like
receptacle adapted to receive a powder capsule in a firm push fit.
Between boss 30 and the universal joint 28, the shaft 29 is
provided with an annular shoulder 31 having a rounded bearing face
32. The housing part 25 has mounted therein by struts 33 an annular
bearing ring 34 around the inside surface of which bearing face 32
may run. There is sufficient clearance between the inside of ring
34 and shoulder 31 to permit the shaft 29 to be displaced through
an extreme angle which corresponds with the desired included angle
for the cone of precession. In order that slip between the face 32
and ring 34 should not occur to an appreciable extent, the ring 34
is made from a hard nylon and the shoulder 32 from hardened
steel.
The vanes necessary to drive the shaft 29 may be mounted either
upon the boss 30 as shown or upon either of shafts 27 and 29.
Part 24 of the housing may be provided with a construction 35.
An alternative form of the restraining bearing for the device of
FIG. 6 is shown in FIG. 7. In this the annular shoulder 31 on shaft
29 is of greater diameter than ring 34 and is provided with a
dependent skirt 36 whose inner face bears against the outer face of
ring 34. It is interesting to note that this form of bearing
produces an epitrochoidal motion, whereas the device of FIG. 6
gives an hypotrochoidal motion.
The device of FIG. 8 is essentially identical to that shown in FIG.
6 except that the pair of shafts 27 and 29 joined by the universal
joint 28 are replaced by a single flexible shaft 37 of circular
cross section which whips during rotation and thus permits the free
end of the shaft 37 to rotate at an angle to the end of the shaft
mounted in the ball race. As the speed of rotation of the shaft 37
increases the free end deflects further until the bearing face 32
of the shoulder 31 on the shaft 37 engages with annular bearing
ring 34 and causes the rotating shaft to precess at the desired
rate. As indicated earlier, the shaft 37 may have a polygonal cross
section, e.g. an hexagonal section. In such an instance the annular
bearing ring 34 and the shoulder 31 may be dispensed with.
FIG. 9 shows a form of shaft and bearing wherein the concept of a
tapered bearing tube is combined with the use of a restraining
bearing ring.
This device comprises an elongated tubular housing 38 within which
is mounted a short rigid cylindrical shaft 39 by means of struts
40. The free end of shaft 39 is indented with a conical recess 41.
A rotatable boss 42 is mounted co-axially upon a short rigid
cylindrical shaft 43 which is loosely journalled in the conical
recess 41 in the end of shaft 39. The boss 42 is also provided with
a dependent annular skirt 44 surrounding the shaft 43, which skirt
has an internal diameter greater than the external diameter of
shaft 39 and is of sufficient length that its internal surface may
engage with the exterior of shaft 39.
Boss 42 is provided with vanes 45, which are adapted to cause
rotation of the boss upon the passage of air through the device,
and with a cup-like recess 46 adapted to receive a powder capsule
in a push tight fit.
The housing 38 may be provided with an internal restriction 47 in
order to increase the air flow rate past a capsule mounted in
recess 46.
When air is passed through the device, boss 42 is caused to rotate,
and in view of the loose mounting of the short shaft 43 in the
recess 41, the inner face of skirt 44 is caused to bear against
shaft 39. The contact between shaft 39 and skirt 44 causes the boss
to precess around its axis of precession. Whilst this contact must
be frictional, and preferably is a rolling contact, the contact
between shaft 43 and recess 41 may be lubricated in order to assist
free rotation of the shaft 43.
FIG. 10 shows a device wherein precession of the axis of rotation
of the container is achieved other than by rolling contact between
a rotating and a stationary member. Such a device comprises an
elongated tubular housing 48 within the housing in a bearing bush
49 of cylindrical bore mounted by struts 50 substantially
co-axially with the housing 48. Within bush 49 is mounted rotatable
cylindrical shaft 51, which may be lubricated to assist its free
rotation in the bush. The free end of shaft 51 carries a boss 52
provided with vanes 53. Off center on boss 52 is mounted a rigid
cylindrical shaft 54 which carries a bearing tube 55 of cylindrical
bore which may be lubricated to assist its free rotation upon shaft
54. The tube 55 carries a boss 56 provided with vanes 57 and with a
receptacle 58, e.g. a cup shaped recess, adapted to receive a
powder container in a push tight fit. The receptacle 58 is so
orientated that a powder container is mounted upon boss 56 at an
angle to the axis of tube 55.
If desired the housing 48 may be provided with a venturi 59 or any
of the other further features provided in the device of FIG. 2 in
order to optimize its operation.
The passage of air through the device causes boss 52 to be rotated,
thus causing shaft 54 to precess about the axis of shaft 51; and
causes boss 56 to rotate which means that a container mounted
thereon is caused to rotate about an axis which is inclined to
shaft 54 and is precessing by virtue of the rotation of boss
52.
It will be appreciated that the device of FIG. 10 may be modified
by mounting shaft 54 with its axis intersecting the axis of shaft
51, i.e. at an angle thereto. The receptacle 58 in the boss 56 may
then be orientated so that a powder container is mounted therein
co-axially with tube 55 rather than at an angle thereto.
In both the above forms of the device of FIG. 10, each shaft and
bearing may be lubricated in order to assist the rotation
thereof.
* * * * *