Note: Descriptions are shown in the official language in which they were submitted.
CA 02542640 2000-07-21
UNIT DOSE CAPSULES AND DRY POWDER INHALER
FIELD OF T$E INVENTION
The present invention is in the field of inhalers.
BACKGROUND OF THE INVEN77ON
In the early 1970's it was found that certain medicines could
be administered in dry-powder form directly to the lungs by inhalation
through the motYth or inspiration through the nose. This process allows the
medicine to bypass the digestive system, and may, in certain cases, allow
smaller does to be used to achieve the same results or orally ingested or
injected medicines. In some cases, it provides a delivery technique that
reduces side effects for medicines taken by other medicines.
lnhaler devices typically deliver their medicinal in a liquid
mist or a powder mist. The liquid mist is typically created by a
chlorofluorocarbon propellant. However, with the ban on
chlorofluorocarbons by the Montreal protocol, interest has tumed to dry
powder inhalers.
For a dry powder inhaler to work effectively, it must deliver
fine particles of medicinal powder that do not agglomerate, and do not end
up striking, and being absorbed by the patient's mouth or upper
oropharyngeal region. Air flow must therefore not be too fast. Furthermore,
it should not be difficult for a patient to load with medicine or to use with
the
proper technique. Current dry particle inhalers fail in one or more of these
important criteria.
SUMMARY OF THE INVENTION
Described is a dry powder inhaler comprising an intake
section; a mixing section, and a mouthpiece. The mouthpiece is connected by
a swivel joint to the mixing section, and may swivel back onto the intake
section and be enclosed by a cover. The intake chamber comprises a special
piston with a tapered piston rod and spring, and one or more bleed-through
orifices to modulate the flow of air through the device. The intake chamber
further optionally comprises a feedback module to generate a tone indicating
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to the user when the proper rate of airflow has been achieved. The mixing
section holds a capsule with holes containing a dry powder medicament, and
the cover only can open when the mouthpiece is at a certain angle to the
intake section. The mixing section further opens and closes the capsule when
the intake section is at a certain angle to the mouthpiece. The mixing section
is a Venturi chamber configured by protrusions or spirals to impart a cyclonic
flow to air passing through the mixing chamber. The mouthpiece includes a
tongue depressor, and a protrusion to contact the lips of the user to tell the
user that the DPI is in the correct position. An optional storage section,
with a
cover, holds additional capsules. The cover for the mouthpiece, and the
cover for the storage section may both be transparent magnifying lenses.
In one aspect, the present invention provides a medicament capsule
for an inhaler wherein the medicament capsule comprises holes in the
capsule to admit air flow and wherein structures in the interior surface of
the
capsule in use create cyclonic air flow.
In another aspect, the invention provides a medicament capsule for an
inhaler, comprising at least one keying surface to align the capsule in the
inhaler, wherein the keying surface comprises a protrusion or a slot which
enables identification of the capsule, or mates with a complementary keying
surface in the inhaler.
A method of making a capsule is also provided.
The capsules may be two-part capsules where each portion has holes
which correspond to holes in the other half when each half is partially fitted
to
the other half, and fully fitted to the other half. All the holes may be
closed
when the two halves are rotated around their longitudinal axes with respect to
each other. Each capsule may have a unique key on each half that only fits
with a particular inhaler.
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BRIEF DESCRIP77ON OF THE
SEVERAL VIEWS OF THE DRAWINGS
Figwe I is a schematic view of the dry particle inhaler descnbed
herein.
Figure 2 is schematic view of the mouthpiece cover.
Figure 3 is schematic view showing the angle between the intake
section and the mouthpiece.
Figure 4 is a schematic view of the dry particle inhaler, showing the
storage section.
Figure 5 is a schematic view of the intake section of the dry particle
inhaler, showing the fiow regulator and ihe feedback module.
Figure 6 is a schematic view of the mixing section.
Figure 7 is a schematic view of a capsule to hold medicament.
Figure 8 is a schematic view of the mouthpiece.
Figure 9 is a perspective view of a specific embodiment of the dry
particle inhaler in the closed position, with a capsule inserted into the
mixing
section, and extra capsules stored in the storage section.
Figure 10 is a perspective view of a specific embodiment of the dry
particle inhaler showing a capsule being loaded in to the nzixing section.
Figure 11 is a perspective view of a specific embodiment of the dry
particle inbaler showing a capsule inserted into the mixing section, and the
mouthpiece extended for use.
Figures 12, 13, 14, and 15 follow eacb other in temporal sequence.
Figure 12 is a perspective view of a specific embodiment of the dry
particle inhaler showing a closed mouthpiece cover.
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Figure 13 is a perspective view of a specific embodiment of the dry
particle inhaler showing an open mouthpiece cover.
Figure 14 is a perspective view of a specific embodiment of the dry
particle inhaler showing an open mouthpiece cover, an open mixing section
cover, and a capsule about to be inserted into the mixing section.
Figure 15 is a perspective view of a specific embodiment of the dry
particle inhaler showing the mouthpiece extended for use.
Figure 16 is a view of a pneumatic circuit, where air flows (fluid
flows) are represented by their electrical equivalents.
Figure 17 is a schematic view of the dry particle inhaler.
Figure 18 is a cutaway view of a capsule and a portion of the mixing
section.
Figure 19 is a cutaway view of half of a capsule, showing a cone in
the interior and a secondary hole with a chamfered, or beveled, edge.
TABLE OF REFERENCE NUMBERS
dry powder inhaler device
intake section
mixing section
mouthpiece
air passage through dry powder inhaler device
longitudinal axis of intake section
longitudinal axis of mouthpiece section
swivel joint connecting mouthpiece and mixing section
cover for mouthpiece
100 protrusions on mouthpiece cover
110 depressions on dry particle inhaler cover to mate with protrusions on
mouthpiece cover
120 tongue depressor on mouthpiece
130 protrusion on surface of mouthpiece to contact lips of device user =
135 opening of mouthpiece to be fitted into user's mouth
140 intake port
150 flow regulator
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160 bleed orifice
170 piston
180 piston head
190 piston rod
200 proximal portion of piston rod
210 distal portion of piston rod
220 spring
230 inner walls of intake section inner chamber
240 feedback module
250 mechanical fasteners in storage section
260 holder in mixing section for capsule
270 Venturi chamber
280 spiral shape or protrusions to impart cyclonic flow to air
290 cover for mixing chamber
291 interior of mixing section
292 air flow entrance to mixing section
294 air flow exit from mixing section
296 latch mechanism for mixing section cover
298 interior wall of mixing section
300 capsule
310 first tube
320 open end of first tube
330 closed end of first tube
340 long axis of first tube
350 protrusion on first tube
360 keying surface on first tube
370 secondary holes in first tube
372 chamfered edge of secondary hole
375 cone in interior of first tube
380 second tube
390 open end of second tube
400 closed end of second tube
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410 long axis of second tube
420 'protrusion on second tube
430 keying surface on second tube
440,, secondary holes in second tube
445 corie in interior of second tube
450 hand of user
460 air flow direction
4761' storage section
, ,f
480 storage section cover
DETAILED DESCRIPTION OF THE INVENTION
Figure 1 is a schematic drawing of the dry powder inhaler
(10) described herein. It comprises an intake section (20), a mixing section
(30) and a mouthpiece (40). An air passage (50) goes through the intake
section (20), a mixing section (30) and a mouthpiece (40). A swivel joint
(80) connects the mouthpiece (40) to the mixing section (30). The mixing
section (20) has a cover (290) which may be a transparent magnifying lens.
Arrow (460) shows the direction of air flow through the air passage (50)
through the dry powder inhaler (10).
Figure 2 shows the mouthpiece cover (90) in the closed
position over the dry particle inhaler (10). Protrusions (100) on the
mouthpiece cover (90) mate with grooves or depressions (110) on the dry
particle inhaler (10), to join the mouthpiece cover (90) to the dry particle
inhaler (10).
Figure 3 is a schematic of the showing the mouthpiece (40)
and the intake section (20) as represented by the longitudinal axis of the
mouthpiece (70) and the longitudinal axis of the intake section (60). The
swivel joint (80) connecting the mouthpiece (40) to the intake section (20) at
the mixing section (30) may be regarded as the vertex of the angle. The
importance of the angle (here called theta) between these two longitudinal
axes will be further explained.
Figure 4 shows the dry particle inhaler (10) with a storage =
section (470). Indicated as being inside the storage section (470) are
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mechanical fasteners (250) which operate to hold medicament capsules (300)
(not sbown in this Figure) in the storage section. In this embodiment, the
storage section (470) is shown as appended to the intake section (20). The
storage section has a cover (480) which may be a transparent magnifying
lens, to allow the user to easily read writing on medicament capsules stored
therein. The storage section cover (480) may swivel outward, or slide open
on a track (not shown), or open by a variety of inechanisms known to those
of skill in the art.
Figure 5 shows the intake section (20) of the dry particle
inhaler (10). The direction of air flow is shown by the arrow (460). Air is
admitted through an intake port (140) and one or more bleed orifices (160)
[The bleed orifices may also be styled as secondary ambient air intake ports].
The piston (170) normally covers the intake port (140). When the user (not
shown) inspires, the piston head (180) is drawn backwards, at a steady rate
modulated by the spring (220). The spring (220) is fixed to the piston (170)
and the inner wall (230) of the intake section chamber. Thus the rate of air
flow is controlled. The air flow is further controlled by the tapering of the
piston rod (190), past which the air flows. For further control of the air
flow,
a second spring (not shown) may also control the rate of movement of the
piston (170).
The piston (170) and spring (220) combination allow the user (not
shown) to generate a vacuum in his lungs before the intake port (140) opens.
Thus, by the time enough vacuum is generated to open the intake port (140),
there will be sufficient air flow at a sufficient rate in the dry particle
inhaler
(10) to draw most of the medicament in the capsule (not shown) out of the
inhaler into the proper place in the lungs of the user.
A feedback module (240) generates a signal to the user (not shown),
which tells the user whether he is inspiring at the correct rate. The signal
may
be an audible one, in one embodiment a tone that is at a steady pitch when air
flow is at a certain steady rate. In one embodiment of the dry particle
inhaler
(10), the signal is generated mechanically, such as be a musical reed. In
another embodiment of the invention, the signal might be generated
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electronically, after electronic measurement of the air flow rate. The
feedback module (240) would include a means for increasing or lessening the
signal strength, or turning the signal off entirely. If the signal were
generated
by a reed, the mechanism for turning off the signal might be covering a bleed
orifice which might admit the air flow generating the signal. If the signal
were generated electronically, a simple push button or dial might turn on and
off the signal.
Figure 6 shows a schematic of the mixing section (30) of the
present,invention. The mixing section has a cover (290), and a holder (260)
for a medicament capsule (not shown). The holder (260) is a mechanism
which grips and turns the capsule (not shown) to open and close it as the
longitudinal axis (70) of the mouthpiece is rotated about the swivel joint
(80)
relative to the longitudinal axis (60)of the intake section. Such a mechanism
may be straightforward: in a simplest embodiment, both the top and bottom
halves (not shown) of the capsule could be fixed to their respective holders
(260).
The Venturi chamber (270) speeds the flow of air near the
capsule (not shown). Air flows in at (292), and out through (294). In one
embodiment, air flows both through and around a capsule (not shown)
holding a dry powder medicament. The special shape of the Venturi
chamber (270), which further includes protrusions or spiral shapes (280),
imparts a cyclonic flow to the air passing through the mixing section (30).
This helps to de-agglomerate particles of dry powder. The spiral shape of
the interior of the mixing section (291) can be two separate spirals, in one
embodiment of the invention. Mixing section (30) therefore provides the
means whereby air flow is speeded up to suspend dry particles in air and de-
agglomerate them, and then slow the air flow somewhat while the particles
are still suspended in air. The cover (290) for the mixing section (30) may
be a transparent magnifying lens, so that any writing on the capsule (not
shown) may be read easily.
In one embodiment of the dry particle inhaler (10), the cover
(290) of the mixing section may not be opened unless the longitudinal axis
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(70) of the mouthpiece forms a certain angle with the longitudinal axis (60)
of the intake section, with the vertex of the angle being the swivel joint
(80)
connecting the mouthpiece (40) and the mixing section (30). The latch
mechanism (296) for the cover (290) of the mixing section can accomplish
this, by any of several mechanical means known to those of ordinary skill in
the art. In the simplest embodiment, a catclunent (not shown) in the cover
(290) for the mixing chamber would be engaged by a slip ring (not shown)
on the mixing section which was only a certain number of degrees of a circle.
When the mouthpiece (40) were rotated enough relative to the intake section
(20), the slip ring (not shown) would no longer engage the catchment (not
shown). In one embodiment, the user could open the cover (290) when the
angle were between approximately ninety and one-hundred and eighty
degrees.
Figure 7 shows a medicament capsule (300) for use with an
inhaler, be it a dry powder inhaler (10), or a liquid mist inhaler. The
capsule
(300) has two halves which fit together, here styled a first tube (310) and a
second tube (380). Each tube has an open end (320, 390), and a closed end
(330, 400). Each tube also has a long axis (340,410). In addition, each tube
has a number of secondary holes (370,440). The first tube (310) fits inside
the second tube (380) snugly. A protrusion (350) on the outer surface of the
first tube (310) can slide past a corresponding protrusion (420) on the inner
surface of the second tube (380). This locks the first tube (310) to the
second
tube (380). Therefore the first tube (310) and the second tube (380) have
both an unlocked and a locked position. In the unlocked position, at least
one secondary hole (370) in the first tube aligns with at least one secondary
hole (440) in the second tube. This pennits introduction of a medicament
(not shown) into the capsule through the aligned secondary holes (370, 440).
The first tube (310) may then be locked to the second tube (380). When a
user (not shown) is ready to use a capsule (300), he simply places it in the
holder (260) in the mixing section (30), and closes the cover (290). When
the holder (260) rotates the first tube (310) around its long axis (340)
relative
to the second tube (380) and its long axis (410) (the axes are now
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coincident), that causes at least two secondary holes (370) in the first tube
to
align vaith at least two secondary holes (440) in the second tube. Air can
now pass in, through, and out of the capsule (300), releasing the medicament
contained, t4erein. In one embodiment of the inhaler, the capsule (300) might
open when the angle between the longitudinal axis (70) of the mouthpiece
section, th,e vertex of the swivel joint (80), and the longitudinal axis (70)
of
the mouthpiece section were between one hundred and seventy and one-
hund~ed and eighty degrees. This rotation of the mouthpiece (40) relative to
thei,nta~e sectibn (20) would cause a corresponding rotation of the first tube
(310) about its long axis (340) relative to the second tube (380) and its long
axis (410).
1n one embodiment of the invention, several protnasions on the
surfaces of the first tube or the second tube might provide a variety of
locking positions. Similarly, a variety of secondary holes in the first and
second tubes might provide a variety of rotational positions aligning or not
aligning secondary holes on the first and second tubes.
The capsules described herein permit the introduction of liquid or gel
medicament which can be dried in the capsule, creating a powder. This
permits the accurate production of very small amounts of powdered
medicament in a capsule, since it can be formed from a larger volume of
accurately metered liquid or gel medicament. This permits very accurate
microdosing. In addition, chemical reactions and drug mixtures may be
made directly in the capsules described herein, then the resulting fonnulation
dried.
In one embodiment of the capsule (300), one or more of the
secondary holes (370, 440) used to admit air to the capsule is oval-shaped
(elliptical). In one embodiment of the invention, the ratio of the long axis
of
the ellipse to the shorter axis may be between 1:1 and 3:1, and may be 2:1.
This ratio may be called a vertical aspect ratio. In one embodiment of the
invention, the intersection of the surface defining one or more of the
secondary holes (370, 440) and the surface defining the interior of the
CA 02542640 2000-07-21
capsule (300) meet in a chamfered, or beveled, edge. This chamfered edge
creates a vortex when air flows through the secondary holes (370, 440).
Each capsule (300) also has a keying surface (or fastening
mechanism), on the closed end (330) of the first tube and the closed end (400)
of the second tube comprising the capsule. The keying surface (360) on the
first tube may be different from the keying surface (430) on the second tube.
That permits easy tactile and visual identification of the orientation of the
caps~,}le. It also permits a system where each drug fon~nulation in a capsule
~
(300) coxresponds to a dry particle inhaler (10), so users cannot mix up
drugs. In one embodiment of the invention, the keying surface (360) of the
first tube mates with a keying surface (430) of a different second tube, or
the
mechanical fas,teners (250) of the storage section (470). This permits easy
storage of the capsules (300) in the storage section (470).
Figure 18 shows a medicament capsule (300), with a keying surface
(360) on the first tube and a keying surface (430) on the second tube. It also
shows a cutaway view of the mixing section (30) and the air flow entrance
(292) to the mixing section and the air flow exit (294) to the mixing section.
A spiral shape (280) is given to the interior walls (298) of the mixing
section,
to impart a cyclonic flow to air passing through. The air ilow entrance (292)
and air flow exit (294) in this embodiment are tangential to the imaginary
tube we might call the mixing section interior (291). That is to say, if a
radius were drawn perpendicular to the long axis of the tube, and a tangent
line were drawn to the circle perpendicular to the radius, the air flow would
exit the mixing section along that tangent line. The tangential air flow exit
(294) increases the velocity of the air flow, and thus helps disperse the
medicament particles. As can be seen from Figure 18, the mixing section
interior (291) is sized to accommodate a medicament capsule (300). Keying
mechanisms (360, 430) are shaped to mate with holder (260) in the mixing
section. Capsules according to the present invention may have a number of
shapes, including ovoid and rectangular shapes. A variety of shapes of
protrusions and slots may also be employed as keying surfaces. For instance,
a keying surface might be a rectangular block, and a capsule holder might
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have a rectangular orifice. Altematively, a keying surface might be
triangular, hexagonal, Z-shaped, C-shaped, etc., and the holder would have
the correspondingly shaped aperture.
'. Figut;e 18 also shows one embodiment of the capsule (300) where a
cone (375) is located in the interior of the first tube, and a cone (445) is
located in the interior of the second tube. These cones (375, 445) cause the
air flow within the capsule to be cyclonic, aiding in mixing the medicament
partic,Jes with the air. A cone is shown herein, but other cyclone-creating
structures are contemplated by the present invention.
Figure 8 shows the mouthpiece (40) of the dry particle inhaler (10).
It has a protrusion (130) on its surface to contact the lips of a user (not
shown). This llelps the user place the mouthpiece correctly in his mouth.
The mouthpiece (40) also includes a tongue depressor (120), which may
have a bulbous shape. The mouthpiece (40) is long enough that it fits
approximately midway into the user's mouth (not shown). This permits
greater delivery of medicament to the lungs, and less delivery to the oral
cavity. The mouthpiece (40) has a particular aspect ratio of its inner channel
(50) (see Figure 17). This slows the air passing througb the channel so that
the air borne particulates do not end up striking the back of the user's
throat.
However, the air is not slowed so much that the particulates settle out of the
air flow.
Figure 9, Figure 10, and Figure 11 show one specific
embodiment of the dry particle inhaler (10). In Figure 9, the cover (90) of
the mouthpiece is closed, and several capsule (300) are in the storage section
(470). In Figure 10, the mouthpiece (40) has been rotated relative to the
intake section (20). The longitudinal axis (60) [not sbown] of the intake
section here makes an approximately ninety degree angle with the
longitudinal axis (70) of the mouthpiece section. This permits the cover
(290) for the mixing section to be opened. A medicament capsule (300)
taken from the storage section (470) is about to be inserted into the mixing
section (30). In Figure 11, the mouthpiece (40) has been rotated to a fully
extended position, the cover (290) for the mixing section has been closed,
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and the dry particle inhaler 910) is ready for use. In one embodiment of the
dry particle inhaler (10), when the dry particle inhaler is in the closed
position (Figure 9), the interior of the intake section (20) would be isolated
from the obtside air, but the mouthpiece (40) interior and the mixing section
interior (291) would not be, permitting them to dry out after being exposed to
the humid breath of a user.
Figure 12, Figure 13, Figure 14, and Figure 15 show a
õl
te,Mporal sequence where a capsule (300) of inedicament is loaded into the
miicingsection (
, 30) of a dry particle inhaler (10), and the mouthpiece (40) s
~~ i
extended Kfor i8e. The dry particle inhaler (10) described herein can also be
used for nasal delivery of medicaments. A small tube (not shown) can be
Yi
fitted to the end of the mouthpiece (40), and the other end of the tube
inserted into the nostril_ Alternatively, the mouthpiece (40) may be replaced
by a nosepiece (not shown), whose free end is sized to be inserted into a
nostril of a user. In another embodiment, a device such as a bellows or a
syringe is used to force air through the dry particle inhaler (10) into a
nosepiece inserted into the nostril of a user (not shown).
Figure 16 shows the fluid (air) flow of the dry particle inhaler
(10) modeled as the equivalent electrical circuit. This is styled a "pneumatic
resistance circuit".
Figure 17 shows a schematic view of the dry particle inhaler
(10). The air passage (50) through the dry particle inhaler widens as it goes
through the mouthpiece (40) along the direction of the air flow (460). The
opening (135) of the mouthpiece to be inserted into the mouth of the user
may be roughly ellipsoid, or oval, and thus have a major axis and a minor
axis. The ratio of these two may be called the horizontal aspect ratio. In one
embodiment of the invention, the horizontal aspect ratio is between 2:1 and
4:1. In one embodiment of the dry particle inhaler (10), the horizontal aspect
ratio is 3:l . Shaping the opening (135) in this manner keeps the drug
particles collimated, maintains the optimal velocity'of the particles in the
air
stream, and is oriented to the natural horizontal aspect ratio of the
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CA 02542640 2007-02-05
oropharyngeal region of the mouth. In one embodiment of the invention, the
outline of the opening (135) resembles a bean.
The dry particle inhaler described herein may be used with
medicament particles of low, medium, and high shear forces.
The dry particle inhaler and capsules described herein may be made
with a variety of suitable materials known to those skilled in the art, such
as
metal, glass, rubber, and plastic.
While the invention has been described with reference to particular
embodiments, those skilled in the art will be able to make various
modifications without departing from the scope thereof.
14
