1
F O R M 2
THE PATENTS ACT, 1970
(39 of 1970)
&5
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
10
1. Title of the invention. –
BREATH ACTUATED INHALER
15
2. Applicant(s)
(a) NAME : LUPIN LIMITED
20
(b) NATIONALITY : An Indian Company
(c) ADDRESS : Kalpataru Inspire, 3rd Floor, Off Western Express
Highway, Santacruz (East), Mumbai – 400 055,
Maharashtra, India25
3. PREAMBLE TO THE DESCRIPTION
30
The following specification particularly describes the invention and the manner in
which it is to be performed :
35
2
FIELD OF THE INVENTION
The present invention relates to a breath actuated metered dose inhaler. The
invention further provides modified version of a diaphragm and a flap for a trigger
mechanism of a breath actuated metered dose inhaler. The invention further5
provides methods for manufacturing the same.
BACKGROUND TO THE INVENTION
There are a variety of inhalation devices which release aerosol medication, either10
in a continuous spray or in a predetermined amount. Examples of such inhalation
devices includes pressurized metered-dose inhaler (pMDI) and dry-powder inhaler
(DPI). Generally, pMDIs are comprised of three major components; an aerosol
canister where the formulation resides for administration to the lungs, a metering
valve which is disposed in the canister and which allows a metered quantity of the15
formulation to be dispensed with each actuation, an actuator which holds the
canister and allows the patient to operate the device and directs the aerosol into the
patient's lungs. Most common in this category are “press and breathe” type pMDI
inhalation devices and these devices are actuated by the pressure applied by the
user's fingers, button action, or other related manual techniques. In use a “puff” or20
single dose of the stored formulation is metered and delivered when the patient
depresses the canister within the actuator.
A more recent development is the so-called “breath actuated inhaler” which delivers
a dose of drug through a mouthpiece in response to inhalation by the user. Breath25
actuated inhalers are preferred in circumstances where the co-ordination between
user inhalation and manual depression of the aerosol canister is imperfect. For
example, children or elderly patients have difficulty in synchronising actuation of
the MDI with inhalation or sometimes patient breathes out before inhalation is
complete.30
3
PCT application WO 01/93933 A2 describes such breath-actuated metered dose
inhaler. A preload is applied to the internal aerosol valve by an amount sufficient
to result in a dose release, but this is prevented by the application of a pneumatic
resisting force. Inhalation causes the releases of the pneumatic resisting force and
allows the preload to actuate the aerosol valve. The pneumatic resisting force is5
established by a negative pressure region defined in part by a diaphragm. The
diaphragm includes a central disk of a first, relatively high stiffness material and a
peripheral ring, coupled by a flexure of a second, relatively low stiffness material.
The diaphragm also includes a small valve port which is covered by a valve seal
(flap). A valve seal (flap) seals a valve port to create a pressure differential. On10
inhalation by the patient through the mouthpiece, the valve seal (flap) moved out of
a sealing position to open the valve port to break the pressure differential causing
the preload to actuate the aerosol valve.
U.S. Pat. No. 10,792,447 B2 describes a more recent breath-actuated metered dose15
inhaler. The patent discloses a modified structure of the valve port of the pneumatic
force holding unit which purportedly reduces the rate of degradation of the pressure
difference within a pneumatic force holding unit in a prepared configuration
causing reduced likelihood of accidental actuation facilitating patient compliance
and treatment outcomes.20
Although such devices have provided the advantage of being able to provide
improved breath actuated device, there remains room for improvement. Naturally
there is a need to develop breath actuated device that is efficient and robust. The
present invention improves the robustness of the device by retaining the vacuum25
within the diaphragm when the mouthpiece cover is left opened for an extended
time without being used as discussed herein. The present invention also improves
the ease of manufacture by using a simplified structure of the central rigid disk,
while improving robustness.
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4
SUMMARY OF THE INVENTION
In one embodiment, the present invention provides an improved breath actuated
inhaler device comprising an actuator housing, canister and a mechanical release
mechanism for triggering the dose in response to breathe. The mechanical release5
mechanism is similar to that of pneumatic force holding unit disclosed in PCT
application WO 01/93933 A2 but includes a structure that is distinct from and also
provides substantial improvement. The pneumatic force holding unit comprises a
compression spring (preload), a lower cap that engages the canister, a diaphragm
attached to an upper surface of the lower cap, and a flap to seal a valve port located10
in the diaphragm. The diaphragm includes a central rigid disk and a peripheral
flexible polymer ring.
In an embodiment, the present invention provides an improved breath actuated
inhaler device comprising an actuator housing, canister and pneumatic force15
holding unit comprising a compression spring (preload), a lower cap that engages
the canister, a diaphragm attached to an upper surface of the lower cap, and a flap
to seal a valve port located in the diaphragm. The diaphragm includes a central rigid
disk and a peripheral flexible polymer ring for triggering the dose in response to
breathe.20
In an embodiment, the present invention provides an improved breath actuated
inhaler device comprising an actuator housing, canister and pneumatic force
holding unit for triggering the dose in response to breathe.
25
In an embodiment, the present invention provides an improved pneumatic force
holding unit wherein a central rigid disk of the diaphragm is provided with the
interlocking means to firmly secure and bound the peripheral flexible polymer ring.
In an embodiment, the present invention provides an improved pneumatic force30
holding unit wherein a central rigid disk of the diaphragm is provided with the
5
interlocking means to firmly secure and bound the peripheral flexible polymer ring
with the central rigid disc of the diaphragm during injection molding of the
diaphragm.
The interlocking means are the one or more grooves or cavities. Preferably the5
interlocking means are between 1 to 25 in numbers, more preferably between 5-20
in numbers. The interlocking means are of same or different geometry and may or
may not be located equidistance from each other.
In an embodiment, a central rigid disk and a peripheral flexible polymer ring of10
diaphragm is formed by two shot injection molding process. In first shot the central
rigid disk is prepared having the interlocking means. In second shot a peripheral
flexible polymer ring of diaphragm is prepared. During the second shot injection
molding process the flexible polymer is allowed to flow through the interlocking
means of a central rigid disk to form a continuous uninterrupted part on either side15
of the central rigid disc of the diaphragm. This allows mechanical bonding of the
peripheral flexible polymer ring with the central rigid disc and at the same time
creates a strong adhesion with the central rigid disc. Further mechanical interlock
between a central rigid disk and a peripheral flexible polymer ring on the diaphragm
is prevented from being peeled off from the central rigid disc while the vacuum is20
being retained prior to inhalation.
In some aspects, the material which can be used to construct the central rigid disk
includes Acrylonitrile butadiene styrene (ABS), Polypropylene (PP), Polyethylene
(PE), Polytetrafluoroethylene (PTFE). In some aspects, the material which can be25
used to construct the flexible polymer ring includes Thermoplastic Polyurethane
(TPU), Silicone, and Thermoplastic Polyethylene (TPE).
The hardness of the central rigid disk 20 is typically between 80 -140 on R scale of
Rockwell hardness but preferably between 100 -120 on R scale of Rockwell30
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hardness. The hardness of the flexible polymer ring is typically between 55-75
Shore A, but preferably between 60-70 Shore A.
In an embodiment, the present invention provides an improved pneumatic force
holding unit having a diaphragm wherein a central rigid disk of the diaphragm is5
provided with the interlocking means to firmly secure and bound the peripheral
flexible polymer ring with the central rigid disc of the diaphragm during injection
molding of the diaphragm, wherein a central rigid disk and a peripheral flexible
polymer ring of diaphragm is formed by two shot injection molding process.
10
In an embodiment, the present invention provides an improved pneumatic force
holding unit having a diaphragm wherein a central rigid disk of the diaphragm is
provided with the interlocking means to firmly secure and bound the peripheral
flexible polymer ring with the central rigid disc of the diaphragm during injection
molding of the diaphragm, wherein a central rigid disk and a peripheral flexible15
polymer ring of diaphragm is formed by two shot injection molding process
wherein the central rigid disk is prepared having the interlocking means in first shot
and a peripheral flexible polymer ring of diaphragm is prepared in second shot
during which flexible polymer is allowed to flow through the interlocking means of
a central rigid disk to form a continuous uninterrupted part on either side of the20
central rigid disc of the diaphragm.
In a further aspect of an embodiment, the invention provides a flap to seal a valve
port of the diaphragm wherein the flap consists of a rigid component and the soft
elastomer component wherein a soft elastomer component forms an air tight lock25
with the valve port of the diaphragm. The hardness of the soft elastomer component
is between 10-20 Shore A and preferably between 12-16 Shore A.
In an embodiment, the present invention improves the robustness of the device by
retaining the vacuum within the diaphragm when the mouthpiece cover is left30
opened for an extended time without being used, for at least about 5 Minutes,
7
preferably at least about 10 minutes, more preferably at least about 15 minutes,
more preferably at least about 25 minutes. The mechanical interlock between a
central rigid disk and a peripheral flexible polymer ring on the diaphragm is
prevented from being peeled off from the central rigid disc while the vacuum is
being retained prior to inhalation. Further the flap forms an airtight seal with the5
valve port of the diaphragm thereby preventing the leak. When the mouthpiece
cover is left opened, the device remained in the actuable condition without firing
the dose for at least about 5 minutes, preferably at least about 10 minutes, more
preferably at least about 15 minutes, more preferably at least about 25 minutes. The
force retained by the pneumatic force holding unit degrades by less than about 6%10
over a period of 5 minutes, preferably less than about 3%, preferably from about
2.7% to about 1%; 1.5% being an example.
FIGURES:
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Fig. 1 shows a partial-exploded isometric view of the breath-actuated inhaler
device.
Fig. 2 shows a partial-exploded isometric view of the breath-actuated inhaler
device showing exploded view of pneumatic force holding unit.
Fig. 3 shows an isometric view of diaphragm according to the invention.20
Fig. 4 shows an isometric view of a central rigid disk of diaphragm according to
the invention.
Fig. 5 shows an isometric view of a peripheral flexible polymer ring of diaphragm
according to the invention.
Fig. 6 shows an isometric view of a flap according to the invention.25
DETAILED DESCRIPTION OF THE INVENTION:
The present invention provides a modified version of a diaphragm and a flap for a
trigger mechanism of a breath actuated metered dose inhaler and the methods for30
manufacturing the same.
8
Fig. 1 shows a partial-exploded isometric view of the breath-actuated inhaler device
having top housing 40 and bottom housing 30. The inhaler device houses a canister
31 containing a medicament to be dispensed.
5
Fig. 2 shows a breath-actuated inhaler device showing exploded view of pneumatic
force holding unit. The pneumatic force holding unit showing a canister support
sleeve 32, a spring 35, a diaphragm 33, a diaphragm retaining ring 34, a flap 37, a
flap spring 36, a flap housing 38, a cloth filter 39. The canister support sleeve 32
encases and drives the canister 31. The spring 35 is in compressed position when10
the mouthpiece cover 301 is in closed position as can be seen in this figure. The
diaphragm 33 is held in place over the canister support sleeve 32 by a diaphragm
retaining ring 34 that snaps over the canister support sleeve 32. The spring 35 is a
compression spring located between the flange of the flap housing 38 and the flat
bearing surface of the diaphragm retaining ring 34. The flap housing 38 bears15
features to situate the flap component 37 and the flap spring 36. The flap spring 36
biases the flap 37 over the open valve port 204 (Fig. 3) of the diaphragm 33. A cloth
filter 39 is welded over the flap housing 38. The pneumatic force holding unit is
located inside the top housing 40.
20
Fig. 3- Fig. 5 shows an isometric view of diaphragm 33 according to the invention
having central rigid disk 20 and a peripheral flexible polymer ring 10. Fig. 4 shows
an isometric view of a central rigid disk 20 of diaphragm according to the invention
and Fig. 5 shows an isometric view of a peripheral flexible polymer ring 10 of
diaphragm according to the invention. The central rigid disk 20 has circumferential25
openings 201, transverse baffle 202, boss 203, valve port 204 and radial rib 205.
The transverse baffle 202 helps direct the air flow over the flap 37 (Fig. 2 and Fig.
6) during inhalation. The valve port 204 is closed and sealed by the flap 37 prior to
inhalation. The boss 203 surrounding the valve port 204 provides a guided passage
for the air to escape during inhalation. The radial rib 205 supports the boss 203 and30
facilitates the molding process by providing a connection between the boss 203 and
9
the transverse baffle 202, allowing all structures of the central rigid disk 20 to be
molded in a single injection shot. The circumferential openings 201 allow the
flexible polymer to pass through during the molding process creating a mechanical
bond between the two components. The central rigid disk 20 and a peripheral
flexible polymer ring 10 of diaphragm is formed by two shot injection molding5
process. In first shot the central rigid disk 10 is prepared having the circumferential
openings 201 which acts as an interlocking means. The circumferential openings
201 are between 1 to 25 in numbers, more preferably between 5-20 in numbers and
are of same or different geometry and may or may not be located equidistance from
each other. The material which can be used to construct the central rigid disk10
includes ABS, PP, PE, PTFE. The hardness of the central rigid disk 20 is typically
between 80 -140 on R scale of Rockwell hardness but preferably between 100 -120
on R scale of Rockwell hardness. In second shot a peripheral flexible polymer ring
10 of diaphragm is prepared. During the second shot injection molding process the
flexible polymer is allowed to flow through the circumferential openings 201 of a15
central rigid disk 10 to form a continuous uninterrupted part on either side of the
central rigid disc 20 of the diaphragm. This allows mechanical bonding of the
peripheral flexible polymer ring 10 with the central rigid disc 20 and at the same
time creates a strong adhesion with the central rigid disc 20. Further mechanical
interlock between a central rigid disk 20 and a peripheral flexible polymer ring 1020
on the diaphragm 33 is prevented from being peeled off from the central rigid disc
20 while the vacuum is being retained prior to inhalation especially in the extended
(stressed) state. The advantage of this particular arrangement is that in addition to
the chemical bond created during the two shot molding process, the mechanical
bond provides addition security of the two components especially while the vacuum25
is being retained prior to inhalation especially in the extended (stressed) state. The
material which can be used to construct the flexible polymer ring includes TPU,
Silicone, TPE. The hardness of the flexible polymer ring is typically between 55-
75 Shore A, but preferably between 60-70 Shore A.
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10
Fig. 6 shows an isometric view of a flap according to the invention. The flap 37
consists of a rigid component 371 and the soft elastomer 372. The flap 37 is formed
as a two shot part during injection molding process. The soft elastomer 372 forms
an air tight seal with the valve port 204 (Fig. 3) of the central rigid disc 20 of the
diaphragm 33 when the flap spring 36 is biased on the flap 37. In use, the air flow5
by a patient causes the flap 37 to bias against the flap spring 36, thereby opening
the valve port 204 on the rigid component 20 of the diaphragm 33. The material
which can be used to construct the rigid component 371 includes ABS, POM or
PTFE. The material which can be used to construct soft elastomer 372 includes
TPU, TPE or Silicone. The hardness of the soft elastomer 372 is typically between10
5-20 on Shore A, but preferably between 12-16 Shore A to allow enough flexion of
the elastomer 372 over the valve port 204.
When in use, once the mouthpiece cover 301 of the bottom housing 30 is opened,
the spring 35 extends partially and pushes the canister support sleeve 32 via the15
diaphragm ring 34. This causes the peripheral flexible polymer ring 10 of the
diaphragm 33 to extend. The valve port 204 on the central rigid disc 20 of the
diaphragm 33 is closed by the flap 37 biased by the flap spring 36. This prevents
the complete extension of the spring 35 due to negative pressure build up between
the diaphragm 33 and the canister support sleeve 32. The diaphragm 33 of the20
present invention is advantageous as it helps in retaining the vacuum in this
extended (stressed) state for a longer period due to both chemical bond and
mechanical bond created during the two shot molding process. This effect is further
amplified and/or maintained by the soft elastomer 372 of a flap 37 which forms an
air tight seal with the valve port 204 and thereby preventing vacuum leak. The25
present invention improves the robustness of the device by retaining the vacuum
within the diaphragm 30 and canister support sleeve 32 when the mouthpiece cover
is left opened for an extended time without being used, for at least about 5 Minutes,
preferably at least about 10 minutes, more preferably at least about 15 minutes,
more preferably at least about 25 minutes. The mechanical interlock between a30
central rigid disk and a peripheral flexible polymer ring on the diaphragm is
11
prevented from being peeled off from the rigid disc while the vacuum is being
retained prior to inhalation. When the mouthpiece cover is left opened, the device
remained in the actuable condition without firing the dose for at least about 5
minutes, preferably at least about 10 minutes, more preferably at least about 15
minutes, more preferably at least about 25 minutes. The force retained by the5
pneumatic force holding unit degrades by less than about 6% over a period of 5
minutes, preferably less than about 3%, preferably from about 2.7% to about 1%:
1.5% being an example. When the user inhales, the air enters the device through the
vents 401 on the top housing 40. The air flow causes the flap 37 to bias against the
flap spring 36, thereby opening the valve port 204 on the central rigid disc 20 of the10
diaphragm 33 thereby causing a complete vacuum release. This results in complete
extension of the spring 35 and the actuation of the canister 31 release of the dose.
Evaluation of the pneumatic force holding unit performance in breath actuated
inhalers is done by measuring the ability of the pneumatic force holding unit in15
retaining a pressure difference after priming over a time testing period, typically 5
minutes. The instrument used was Texture Technologies’ Texture Analyzer
TA.XTPlus. The widest force probe was attached to the 50kg load cell of the
texture analyzer. The pneumatic force holding unit is placed underneath the force
probe on the texture analyzer base. The probe was moved downward at a speed of20
0.25 mm/s until force reading of 90 N. The probe was retracted 2.6mm above the
current position at a speed of 10mm/s. As soon as the probe retracted 2.6mm, the
force is recorded as F1. The force probe was allowed to remain in that position for
a period of 5 minutes. After 5 minutes have elapsed, the force is recorded as F2.
The data was used to calculate the change in force (Delta F (F1-F2)) as well as the25
percentage change over a period. The results are summarized in Table 1.
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Table 1
Pneumatic Force
Holding Unit
Test
Number
F1 (N) F2 (N) Delta F (N) % Change
Device 1 1 27.24 27.96 0.715 2.626%
2 26.95 27.49 0.539 2.000%
3 26.54 27.14 0.598 2.253%
Device 2 1 28.14 28.64 0.491 1.743%
2 28.07 28.36 0.294 1.049%
3 28.01 28.48 0.471 1.681%
Device 3 1 30.30 31.10 0.794 2.620%
2 29.42 29.94 0.519 1.765%
3 28.84 29.53 0.686 2.379%
As can be seen from the data of table 1, pneumatic force holding unit of breath
actuated inhaler according to the present invention improved the robustness of the
device by retaining the vacuum within the diaphragm when the mouthpiece cover5
is left opened for an extended time without being used a patient and thus improves
the patient compliance. Surprisingly, such improvements may be achieved even
when employing a valve seal (flap) surface having a roughness average that is
greater than the 0.15 μm described as critical for retaining pneumatic force in the
prior art.10
15
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WE CLAIM:
1. A breath actuated inhaler device comprising:5
an actuator housing;
canister and;
a pneumatic force holding unit for triggering the dose in response to breathe;
wherein pneumatic force holding unit comprising a compression spring
(preload), a lower cap that engages the canister, a diaphragm attached to an10
upper surface of the lower cap, and a flap to seal a valve port located in the
diaphragm,
wherein the diaphragm includes a central rigid disk and a peripheral flexible
polymer ring for triggering the dose in response to breathe,
wherein the central rigid disk of the diaphragm is provided with the15
interlocking means to firmly secure and bound the peripheral flexible
polymer ring with the central rigid disc of the diaphragm.
2. The breath actuated inhaler device according to claim 1, wherein the flap
consists of a soft elastomer component to form an air tight lock with the20
valve port of the diaphragm.
3. The breath actuated inhaler device according to claim 1, wherein a central
rigid disk and a peripheral flexible polymer ring of diaphragm is formed by
two shot injection molding process.25
4. The breath actuated inhaler device according to claim 1, wherein the
hardness of the flexible polymer ring is between 55-75 Shore A.
5. The breath actuated inhaler device according to claim 2, wherein the30
hardness of the soft elastomer component is between 5-20 Shore A.
14
6. The breath actuated inhaler device according to claim 1, wherein a central
rigid disk of the diaphragm is provided with the interlocking means to firmly
secure and bound the peripheral flexible polymer ring with the central rigid
disc.5
7. A breath actuated inhaler device comprising:
an actuator housing;
canister and;
a pneumatic force holding unit for triggering the dose in response to breathe;10
wherein pneumatic force holding unit comprising a compression spring
(preload), a lower cap that engages the canister, a diaphragm attached to an
upper surface of the lower cap, and a flap to seal a valve port located in the
diaphragm,
wherein the flap consists of a soft elastomer component to form an air tight15
lock with the valve port of the diaphragm.
8. The breath actuated inhaler device according to claim 7, wherein the
hardness of the soft elastomer component is between 5-20 Shore A.
20