Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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A SUPPORT STRUCTURE FOR A MEDICAMENT
The present invention relates to a support structure for a medicament in the
form of, for example, a blister pack for a drug or an injection moulded drug
dosing
element as used in an inhalation device. A typical blister pack for a
medicament is
described in WO 01/45777 and a typical drug dosing element is described in US
5,590,645.
With powdered medicaments there is a demand for a package/support
structure which is able to keep the powder free from the ingress of moisture
both
during storage and when the powdered medicament has been loaded into a
delivery
io device. Similarly, if the drug is in tablet or capsule form there is also a
demand to
keep the tablets/capsules, which are typically held in a blister pack, free
from the
ingress of moisture. The main weakness in a support structure which has a lid
sealed to a base, having one or more cavities for holding the medicament, is
in the
region where the lid is sealed to the base. If the support structure is in the
form of a
1s blister pack, the lid and base are often both made from a material having
an
aluminium layer which makes these elements moisture impermeable. Accordingly,
the only region where moisture can penetrate the blister pack is through the
lid
sealing region which is typically a heat seal. If the base of the blister pack
is made
from a plastic material then there will also be moisture ingress through the
base
20 material to the medicament. If the support structure is in the form of an
injection
moulded dosing element, the injection moulded base will be made from a
moisture
permeable material whereas the lid will typically have an aluminium layer
making it
moisture impermeable. In this case, there will also be moisture ingress
through both
the heat seal between the lid and base and through the base material.
25 The problem of moisture ingress has been overcome to a certain degree in
prior art inhalation device components by using aluminium containing foil
materials
for both the lid and base and spacing adjacent cavities by approximately 3mm.
With
such a construction, moisture within an empty cavity does not then compromise
an
adjacent cavity which still contains a dose of medicament. The only weakness
so resides in the heat seal between lid and base. A disadvantage with this
construction
is that there is a limit to the number of doses which can be arranged on the
blister
pack/dosing element due to the spacing requirement.
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Other prior art solutions include providing a desiccant source which is
connected to or placed within a cavity containing the medicament. However,
this
solution is reactive only, in that moisture is removed after having penetrated
a cavity
rather than preventing moisture from entering the cavity in the first place.
Similarly,
an alternative solution has been to use a desiccant box inside an aluminium
bag
which holds a plurality of medicament doses, e.g., tablets, but this form of
moisture
protection is destroyed when the bag is opened for the first time so that
there is no in-
use stability. For further examples of prior art solutions, reference should
be made to
WO 03/61742 and US 6,132,394.
In view of the problems discussed above, the present invention seeks to
provide moisture protection for the medicament and to maximise the number of
doses arranged on the support structure.
According to the present invention, there is provided a support structure for
a
medicament comprising a base with at least one cavity for the medicament and a
lid
is for sealing the medicament within the cavity characterised in that each
moisture
permeable region of the structure is protected against the ingress of moisture
by
locating a moisture absorbing sink between that region and the ambient air
outside
.the structure.
Preferably, the sink reduces the relative humidity (RH) of the air passing
through it to substantially the relative humidity (RH) of the air within the
cavity so that
there is minimal diffusion of moisture from the sink to the cavity.
Preferably, each moisture permeable region comprises an inner moisture
permeable barrier located adjacent to the cavity and an outer moisture
permeable
barrier, the moisture absorbing sink being located between the inner and outer
barriers.
Preferably, the base and the lid are moisture impermeable and the moisture
permeable region of the structure is located where the lid is sealed to the
base.
Preferably, the moisture absorbing sink between the lid and the base is
spaced from the periphery of the cavity thereby forming an inner moisture
permeable
3o region and an outer moisture permeable region, the sink breaking the
moisture
ingress path so that there is minimal diffusion of moisture through the inner
moisture
permeable region to the cavity.
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Preferably, the moisture absorbing sink comprises a channel in the base
surrounding the cavity which contains dry air.
Preferably, there is provided a plurality of cavities each having a channel
filled
with dry air.
s Preferably, each channel is connected to a single desiccant source which
dries the air in all the channels.
Preferably, the moisture absorbing sink comprises a polymer ring surrounding
the cavity and located between the lid and the base.
Preferably, there is further provided a plurality of cavities each having a
io polymer ring.
Preferably, the base and the lid have an aluminium layer for moisture
impermeability, the lid being heat sealed to the base.
Preferably, the lid is moisture impermeable and the base material is moisture
permeable, the moisture permeable regions being located where the lid is
sealed to
15 the base and within the base material of the cavity walls.
Preferably, a first moisture absorbing sink is located between the lid and the
base and is spaced from the periphery of the cavity and a second moisture
absorbing
sink is located within the base material of the cavity walls thereby forming
inner
moisture permeable barriers and outer moisture permeable barriers, the sink
2o breaking the moisture ingress path so that there is minimal diffusion of
moisture
through the inner moisture permeable barriers to the cavity.
Preferably, the moisture absorbing sink comprises a channel containing dry air
surrounding the cavity opening where the lid is sealed to the base and passing
through the cavity walls.
25 Preferably, there is further provided a plurality of cavities each having a
channel containing dry air.
Preferably, each channel is connected to a single desiccant source which
dries the air in all the channels.
Preferably, the base is injection moulded and the lid has an aluminium layer
30 for moisture impermeability, the lid being heat sealed to the base.
Preferably, the base comprises cooperating stackable elements, each element
having a plurality of cavities, the cavities within one of the elements
sifting between
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the cavities within another element when stacked, a moisture absorbing sink
being
formed by the spacing between the cooperating elements.
Preferred embodiments of the present invention will now be described in
detail, by way of example only, with reference to the accompanying drawings,
of
s which:
Figure 1 is a graphic representation of the relative humidity gradient across
a
barrier for a drug with conventional moisture protection;
Figure 2 is a graphic representation of the relative humidity gradient across
a
barrier arrangement with moisture protection according to the present
invention;
Figure 3 is a section through one blister in a blister pack with moisture
protection according to a preferred embodiment of the present invention;
Figures 4A, 4B and 4C depict preferred embodiments of blister packs with
multiple cavities having moisture protection;
Figure 5 is a plan view of a section of a dosing element for an inhalation
1s device having moisture protection according to a preferred embodiment of
the
present invention;
Figure 6 is a sectional view in direction X-X through the dosing element in
Figure 5;
Figure 7 depicts a further preferred embodiment of a dosing element having
moisture protection;
Figure 8 depicts the underside of annular ring 111 b in Figure 7; and,
Figure 9 is an enlarged view of part of the annular ring in Figure 8.
Reference should now be made to Figure 1 which depicts the relative humidity
(RH) gradient across a barrier which is moisture permeable. The barrier could
be, for
example, the material from which the base of the support structure is made or
the
heat seal between the lid and base of the support structure. The moisture
ingress
through the barrier arises because the relative humidity in the ambient air
outside the
support structure is typically 70% whereas the relative humidity of the air
and
powdered drug within a cavity is typically 20%. The moisture ingress arises
both
from the ambient air and from neighbouring cavities which have already been
emptied. The powdered drug is protected only by a single barrier and moisture
is
continually transported through the barrier by gradient driven diffusion. The
transport
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of moisture continues until the relative humidity inside a cavity reaches the
ambient
level. Moisture protection can only be improved by increasing the barrier
thickness or
modifying the properties of the barrier material.
In the present invention, it is proposed to locate a moisture absorbing sink
5 between each moisture permeable region of the support structure and the
ambient
air. This can be achieved, for example, by breaking the single barrier into an
outer
barrier and an inner barrier with the sink located between the two barriers.
Figure 2
depicts a preferred arrangement where the sink effectively breaks the moisture
ingress path. The relative humidity gradient across the outer barrier is high
giving
lo moisture diffusion as in Figure 1. However, when the moisture passes into
the sink
which has high moisture absorption qualities, any moisture diffusion through
the inner
barrier will be low. For example, if dry air is present in the sink, the
relative humidity
of the air in the sink could fall to 20% (which is a similar level to that
within the cavity)
with the result that the relative humidity gradient would be very low across
the inner
barrier and the moisture ingress path could be broken.
Figure 3 depicts a first preferred embodiment of the present invention where
the support structure is in the form of a blister pack 1 having a base 2 with
at least
one cavity 3 holding a medicament and a lid 4 which is sealed to the base 2 by
way
of heat seals 5 and 6. Between the outer seal 5 and the inner seal 6 is a
moisture
2o absorbing sink in the form of a channel 7 which surrounds the cavity 3. The
channel
7 could contain dry air to remove moisture in the region of the lid 4. The
moisture
ingress path M for this support structure will only be through the heat seals
5 and 6
as the blister pack base 2 and lid 4 would typically be manufactured from a
moisture
impermeable material having an aluminium component. The moisture ingress path
M
would result in a relative humidity gradient similar to that depicted in
Figure 2. The
outer barrier would be heat seal 5 and the inner barrier would be heat seal 6.
The
dry air in channel 7 would be dried by way of a desiccant. If the dry air
reduces the
relative humidity in the channel 7 to approximate(y 20% then there will only
be
minimal moisture diffusion through the heat seal 6 to the cavity 3 assuming
that the
so relative humidity within cavity 3 is also approximately 20%.
Reference should now be made to Figures 4A, 4B and 4C which depict three
configurations for a blister pack having a plurality of cavities 3. In Figure
4A each
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cavity 3 is surrounded by a dry air channel 7. The channels 7 are all
connected to a
desiccant 8 which ensures that air within the channels is continually dried to
the
required level. The channels and desiccant reservoir would typically be cold
formed
in the same manufacturing process step as the cavities. Figure 4B depicts a
further
s modification using a rectangular channel configuration. Figure 4C depicts a
preferred
configuration when the moisture absorbing sink for each cavity 3 is a moisture
absorbing material, e.g., a polymer in the form of a nylon ring 9. In this
case, there is
no need for a desiccant and each cavity 3 has a dedicated nylon ring which
sits
between the base 2 and lid 4 of the support structure.
In Figure 5, the support structure for the medicament is in the form of an
annular drug dosing element 101. This type of dosing element typically sits
within an
inhalation device which is able to index the drug cavities 103a, 103b and 103c
past a
mechanism which ruptures the lid 104 and allows the user to draw the drug from
each cavity. Figure 5 shows a segment of the annular dosing element 101
1s containing three adjacent cavities 103a, 103b, 103c. One of the cavities
103a is
empty whereas the other two cavities 103b and 103c still contain the powdered
drug.
Figure 6 is a sectional view taken in direction X-X through the dosing element
in
Figure 5.
The base 102 of the dosing element 101 would typically be injection moulded
2o and hence would be moisture permeable. With this arrangement, moisture
protection
is needed both where the lid 104 is heat sealed to the base 102 and within the
base
material. There are channels 107 running between adjacent cavities and beneath
each cavity through the base 102.
The channels 107 all connect to a desiccant 108 which dries the air in the
2s channels to reduce the relative humidity to that within the cavities.
For cavity 103b, the outer heat seal 105 runs around the outer and inner
peripheries of the annular dosing disc. There is also an outer moisture
barrier 109 in
the base 102. The channel 107 creates the inner barriers in the form of the
inner
heat seal 106 and the inner moisture barrier 110 in the base 102.
30 When the cavity 103a has been emptied, the inner heat seal 106 for that
cavity
becomes the outer heat seal 105 for cavity 103b thereby ensuring that the
empty
cavity 103b is not a source for moisture ingress.
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Figure 7 depicts a preferred construction for the dosing elPment 101 which
comprises two cooperating annular rings 111 a and 111 b which sit one above
the
other within a containing tray 112. The spacing between the annular rings 111
a and
111 b forms channels 107.
This arrangement allows each cavity to be spaced from an adjacent cavity by
as little as 1mm. In this way, 60 cavities can be arranged on a dosing disc
101 with a
diameter of 72mm. A desiccant 108 (not shown) to dry the air in the channels
107
between components 111 a, 111 b and 112 sits on the underside of annular ring
111 b
(see Figures 8 and 9) in a groove 113. A lid 104 would be heat sealed to the
io arrangement shown in Figure 7.
The annular ring 111 a has a plurality of cavities 114 and the annular ring
111 b
has a plurality of cavities 115.
With this arrangement, it is not necessary to injection mould the annular
rings
such that there are separate channels as in Figure 5. It is sufficient to
injection mould
1s the drug cavities 114 and 115 in the annular rings and sit the annular
rings one
above the other within the containing tray 112. The groove 113 for the
desiccant is
located on the underside of annular ring 111 b as viewed in Figure 7. The
spacing
between the annular rings 111 a and 111 b is sufficient for humidity
transport. Tooling
is considerably simpler and there is no need to form the narrow channels
depicted in
2o Figure 5. Spacing between the annular rings can be increased, for example,
by
increasing the roughness of the walls or applying a lattice pattem to the
walls.
