Preferred embodiments of the present invention will now be described in detail, by way of example only, with reference to the accompanying drawings, of which:
FIG. 1 is a graphic representation of the relative humidity gradient across a barrier for a drug with conventional moisture protection;
FIG. 2 is a graphic representation of the relative humidity gradient across a barrier arrangement with moisture protection according to the present invention;
FIG. 3 is a section through one blister in a blister pack with moisture protection according to a preferred embodiment of the present invention;
FIGS. 4A, 4B and 4C depict preferred embodiments of blister packs with multiple cavities having moisture protection;
FIG. 5 is a plan view of a section of a dosing element for an inhalation device having moisture protection according to a preferred embodiment of the present invention;
FIG. 6 is a sectional view in direction X-X through the dosing element in FIG. 5;
FIG. 7 depicts a further preferred embodiment of a dosing element having moisture protection;
FIG. 8 depicts the underside of annular ring 111b in FIG. 7; and,
FIG. 9 is an enlarged view of part of the annular ring in FIG. 8.
Reference should now be made to FIG. 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 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 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. FIG. 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 moisture diffusion as in FIG. 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.
FIG. 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 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 FIG. 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 approximately 20% then there will only be minimal moisture diffusion through the heat seal 6 to the cavity 3 assuming that the relative humidity within cavity 3 is also approximately 20%.
Reference should now be made to FIGS. 4A, 4B and 4C which depict three configurations for a blister pack having a plurality of cavities 3. In FIG. 4A each 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. FIG. 4B depicts a further modification using a rectangular channel configuration. FIG. 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 FIG. 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. FIG. 5 shows a segment of the annular dosing element 101 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. FIG. 6 is a sectional view taken in direction X-X through the dosing element in FIG. 5.
The base 102 of the dosing element 101 would typically be injection moulded 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 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.
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.
FIG. 7 depicts a preferred construction for the dosing element 101 which comprises two cooperating annular rings 111a and 111b which sit one above the other within a containing tray 112. The spacing between the annular rings 111a and 111b forms channels 107.
This arrangement allows each cavity to be spaced from an adjacent cavity by as little as 1 mm. In this way, 60 cavities can be arranged on a dosing disc 101 with a diameter of 72 mm. A desiccant 108 (not shown) to dry the air in the channels 107 between components 111a, 111b and 112 sits on the underside of annular ring 111b (see FIGS. 8 and 9) in a groove 113. A lid 104 would be heat sealed to the arrangement shown in FIG. 7.
The annular ring 111a has a plurality of cavities 114 and the annular ring 111b 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 FIG. 5. It is sufficient to injection mould 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 111b as viewed in FIG. 7. The spacing between the annular rings 111a and 111b is sufficient for humidity transport. Tooling is considerably simpler and there is no need to form the narrow channels depicted in FIG. 5. Spacing between the annular rings can be increased, for example, by increasing the roughness of the walls or applying a lattice pattern to the walls.
Patent Application
20080023367
