Dry powder inhaler with an outlet mesh

Abstract

The present invention provides a dry powder inhaler comprising: one or more doses of powdered medication; an outlet through which a user may inhale a dose of medication; an airway comprising a vortex chamber having a wall, an exit, a powder inlet channel, and optionally one or more bypass inlet channels, wherein the powder inlet channel and or the bypass inlet channels are tangential to the wall. A mesh is located at the exit of the vortex chamber. The mesh is formed from circumferential elements and radial elements which together define a plurality of openings. When a user inhales on the outlet, medication is entrained in an air flow and flows through the vortex chamber and the mesh in the airway and out through the outlet.

Description

[0001] Dry powder inhaler with an outlet mesh

[0002] Technical Field of the invention

[0003] The present invention relates to a dry powder inhaler for oral or nasal delivery of medication in powdered form, in particular an inhaler having a mesh in the outlet of the inhaler.

[0004] Background to the invention

[0005] Dry powder inhalers often have a mesh in the mouthpiece through which the aerosolized powder passes. The mesh can help to disperse the powder, as well as preventing any large fragments of e.g. a capsule or blister lid from entering the patient’s mouth. The mesh is typically in the form of a square or rectangular grid, for example as in WO2010 / 086285. However, since the outlet channel and / or mouthpiece is normally circular or elliptical in shape, a square or rectangular mesh results in small openings at the edge, where the circle / ellipse cuts across a mesh square. These small openings are liable to become blocked with powder, which reduces the amount of powder delivered to the patient and increases the air flow resistance (defined as the ratio of the square root of the differential pressure to the volumetric flow rate) of the inhaler. It would be desirable to have an inhaler which can deagglomerate powder effectively whilst also having a low air flow resistance.

[0006] Some inhalers (such as that disclosed in WO 2010 / 086285) have a vortex chamber (sometimes referred to as a “cyclone chamber”) for deagglomerating the powder. The vortex causes the drug-laden air flow to swirl and follow a generally helical path towards the mouthpiece. When the mesh is situated at the exit from a vortex chamber, it has an additional function, namely to “rectify” the vortexed air flow so that it is more laminar as it leaves the inhaler. This reduces the amount of powder that impacts on the patient’s mouth or throat. However, there is a need to balance rectification of the vortexed air flow (smaller openings in the mesh provide more rectification) and the air flow resistance of the mesh (small openings result in higher resistance). Brief Description of the invention

[0007] The present inventors have found that some or all of these drawbacks can be addressed by using a mesh that is formed by radial and circumferential elements, rather like a polar co-ordinate grid or a spider’s web. This avoids the problem of blockage caused by small openings. The absence of small openings also reduces the air flow resistance of the mesh itself.

[0008] Accordingly, the present invention provides a dry powder inhaler comprising:

[0009] • one or more doses of powdered medication comprising a pharmaceutically active ingredient;

[0010] • an outlet through which a user may inhale a dose of medication;

[0011] • an airway comprising a vortex chamber having a wall, an exit opening, a powder inlet channel, and optionally one or more bypass inlet channels, wherein the powder inlet channel and / or the bypass inlet channel(s) are tangential to the wall; and

[0012] • a mesh located at the exit of the vortex chamber, the mesh having a perimeter defined by the exit opening; wherein, when a user inhales on the outlet to create an air flow, medication is entrained in the air flow and flows through the airway, the vortex chamber and through the mesh, and out through the outlet; characterised in that the mesh is formed from circumferential elements and radial elements which together define a plurality of openings.

[0013] The vortex chamber has a powder inlet channel through which powder-containing air enters the vortex chamber. Thus the vortex chamber does not contain the medication until it has been aerosolized from its container (such as a blister) and has passed through the powder inlet channel. The vortex chamber may have one or more bypass inlet channels through which external, powder-free air enters the vortex chamber. The powder inlet channel and / or the bypass inlet channel(s) are tangential to the wall of the vortex chamber, so that the air flow(s) into the chamber create a vortex.

[0014] The inventors have found that the mesh of the invention can provide the same degree of rectification of the air flow as a square mesh but with a lower air flow resistance, so that the flow rate is higher (for a given pressure drop), which results in a higher fine particle dose. The size of the openings is chosen to provide a balance between rectification of the vortexed air flow (larger openings provide less rectification) and the air flow resistance of the mesh (small openings result in higher resistance).

[0015] A freely moving mixing element may be located inside the vortex chamber.

[0016] The circumferential elements may form one or more rings. The circumferential elements may be curved (when viewed perpendicular to the plane of the mesh), so that the rings may be for example circular or elliptical in shape. Alternatively, the circumferential elements may be straight so that they form polygons having five or more sides, preferably six, seven or eight sides.

[0017] The mesh may comprise a first ring of circumferential elements which surrounds a central opening. The mesh may comprise one, two, three, four or more further rings of circumferential elements, i.e. the mesh may have second, third, fourth, fifth rings etc..

[0018] The mesh may comprise five, six, seven, eight or more radial elements in the form of spokes which extend from the first ring that surrounds the central opening to the perimeter of the mesh. The mesh may comprise further radial elements that extend between adjacent rings and / or the perimeter of the mesh.

[0019] In a preferred embodiment, the mesh comprises first and second circular rings, seven radial elements that extend from the first ring to the perimeter of the mesh, and seven further radial elements that extend from the second ring to the perimeter of the mesh. In this embodiment, the mesh has a central circular opening surrounded by two annuli having seven and fourteen openings respectively, wherein all of the openings have approximately the same area.

[0020] In another preferred embodiment, the mesh comprises first, second and third circular rings, seven radial elements that extend from the first ring to the perimeter of the mesh, seven further radial elements that extend from the second ring to the third ring, and fourteen further radial elements that extend from the third ring to the perimeter of the mesh. In this embodiment, the mesh has a central circular opening surrounded by three annuli having seven, fourteen and twenty-one openings respectively, wherein all of the openings have approximately the same area. The spacing between the rings may vary. The spacing between the outermost ring and the perimeter of the mesh may be larger or smaller than the spacing(s) between the other rings.

[0021] The radial and / or circumferential elements may be of uniform thickness, so that they have a rectangular profile when viewed in the plane of the mesh (i.e. cross-section), or alternatively, they may be curved, for example with a generally elliptical profile at one or both ends. They may have a generally elliptical shaped cross-section at their upstream end (i.e. the end facing into the direction of the air flow) and a rectangular shape at their downstream end (i.e. the end facing into the mouthpiece).

[0022] The radial and / or circumferential elements may be arranged parallel to an axis of the outlet in the general direction of the air flow as it passes through the outlet and perpendicular to the plane of the mesh. Alternatively, the elements, in particular the radial elements, may be angled with respect to this axis, so that they are aligned more closely to the local direction of air flow, which includes a tangential component. The angle of the elements, in particular the radial elements, with respect to this axis may vary across the mesh, and in particular may increase towards the perimeter.

[0023] The radial and / or circumferential elements, in particular the radial elements, may be curved along their length (i.e. generally perpendicular to the plane of the mesh). The curvature of the elements, in particular the radial elements, may vary across the mesh, and in particular may increase towards the perimeter.

[0024] The length (i.e. generally perpendicular to the plane of the mesh) of the elements may vary across the mesh, and in particular may increase towards the perimeter.

[0025] The mesh may additionally comprise fins that extend downstream of the mesh into the outlet. The fins may be formed as extensions of some or all of the outermost radial elements (i.e. those adjacent to the perimeter of the mesh), or they may be formed as extensions from a shelf that surrounds the perimeter of the mesh.

[0026] Preferably the ratio of the diameter of the vortex chamber to the diameter of the exit (R) is given by 1.0 < R < 3.0, preferably 1.2 < R < 2.5. The inhaler may comprise a cover that holds and protects the inhaler. The cover may cover the outlet when the inhaler is located in the cover. The outlet may be exposed when the inhaler is removed from the cover. The outlet may be a mouthpiece or a nose piece.

[0027] The dose may be contained in a blister comprising a base and a lid, and the inhaler may comprise a piercer for piercing the lid of the blister. The inhaler may comprise a first housing part comprising the outlet and the piercer, and a second housing part comprising the blister, wherein the first and second housing parts are movable relative to each other. The first and second housing parts may be pushed together as the inhaler is removed from the cover, causing the piercer to pierce the lid of the blister.

[0028] Alternatively, the dose may be contained in a capsule and the opening mechanism may comprise a pair of needles for piercing the capsule.

[0029] The dose of the powdered medication may be 5-300 mg, preferably 20-200 mg, more preferably 30-150 mg, even more preferably 40-100 mg.

[0030] The pharmaceutically active ingredient may comprise a non-steroidal anti-inflammatory drug (NSAID), preferably, a salicylate, most preferably acetylsalicylic acid or a pharmaceutically acceptable salt thereof. Alternatively, the pharmaceutically active ingredient may comprise a bronchodilator; adrenaline and / or atropine; glucose and / or glucagon; benzodiazepine, phenytoin or anti-seizure medications; dihydroergotamine; naloxone; insulin; or a vaccine.

[0031] Brief Description of the Figures

[0032] Figure 1 shows an inhaler according to the invention.

[0033] Figure 2 shows the inhaler removed from the cover.

[0034] Figure 3 A is an expanded view showing the components of the inhaler.

[0035] Figure 3B shows a cross-section through the inhaler.

[0036] Figure 4 shows the central part of the inhaler from above.

[0037] Figure 5 shows a typical prior art mesh.

[0038] Figure 6A shows a mouthpiece with a mesh according to the invention.

[0039] Figure 6B is shows a mesh according to the invention in more detail.

[0040] Figure 7 shows a cross-section through an element of the mesh of Figure 6B. Figure 8 shows a second embodiment of a mesh.

[0041] Figure 9 shows a third embodiment of a mesh.

[0042] Figure 10 shows a cross-section through an element of a fourth embodiment of a mesh.

[0043] Figure 11 shows a fifth embodiment of a mesh.

[0044] Figure 12 is a view into the mouthpiece showing a sixth embodiment of a mesh.

[0045] Figure 13 is a view into the mouthpiece showing a seventh embodiment of a mesh.

[0046] Detailed Description of the invention

[0047] Figure 1 shows an inhaler according to the invention. The inhaler 1 has a housing 3 and a mouthpiece 4. A cover 2 holds and protects the inhaler. In particular, the cover has an extension 7 that extends over the mouthpiece 4, thereby preventing foreign material from entering the mouthpiece before use. The inhaler has a pair of grips 5 located on either side of the housing, and the cover has a pair of grips 6, for removing the inhaler from the cover.

[0048] To prepare the inhaler for use, the user holds the grips 5 of the inhaler 1 between the finger and thumb of one hand, and the grips 6 on the cover 2 between the finger and thumb of their other hand. The inhaler 1 is pulled out of the cover which uncovers the mouthpiece as shown in Figure 2. This action also causes a blister containing the medication to be pierced, thereby avoiding the need for any further user steps (such as pressing a button or lever to cause piercing) before use. The user then inhales on the mouthpiece to receive the medication.

[0049] Figure 3 A is an expanded view of the components of the inhaler 1. Figure 3B shows a crosssection through the inhaler. The inhaler has an upper housing part 10 with the mouthpiece 4, a central part 30, a mixing element 35, a blister 40 and a lower housing part 20. The central part 30 has two pairs of piercing elements 31 (for example of the type described in WO 2014 / 114916) on its lower surface.

[0050] The central part 30 is fixed (e.g. clipped or welded) in the upper housing part 10 so that the internal surface of the upper housing part and the upper surface of the central part together define an airway that fluidically connects the blister (once it has been pierced) to the mouthpiece 4 via a passage 32 and a vortex chamber 33. The mixing element 35 is located inside the vortex chamber 33. An exit opening with a mesh 12 is formed in the upper housing part; this connects the vortex chamber 33 to the mouthpiece 4. The blister 40 has a lid 41 and a base 42 with a rim 43 which fits into slots 21 on either side of the lower housing part 20, thereby holding the blister in place in the lower housing part.

[0051] The upper 10 and lower 20 housing parts are movable relative to each other. When the inhaler is in the cover 2, the upper and lower housing parts are held in an initial position in which the piercing elements 31 are held spaced apart from the lid 41 of the blister 40. The cover prevents the upper and lower housing parts from accidentally being pushed together before use. When the inhaler is removed from the cover, the cover interacts with the upper and lower housing parts, so that they are pushed together into an actuated position, in which the piercing elements 31 pierce the lid 41 and enter the blister 40. The mechanism for this consists of a pair of cams 8 in the form of pegs on the inside of the cover and two sloping cam surfaces 22, one in each side of the lower housing part 20. As the inhaler 1 is removed from the cover 2, the cams 8 slide along the cam surfaces 22, pushing the lower housing part 20 upwards into the upper housing part 10. One pair of piercing elements 31 creates an air entry opening in the lid 41 of the blister 40, and the other pair creates an exit opening.

[0052] Once the inhaler has been removed from the cover, the user inhales on the mouthpiece 4. This creates an air flow into the blister through the entry opening which aerosolizes the powder, and then carries it out through the exit opening into the passage 32 and then into the vortex chamber 33.

[0053] The central part 30 is shown from above in Figure 4. The powder-containing air flows from the passage 32 through a powder inlet channel 36 into the vortex chamber 33. External (i.e. powder-free) air also enters the vortex chamber through two bypass inlet channels 37, 38. The powder inlet channel 36 and the bypass inlet channels 37, 38 are tangential to the wall of the vortex chamber, so that the air flow into the chamber creates a vortex. This, in combination with the mixing element 35 (not shown in Figure 4) which is freely movable within the vortex chamber, breaks the powder up into fine particles. The diameter of the mixing element is larger than the width of the powder inlet channel 36 and the bypass inlet channels 37, 38 at the points where they enter the vortex chamber, so that the mixing element cannot enter the inlet channels.

[0054] The smallest particles tend to be in the centre of the vortex, whereas larger particles are closer to the edge. As a result, if the vortex chamber has a small exit opening, then only the very fine particles are able to pass out though the exit. However, a small exit opening also increases the air flow resistance, and hence decreases the flow rate through the inhaler. The optimal size for the exit opening is a compromise between these two effects. The size of the vortex chamber is limited by the need to keep the overall size of the inhaler reasonably small. The diameter of the vortex chamber may be from 10mm to 40mm, such as 12mm to 30mm, for example from 15mm to 20mm. The diameter of the exit of the vortex chamber may be from 5mm to 15mm, such as 7mm to 12mm, for example 8mm to 10mm. Preferably the ratio of the diameter of the vortex chamber to the diameter of the exit (R) is given by 1.0 < R < 3.0, preferably 1.2 < R < 2.5. In one embodiment, R is given by 1.5 < R < 2.0, more preferably 1.6 < R < 1.9. In another embodiment, R is given by 2.0 < R < 2.5, more preferably 2.1 < R < 2.3.

[0055] The aerosolized fine powder then then leaves the vortex chamber 33 via the mesh and flows out through the mouthpiece to the user’s lungs. The mesh prevents any large lumps of powder from leaving the vortex chamber.

[0056] The term “mesh” refers to a structure having a plurality of openings which are substantially larger (typically ~lmm in size) than aerosolized powder particles (typically <5 pm). The mesh is therefore not a filter for aerosolized particles. Meshes in the form of square or rectangular grids are known for helping to deagglomerate powder and / or for preventing large particles from exiting the inhaler, as disclosed for example in W02005 / 037353. Figure 5 shows a square mesh 100, as disclosed in WO 2010 / 086285. The outlet 101 within which the mesh is located is circular in shape. Consequently, the square mesh results in partial openings 102 at the edge, where the circular perimeter cuts across a mesh square. These partial openings are liable to become blocked with powder, which reduces the amount of powder delivered to the patient and increases the air flow resistance of the inhaler. The present inventors have found that a mesh having a specific design overcomes this problem and performs particularly well.

[0057] Figure 6A is a perspective view showing a mesh 12 according to the invention inside the mouthpiece 4. Figure 6B shows the mesh in more detail. The mesh is formed by radial and circumferential elements. The spacing between the radial and circumferential elements was selected so that all the openings have approximately the same area. The absence of partial openings at the edge of the mesh avoids the problem of powder blockage. The mesh 12 comprises three circular rings of circumferential elements 50, 51, 52, and seven radial elements which form spokes 60 that extend from the central (first) ring 50 to the perimeter 55 of the mesh. There are also further radial elements 61, 62 between the second 51 and third 52 rings, and between the third ring 52 and the perimeter 55 respectively. The annulus between the first 50 and second 51 rings is divided into seven openings by the spokes 60. The openings between the second 51 and third 52 rings are defined by the spokes 60 together with the seven radial elements 61. The radial elements 61 are spaced equiangularly between the spokes, so that each gap between the spokes is divided into two equal openings. The openings between the third ring 52 and the perimeter 55 are defined by the spokes 60 and by the seven pairs of radial elements 62. The radial elements 62 are spaced equiangularly between the spokes, so that each gap between spokes is divided into three equal openings. Thus, the mesh has a central circular opening 70 defined by the first ring, surrounded by three annuli having seven, fourteen and twenty-one openings 71 respectively, which take the form of annular sectors.

[0058] In the mesh shown in Figure 6B, the spacing between the third ring 52 and the perimeter is larger than the spacing between the first 50 and second 51 rings, and the spacing between the second 51 and third 52 rings. Consequently, the twenty-one openings in the outer annulus are larger than the openings in the middle and inner annuli; this reduces the possibility of the openings in the outer annulus becoming blocked. However, the spacing of the radial and / or circumferential elements may be chosen so that all of the openings are (approximately) the same size, or they may vary (e.g. as a function of radius) in other ways. The central aperture within the first ring 50 suitably has a diameter of from 0.5 to 1.5mm, preferably from 0.7 to 1.2mm, more preferably 0.8 to 1mm, such as about 0.85mm. The spacings between the first 50 and second 51 rings, between the second 51 and third 52 rings and between the third ring 52 and the perimeter 55 are each suitably from 0.5 to 1.5mm, preferably from 0.7 to 1.3mm, more preferably 0.8 to 1.2 mm, such as about 1mm.

[0059] The numbers of circumferential elements and radial elements are not limited to those of the mesh of Figure 6B. For example, there may be 1, 2, 3, 4, 5 or more rings of circumferential elements; and from 5 to 10 spokes, for example 6, 7 or 8 spokes. There may be 1, 2, 3, 4 or more radial elements between each pair of spokes. The circumferential elements may form a circular ring, as shown in Figure 6B. However, in some inhalers the mouthpiece and / or flow channel in which the mesh is situated has a non-circular shape, such as an ellipse with an eccentricity of greater than 0. In such inhalers, the mesh suitably has circumferential elements that form elliptical rings with the same eccentricity as the opening. Thus, each of the embodiments described above could have circumferential elements that form (non-circular) elliptical rings.

[0060] Moreover, the circumferential elements could be straight rather than curved, so that they form polygonal rings rather than circular rings. The polygonal rings may have five, six, seven, eight or more sides (i.e. the rings may be pentagonal, hexagonal, heptagonal, octagonal etc.) However, meshes formed with fewer than five spokes and with polygonal rings having fewer than five sides are not suitable because these shapes result in small openings at the edge, where a circular or elliptical perimeter cuts across a mesh opening. If the channel in which the mesh is situated has a non-circular elliptical shape, then the polygonal rings are not regular polygons, but preferably have a similar eccentricity to the shape of the channel.

[0061] The spacing between the circumferential elements is typically between 0.5mm and 2mm, such as from 0.7mm to 1.2mm. The diameter of the central opening may be similar to the spacing between the circumferential elements, for example between 0.5mm and 2mm.

[0062] This form of mesh has been found to have a number of advantages, including very effective deagglomeration of the powder, as measured by the fine particle dose, i.e. the mass of particles below a certain size, such as 5pm, that is delivered from the inhaler, known as the FPD.

[0063] The elements may be of uniform thickness, so that they are rectangular in cross-section. However, the elements are preferably in the form of an elongated ellipse with the long axis parallel to the axis of the mouthpiece and the general direction of air flow (i.e. perpendicular to the plane of the mesh), as shown in Figure 7. Elements that are elliptical in profile reduce the air flow resistance of the mesh. The elements may have an elliptical shaped cross-section at their upstream end (i.e. the end facing into the direction of the air flow) and a rectangular shape at their downstream end (i.e. the end facing into the mouthpiece). This results in a bulletlike shape which presents an aerodynamic profile at the upstream end. The elements are suitably from 0.3 to 0.7mm in width at their widest point, such as about 0.5mm. The length of the elements is suitably from 1 to 3mm, such as from 1.5 to 2.5mm, for example about 2mm. The central opening is particularly important because the smallest particles are found near the centre of the vortex. Thus, if the centre were solid or if the spokes 60 continued inside the first circular ring 50 to the centre of the mesh, or if the diameter of the central opening were very small, these very fine particles could be prevented from exiting the vortex chamber.

[0064] For this reason, the diameter of the central opening may alternatively be larger than the spacing between the circumferential elements, for example between 1mm and 6mm, such as from 2mm to 5mm, or from 3mm to 4mm. The tangential velocity of the airflow at the centre of the vortex is relatively low, so relatively little rectification is required in this region. For example, the mesh shown in Figure 6B could be modified by removing the first circular ring 50 and arranging the spokes 60 so that they extend only outwards from the second circular ring 51 to the perimeter 55.

[0065] In the mesh shown in Figure 8, the openings are smaller at the edge than at the centre. This provides greater rectification near the edge of the mesh, where the tangential velocity of the air flow is highest. Of course, the openings near the edge must still be sufficiently large to avoid being blocked by powder.

[0066] A convenient way of creating smaller openings at the edge of the mesh is to have a number (such as three) of evenly spaced circular rings, and a number (such as six, seven or eight) of equiangularly spaced spokes, but to have an increased number of additional radial elements in the outer annulus. The circumferential size of the openings is expected to have a greater effect on rectification than the radial size of the openings, because it is the radial elements, rather than the circumferential ones, that cause the change in direction of the air flow.

[0067] Instead of being aligned parallel to the axis of the mouthpiece as shown in Figure 7, the elements, in particular the radial elements, may be angled with respect to this axis, as illustrated in Figure 9. This has the effect that the elements are aligned more closely to the local direction of air flow, which includes a tangential component (clockwise in Figure 9) as well as along the axis of the mouthpiece. This reduces the air flow resistance of the mesh and results in a more gradual rectification of the vortexed air flow. Without wishing to be limited by theory, it is believed that having angled elements has the effect that the openings are less likely to become blocked with powder, since the angle at which powder particles impact the surface of the elements is reduced. Moreover, the formation of stagnant regions behind the elements where powder can accumulate is avoided. The angle of the elements with respect to the axis of the mouthpiece is preferably larger near the edge of the mesh, where the tangential velocity of the air flow is highest.

[0068] Instead of being tilted, so that the angle between the element and the mouthpiece axis is essentially constant, the elements, in particular the radial elements, may be curved so that the angle changes along the length of the element. For example, the angle may decrease in the direction of air flow, so that the upstream (vortex chamber) end of the element is at a greater angle than the downstream (mouthpiece) end, which may be parallel, or nearly parallel to the axis of the mouthpiece. In this way, the elements can be shaped, for example rather like a turbine blade, as shown in Figure 10. This results in a more gradual change in direction of the air flow as it passes through the mesh, which is expected to produce very good rectification while reducing the deposition of powder on the mesh. The curvature of the elements is preferably larger near the edge of the mesh, where the velocity of the air flow in the tangential direction is greatest.

[0069] The length of the elements (whether parallel to the axis of the mouthpiece, angled or curved) may be the same across the whole mesh. However, in another embodiment shown in Figure 11, the elements in the outer ring are longer than those in the middle ring, which are in turn longer than those in the inner ring. The longer the element, the greater the amount of rectification of the vortexed air flow. Thus, in this embodiment, there is greater rectification at the edge of the mesh where the velocity of the air flow in the tangential direction is greatest. The elements are shorter in the centre of the mesh where there is less need for rectification. Having longer elements in the centre would not provide any significant benefit in terms of rectification, but would increase the air flow resistance of the mesh to some extent. In Figure 11, the elements are curved as shown in Figure 10, and hence, when viewed directly from above, the openings appear to be partially occluded. However, the elements could equally be parallel to the axis of the mouthpiece as in Figure 7 or angled as in Figure 9. The mesh may consequently have a stepped profile when viewed from the side (i.e. in the plane of the mesh), so that the thickness of the mess decreases in steps at each ring from the perimeter to the centre. The angle and / or curvature and / or length of the elements, in particular the radial elements, may be constant within a ring but increase in a stepwise manner from the ring closest to the centre to the ring closest to the perimeter.

[0070] In yet another embodiment shown in Figure 12, the mesh may have fins 80 formed as extensions of some of the outermost radial mesh elements that extend into the mouthpiece, i.e. in the downstream direction. The fins provide further rectification of the air flow without significantly increasing the air flow resistance.

[0071] Figure 13 shows a variation of the embodiment of Figure 12. In this embodiment, the mesh is surrounded by a shelf 90 so that the mesh does not occupy the whole of the cross-section of the mouthpiece. The shelf may be flat (i.e. planar) and may have a thickness that corresponds to the length of the elements of the mesh. Alternatively, the shelf could be shaped so that the downstream (i.e. mouthpiece) side is sloped or curved to provide a gradual transition from the edge of the mesh to the inside surface of the mouthpiece, as is shown in Figure 13. The fins 80 may extend from the shelf 90 into the mouthpiece, i.e. in the downstream direction. As before, the fins help to rectify the air flow without significantly increasing the air flow resistance. In another variant, the shelf is present but without any fins.

[0072] The inhaler described above has a blister that contains the dry powder medication, which is pierced by the piercing elements. However, the invention also encompasses other containers, such as a capsule, and other opening mechanisms, such as peeling a lid off, pulling two halves of a capsule apart or piercing a capsule by means of needles. Regardless of which type of opening mechanism is used, the inhaler may be automatically actuated by the action of removing it from the cover.

[0073] The inhaler may have a single dose of medication, and may be pre-loaded with a blister or capsule. The inhaler may be re-usable, so that a new blister or capsule in inserted each time it is to be used. Alternatively, the inhaler may be a multi-dose device and contain a number of doses, for example 30 or 60 doses in a blister strip, dose disk or a reservoir, along with a suitable mechanism for preparing each dose.

[0074] The blister, capsule or other container contains a dry powder medication for inhalation. The medication comprises a pharmaceutically active ingredient and may also comprise one or more pharmaceutically acceptable excipients. The amount of the powdered medication in the blister or capsule may be 5-300 mg, preferably 20-200 mg, more preferably 30-150 mg, even more preferably 40-100 mg. For example, there may be about 50, 60, 70, 80 or 90 mg of powder in the blister or capsule. The contents of each inhaler may be delivered from the inhaler in a single inhalation or in two or more inhalations.

[0075] The medication may be capable of treating or preventing a thromboembolic event. The pharmaceutically active ingredient in the medication may be an antiplatelet drug. For example, the pharmaceutically active ingredient may be a non-steroidal anti-inflammatory drug (NSAID). Preferably, the pharmaceutically active ingredient is a salicylate (a salt or ester of salicylic acid), most preferably acetylsalicylic acid or a pharmaceutically acceptable salt thereof. The pharmaceutically active ingredient may be another type of NSAID. For example, the pharmaceutically active ingredient may be Celecoxib (Celebrex), Dexdetoprofen (Keral), Diclofenac (Voltaren, Cataflam, Voltaren-XR), Diflunisal (Dolobid), Etodolac (Lodine, Lodine XL), Etoricoxib (Algix), Fenoprofen (Fenopron, Nalfron), Firocoxib (Equioxx, Previcox), Flurbiprofen (Urbifen, Ansaid, Flurwood, Proben), Ibuprofen (Advil, Brufen, Motrin, Nurofen, Medipren, Nuprin), Indomethacin (Indocin, Indocin SR, Indocin IV), Ketoprofen (Actron, Orudis, Oruvail, Ketoflam), Ketorolac (Toradol, Sprix, Toradol IV / IM, Toradol IM), Licofelone (under development), Lorn oxicam (Xefo), Loxoprofen (Loxonin, Loxomac, O%er|o), Lumiracoxib (Prexige), Meclofenamic acid (Meclomen), Mefenamic acid (Ponstel), Meloxicam (Movalis, Mel ox, Recoxa, Mobic), Nabumetone (Relafen), Naproxen (Aleve, Anaprox, Midol Extended Relief, Naprosyn, Naprelan), Nimesulide (Sulide, Nimalox, Mesulid), Oxaporozin (Daypro, Dayrun, Duraprox), Parecoxib (Dynastat), Piroxicam (Feldene), Rofecoxib (Vioxx, Ceoxx, Ceeoxx), Salsalate (Mono-Gesic, Salflex, Disalcid, Salsitab), Sulindac (Clinoril), Tenoxicam (Mobi flex), Tolfenamic acid (Clotam Rapid, Tufnil), or Valdecoxib (Bextra). The pharmaceutically active ingredient may be an alternative to an NSAID. Such alternatives include P2Y12 inhibitors. Examples of P2Y12 inhibitors include Plavix (clopidogrel), ticlopidine, ticagrelor, prasugrel, and cangrelor. Other pharmaceutically active ingredients may include COX-2 inhibitors, and Nattokinase (an enzyme (EC 3.4.21.62, extracted and purified from a Japanese food called natto). The medication may comprise both acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, and a P2Y12 inhibitor.

[0076] The pharmaceutically active ingredient may alternatively be a bronchodilator, such as a beta-2 agonist or anticholinergic for the treatment of an asthma exacerbation; adrenaline and / or atropine for the treatment of cardiac failure, cardiac dysfunction, cardiac arrest, anaphylaxis, drug overdose or the like; glucose and / or glucagon for the treatment of hypoglycaemia, diabetes induced coma or the like; benzodiazepine, phenytoin or anti-seizure medications for the treatment of seizure; dihydroergotamine for the treatment of migraine; naloxone for treating an opioid overdose; insulin for managing blood sugar level or the like.

[0077] The medication may include one or more agents for inducing an immune response, e.g. a vaccine, such as a measles vaccine, a Hepatitis B vaccine, or an influenza vaccine.

[0078] The term “pharmaceutically active ingredient” does not include nicotine or nicotine salts. Thus the medication does not contain nicotine or nicotine salts.

[0079] Example

[0080] The performance of an inhaler with a mesh according to the invention was compared with that of an inhaler with a conventional square mesh. The mesh according to the invention was similar to that shown in Figures 6A and 6B, except that spacing between each of the rings, and between the third ring and the perimeter, was equal (0.95mm) so that the area of all of the openings were equal. The square mesh was similar to the mesh shown in Figure 5. The spacing between the ribs (0.87mm) was chosen so that the area of the square openings was the same as the area of the openings in the mesh according to the invention, so that the air flow resistances of the meshes were approximately equal (the resistance of the square mesh was slightly higher than that of the mesh according to the invention). Both meshes were 2mm long (i.e. in the direction of air flow). The ribs were shaped as shown in Figure 7, and were 0.55mm thick in the centre.

[0081] Apart from the meshes, the inhalers were identical, and as shown in Figures 1 to 4. The vortex chamber was 17.5 mm in diameter and had a circular exit opening to the mouthpiece 10mm in diameter. The vortex chamber contained a mixing element in the form of three orthogonal circular discs with diameter of 6mm and a common centre, as shown in Figures 3 A and 3B and described in our co-pending application EP24180895.

[0082] Blisters were filled with 85mg of a powder consisting of micronized acetylsalicylic acid powder (99.5% ASA) and magnesium stearate (0.5% MgSt). A Fast Screening Impactor (FSI, Copley Scientific) was used to measure the fine particle dose (< 5pm) delivered from each inhaler. The FSI has a filter which captures emitted aerosol particles of less than 5pm in size. Simulated inhalation manouevres were performed on each inhaler at three different pressure drops of IkPa, 2kPa and 4kPa. The manoeuvres consisted of two inhalations, each with a volume of 2 litres The FPD was determined gravimetrically by weighing the filter before and after each inhalation manouevre. The results are shown in Table 1.

[0083] Table 1 : FSI results

[0084] Table 1 demonstrates that the mesh according to the invention resulted in a higher FPD than the square mesh at IkPa and 2kPa, and a similar FPD (within experimental error) at 4kPa. Moreover, the FPD was less dependent on the flow rate for the mesh according to the invention. A lower dependency of the FPD on the flow rate is advantageous because different patients may inhale at very different flow rates, and hence could receive very different doses.

Claims

Claims1. A dry powder inhaler comprising:• one or more doses of powdered medication comprising a pharmaceutically active ingredient;• an outlet through which a user may inhale the medication;• an airway comprising a vortex chamber having a wall, an exit, a powder inlet channel, and optionally one or more bypass inlet channels, wherein the powder inlet channel and / or the bypass inlet channels are tangential to the wall; and• a mesh located at the exit of the vortex chamber, the mesh having a perimeter; wherein, when a user inhales on the outlet, medication is entrained in an air flow and flows through the vortex chamber and the mesh, and out through the outlet; characterised in that the mesh is formed from circumferential elements and radial elements, which together define a plurality of openings.

2. A dry powder inhaler according to claim 1, wherein the circumferential elements form one or more rings that are circular, elliptical, or polygonal with five or more sides.

3. A dry powder inhaler according to claim 2, wherein a first ring of the one or more rings surrounds a central opening.

4. A dry powder inhaler according to claim 3, wherein the mesh comprises five or more radial elements that extend from the first ring to the perimeter of the mesh.

5. A dry powder inhaler according to claim 4, wherein the mesh comprises a second ring, and further radial elements that extend between the second ring and the perimeter of the mesh.

6. A dry powder inhaler according to claim 4, wherein the mesh comprises a second ring and a third ring, and further radial elements that extend between the second ring and the third ring, and between the third ring and the perimeter of the mesh.

7. A dry powder inhaler according to claim 6, wherein the rings are circular, and wherein the mesh comprises seven radial elements that extend from the first ring to the perimeterof the mesh, seven further radial elements that extend from the second ring to the third ring, and fourteen further radial elements that extend from the third ring to the perimeter of the mesh.

8. A dry powder inhaler according to claim 7, wherein the spacing between the third ring and the perimeter of the mesh is larger than the spacings between the first and second, and second and third rings.

9. A dry powder inhaler according to any of claims 1 to 8, wherein the radial and / or circumferential elements are generally elliptical in cross-section, or are elliptical in crosssection at an upstream end.

10. A dry powder inhaler according to any of claims 1 to 9, wherein the elements are parallel to an axis of the outlet in the general direction of the air flow.

11. A dry powder inhaler according to any of claims 1 to 9, wherein the elements are angled or curved with respect to an axis of the outlet in the general direction of the air flow as it passes through the outlet.

12. A dry powder inhaler according to any of claims 1 to 11, wherein the ratio of the diameter of the vortex chamber to the diameter of the vortex chamber exit (R) is given by 1.0 < R < 3.0, preferably 1.2 < R < 2.5.

13. A dry powder inhaler according to any of claims 1 to 12 wherein the dose of powdered medication is contained in a blister comprising a base and a lid, and the inhaler comprises a piercer for piercing the lid of the blister.

14. A dry powder inhaler according to any of claims 1 to 13, wherein the medication comprises a non-steroidal anti-inflammatory drug; a bronchodilator; adrenaline and / or atropine; glucose and / or glucagon; benzodiazepine, phenytoin or anti-seizure medications; dihydroergotamine; naloxone; insulin; or a vaccine.

15. A dry powder inhaler according to any of claims 1 to 14, wherein each dose is from 5 to 300mg of powdered medication.

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