Inhaler apparatus

Abstract

There is provided an inhaler apparatus for aerosolising a powdered medicament contained within a circular blister. The apparatus comprises a plate for engaging a circular blister. The plate comprising an air-outlet piercer for piercing an air outlet through a seal of the blister. The air-outlet piercer is axially positioned in the blister. The plate further comprises a plurality of air-inlet piercers surrounding the air-outlet piercer, each for piercing an inlet opening through the seal. Each air-inlet piercer comprises an air-inlet opening. Each air-inlet piercer comprises a side wall substantially perpendicular to the plate. Each air-inlet piercer comprises a foil deflecting wall. A first side of the foil deflecting wall and the side wall meet to form a cutting edge.

Description

[0001] Inhaler apparatus

[0002] Technical Field

[0003] The present disclosure relates to an inhaler apparatus for aerosolising a powdered medicament contained within a circular blister. The powdered medicament may comprise an active pharmaceutical ingredient (API) or an active pharmaceutical ingredient (API) and a carrier.

[0004] The present disclosure also relates to a drug delivery device for aerosolising a powdered medicament contained within a circular blister. The powdered medicament may comprise an active pharmaceutical ingredient (API) or an active pharmaceutical ingredient (API) and a carrier.

[0005] Background of Disclosure

[0006] A dry powdered medicament for inhalation typically comprises an active pharmaceutical ingredient (API) in the form of a powder, the API may be mixed with a carrier powder such as lactose powder. The particle size of the API powder is very small, much smaller than the particle size of the carrier, and the total mass of API in a dose is typically very small. During processing, therefore, the very small mass of API is often blended with a much larger mass of the carrier powder. The API particles adhere to the carrier particles so that the combined medicament is easier to handle during packaging.

[0007] However, if a dose of this medicament is administered using a conventional inhaler, a problem arises because the API remains adhered to the carrier particles and both the API and carrier particles are inhaled. The carrier particles are inert and so their inhalation causes no health problem, but the larger mass of the carrier particles prevents them from following the inhaled air-flow into a user’s lungs where the API is intended to be delivered. The carrier particles with the API adhering to them are too massive to be carried effectively by the inhaled air-flow around corners in the user’s throat (particularly at the back of the mouth where the airflow turns from the user’s mouth into the user’s windpipe). The particles of the medicament therefore tend to deposit in the user’s throat and mouth before they reach their intended target in the lungs.

[0008] One solution to this problem may be not to combine the API with carrier particles. In that case, the user can inhale only the smaller API particles, and these smaller particles may be carried more effectively by the user’s inhaled airflow and delivered directly the lungs. This may advantageously enhance the therapeutic effect of the API particles. There are a number of constraints in designing an inhaler with a powdered medicament comprising 100% API, including how to effectively aerosolise and evacuate all the API from the primary container, for example a blister.

[0009] An aim of the present disclosure is to provide an inhaler apparatus that addresses the problem of improving the dose of API delivered to the patient.

[0010] However, for ease of handling the small API particles during manufacture and packaging, it may be desirable to blend them with carrier particles. When carrier particles are used, to solve the problem of a user inhaling a dose of medicament while the API is still adhering to the carrier particles, it is desirable to deagglomerate the medicament before inhalation to separate the API from the carrier so that the API is inhaled by itself. The smaller API particles can then be more effectively carried by the inhaled air flow into the user’s lungs.

[0011] There are a number of constraints in designing an inhaler for deagglomerating an API powder from a carrier powder. Including the fact that a user inhaling through a drug-delivery device can only generate a limited amount of energy. Inhalers which use only the energy in the inhaled air-flow may be termed passive inhalers. In passive inhalers, the energy available to deagglomerate the medicament is limited. In other inhalers, termed active inhalers, an additional source of energy such as a pressurised gas may be used to improve deagglomeration, but only at the cost of a much more complex drug-delivery device.

[0012] The problem of deagglomerating an API from a carrier is becoming more acute because there is increasing interest in large-dose medicaments for inhalation, which require greater amounts of energy to deagglomerate than for smaller doses. This increased mass of medicament must be deagglomerated and delivered to the lungs of the user consistently, irrespective of the variable levels of inhalation energy provided by different patients. This makes the problem of deagglomerating or classifying the medicament to separate the API from the carrier even more difficult, particularly in a passive inhaler. In a passive inhaler, the increased mass of medicament must be deagglomerated using the same inhalation energy available from a user.

[0013] An aim of the disclosure is to provide an inhaler apparatus that addresses the problem of efficient deagglomeration, and to enable efficient and effective deagglomeration and classification even for larger dose sizes.

[0014] Another aspect of the provision of dry-powder medicaments is the packaging of the medicaments. One simple and effective packaging method is blister packaging, in which a medicament is stored in a blister pocket sealed by a rupturable blister seal or lid, such as a blister foil. In the prior art, inhalers have been developed to allow inhalation of medicaments stored in blisters. Typically, in such an inhaler the lid of a blister may be pierced by a portion of an inhaler device and the entire dose of medicament removed from the blister for inhalation.

[0015] However, when the lid or seal of a blister is pierced by a portion of the inhaler device, the cut portions of the lid or seal are pushed into the blister. In many prior art piercer designs, these cut portions of the seal may occlude the air inlet and as such interrupt or impede the air flow, or be deflected into the blister so that the cut flaps of seal interrupt the intended airflow pathway inside the blister. Further, in many prior art piercer designs, the manner in which the lid or seal are pierced or cut results in inconsistent and variable cut portions of the seal. This can in turn lead to inconsistent airflow.

[0016] Therefore, a further aim of the disclosure is to provide an inhaler apparatus that addresses the problem of how to provide uninterrupted air flow inside a pierced blister.

[0017] Summary of the Disclosure

[0018] Embodiments described herein provide an inhaler apparatus and a drug-delivery device for aerosolising a powdered medicament contained within a circular blister as defined in the appended independent claims, to which reference should now be made. Preferred or advantageous features of the disclosure are set out in the dependent claims.

[0019] The present disclosure relates to an inhaler apparatus for aerosolising a powdered medicament contained within a circular blister. The apparatus may comprise a plate for engaging a circular blister. The plate may comprise an air-outlet piercer for piercing an air outlet through a seal of the blister. The air-outlet piercer may be axially positioned in the blister, in use. The plate may further comprise a plurality of air-inlet piercers surrounding the air-outlet piercer, each for piercing an inlet opening through the seal. Each air-inlet piercer may comprise an air-inlet opening. Each air-inlet piercer may comprise a side wall substantially perpendicular to the plate. Each air-inlet piercer may comprise a foil deflecting wall. A first side of the foil deflecting wall and the side wall may meet to form a cutting edge.

[0020] First Aspect According to a first aspect of the present disclosure, there is provided an inhaler apparatus for aerosolising a powdered medicament contained within a circular blister. The apparatus comprises a plate for engaging a circular blister. The plate comprising an air-outlet piercer for piercing an air outlet through a seal of the blister. The air-outlet piercer is axially positioned in the blister, in use. The plate further comprises a plurality of air-inlet piercers surrounding the air-outlet piercer, each for piercing an inlet opening through the seal. Each air-inlet piercer comprises an air-inlet opening. Each air-inlet piercer comprises a side wall substantially perpendicular to the plate. Each air-inlet piercer comprises a foil deflecting wall. A first side of the foil deflecting wall and the side wall meet to form a cutting edge.

[0021] The powdered medicament may comprise an active pharmaceutical ingredient (API) only. In this manner, the powdered medicament may consist of API powder. In other words, the powdered medicament may comprise 100% API. Alternatively, the powdered medicament may comprise an API and a carrier. The API may be in the form of a powder, mixed with a carrier powder such as lactose powder. When the powdered medicament comprises an API mixed with a carrier the API may form up to 20% of the powdered medicament, preferably up to 15% of the powdered medicament. Alternatively, API and carrier powder may be filled into the blister without prior mixing, i.e. , the API and carrier may be filled separately into the same blister. The predominantly cyclonic flow regime within the blister, promoted by the inhaler apparatus according to the present disclosure, will mix the API and carrier during use. The present inventors have appreciated that it is advantageous to be able to have the API and carrier separate. This is because it allows for much higher ratios of API to carrier, for example, 50% API to 50% carrier, or even higher, for example, 75% API to 25% carrier. Effectively mixing the API and carrier during the inhalation overcomes the difficulty in achieving high strength blends prior to filling the blister, as it is difficult to achieve homogeneity, in other words, consistency in the mixture, with blends that typically contain greater than 15% API. This is particularly advantageous for low potency medicaments, that require much higher doses of API.

[0022] In combination, the inhaler apparatus and a blister containing the medicament form an apparatus for deagglomerating and aerosolising the medicament for inhalation, by separating (or classifying) the API from the carrier, when the powdered medicament comprises both an API and a carrier.

[0023] In combination, the inhaler apparatus and the blister containing the medicament form an apparatus for aerosolising the powdered medicament in the blister for inhalation, when the powdered medicament comprises 100% API. The blister contains the medicament, and comprises a circular blister pocket sealed by a pierceable or rupturable seal, such as a foil seal. The inhaler apparatus comprises; the airoutlet piercer for piercing the seal to form an air outlet, through which air can be drawn towards an inhaler mouthpiece for delivering a flow of aerosolised and / or deagglomerated medicament to a user; and two or more (preferably three, four or five) air-inlet piercers, each for piercing the seal to form an air inlet for directing air into the blister when air is drawn through the outlet. In a particularly advantageous example, the apparatus comprises four air-inlet piercers.

[0024] In use, the inhaler apparatus is initially engaged with the blister so that the piercers pierce the seal. When the piercers pierce the seal, the air outlet is advantageously axially positioned in the circular blister, and each inlet is positioned between the air outlet and an edge of the blister. When the inhaler apparatus is fully engaged with the blister, both the airoutlet piercer and the air-inlet piercers project or protrude through the seal into the interior of the blister.

[0025] When air is then drawn from the blister through the air outlet, in an air-outlet direction, the air inlets are positioned to direct airflow into the blister so that a circulating, or cyclonic, airflow is created within the blister. The cyclonic airflow advantageously carries the medicament circumferentially within the blister.

[0026] When the medicament comprises both the API and the carrier, the cyclonic airflow produced advantageously deagglomerates the API from the carrier as particles collide with each other and with walls of the blister.

[0027] When the medicament comprises API only, the cyclonic airflow produced advantageously evenly distributes the API particles within the blister for effective aerosolisation and evacuation.

[0028] The cyclonic airflow also advantageously accelerates the medicament away from the air outlet, so that only smaller, lighter particles in the medicament can be drawn through the air outlet. This is particularly advantageous when the powdered medicament is carrier based, the API particles being smaller and lighter than the carrier particles, and so the API is preferentially drawn through the outlet, classifying the medicament, for inhalation by a user. This advantageously increases the concentration of API in the emitted dose and as such increases the therapeutic efficacy of the device. Increasing the concentration of API in the emitted dose is particularly advantageous for the delivery of large doses. This is because it reduces the total mass of the emitted dose by reducing the relative mass of carrier particles emitted, and, thereby, reduces the risk of inducing coughing in the patient. Conventional dry powdered inhaler (DPI) technology, which does not classify and therefore emits all of the filled mass, delivers the formulation at the same concentration at which it was filled. The concentration of the delivered dose is therefore limited by what can be achieved in blending, which is typically up to about 15%. By classifying the carrier fraction within the blister, apparatus according to the present disclosure can typically achieve about a four-fold increase in the emitted concentration. This means four times the dose can be delivered for the same total emitted mass. This significantly reduces the chance of cough, in particular, with large doses.

[0029] According to the first aspect, each air-inlet piercer comprises a side wall which projects out of the plate so that the air-inlet piercer side wall is substantially perpendicular to the plate. This is different to prior art piercer designs, which typically comprise sloping walls that are not perpendicular to the plate. Each air-inlet piercer also comprises a foil deflecting wall for deflecting a portion of foil seal in use. A first side of the foil deflecting wall and the side wall meet to form a cutting edge for cutting through the seal of the blister.

[0030] The cutting edge is positioned along the “top” of the piercer side wall (the edge of the side wall furthest from the plate), so that when the piercers are urged, pushed or punctured through the seal and into the blister in use, the cutting edge is the edge of the air-inlet piercers that contact and cut the seal. As the side wall of the air-inlet piercer projects out of the plate at an angle which is substantially perpendicular to the plate (for example between about 85 degrees and about 95 degrees from the plane of the plate, preferably between about 90 degrees and about 95 degrees), the piercer side wall follows the cutting edge as the piercers are pushed into the blister in an axial direction, and the piercer side wall does not deflect the foil of the seal as the piercers are pressed through the seal. This ensures a clean cut through the foil seal, with the foil-deflecting wall deflecting only a single flap of foil into the interior of the blister.

[0031] Advantageously, each air-inlet piercer is shaped such that the cutting edge cuts a seal of a blister such that the air-inlet piercer can protrude through the seal of a blister. The shape of each air-inlet piercer, in particular, the substantially perpendicular side wall, ensures that, when cut, there is only a single seal portion or flap of seal material. This is advantageous in comparison to prior art designs with piercer designs that puncture and fracture the seal such that multiple seal portions or flaps are forced into the blister. The inventors have found, for example, that piercers which have sloping walls on either side of a single cutting edge typically rupture the seal along the cutting edge when the cutting edge is first pushed into the seal; the sloping walls then create two flaps of seal material which are pushed into the interior of the blister as the piercer plate is fully engaged with the blister. The present inventors have appreciated that having these torn or cut seal portions deflected into the blister may interfere, interrupt and / or provide resistance to the airflow inside the blister when the inhaler apparatus is used. Further, the present inventors have appreciated that the geometry of such cut seal portions is usually inconsistent and uncontrolled, when compared to moulded plastic geometry, for example. Prior art piercer designs thus produce poor efficiencies and inconsistencies when used in a drug delivery device.

[0032] Using the air-inlet piercers of the first aspect, advantageously, each air-inlet piercer is shaped such that, as the plate is gradually engaged with the seal of the blister, the seal of the blister is cut cleanly by the cutting edge of the air-inlet piercers. The foil deflecting wall then deflects a portion of the seal that has been cut or pierced such that it does not interfere with the airflow in the blister or occlude an air-inlet opening and / or the air outlet. In particular, the foil deflecting wall may deflect the cut portion of the seal such that it abuts a surface of the plate and / or lies flat against the foil deflecting wall, as the piercer is pushed fully through the seal. This may further reduce the air resistance presented by the air inlets to the airflow. By shaping the air-inlet piercers in a way that cuts the seal and then deflects the cut portion of seal against the foil deflecting wall, the present disclosure avoids the airflow problems created by ruptured flaps of seal in alternative designs.

[0033] Each air-inlet piercer comprises an air-inlet opening. The air-inlet opening is an opening in the air-inlet piercer through which air may pass. In use, when the plate and piercers are engaged with a blister and pierced through the seal, the air passes through the air-inlet opening into the blister.

[0034] The plate may be a blister-engaging plate. The air-inlet piercers and the air-outlet piercer may extend or project from the plate. The plate may be a planar surface from which the piercers extend. In use, the planar surface of the plate may abut an outer surface of a seal of a blister after the piercers have pierced the seal. Alternatively, the plate may have a shape that matches the shape of the deformed seal, for example, a catenary, or similar. This is because the force of piercing the seal may cause the seal material to stretch slightly, and become non-planar. Matching this shape with the plate will ensure that the piercers are pierced fully into the blister cavity and as such ensure that there is little or no gap between the seal material and the plate. This may advantageously control or determine the depths to which the outlet and inlet piercers enter the blister in use. The air-outlet piercer and the airinlet piercers are preferably formed as part of a single component, for example a moulded plastic component.

[0035] When the plate is not planar, the side wall may be substantially parallel to the longitudinal axis of the air-outlet piercer.

[0036] A first end of the air-inlet piercer side wall may form a piercing edge. The piercing edge may advantageously ensure a smooth cut of the seal. In other words, the piercing edge may ensure that the seal is cut such that there is only one seal portion.

[0037] A first end of the piercing edge and a first end of the foil deflecting wall preferably meet to form a piercing tip for piercing an inlet opening through the seal. The piercing tip may be the point of the air-inlet piercer that first penetrates or ruptures the seal of the blister. The piercing tip may be the part of the air-inlet piercer which projects furthest out of the plate, so that when the apparatus is engaged with a blister, the piercing tip is the first point to touch the seal of the blister. The first end of the piercing edge is the end of the piercing edge which does not meet the surface of the plate. The first end of the foil deflecting wall is the end of the foil deflecting wall that does not meet the plate.

[0038] The foil deflecting wall may be a triangular wall, or a three-sided wall. The foil deflecting wall may taper from a second end of the foil deflecting wall to the piercing tip. The second end of the foil deflecting wall meets the plate. In other words, the foil deflecting wall is shaped such that it is wider at the second end where it meets the plate, and then narrows or tapers inwardly to the piercing tip, i.e. the first end of the foil deflecting wall. This tapered shape may advantageously provide a foil deflecting wall that can pierce the seal of the blister but also provide a foil deflecting surface area that ensures the seal portion does not interfere with the airflow, as the seal portion lies flat against the foil deflecting wall. Further, this inletpiercer shape may advantageously present a streamlined profile to the airflow around the inside of the blister in use, minimising air resistance and minimising the disruption to the cyclonic airflow.

[0039] The foil deflecting wall slopes upwardly from the second end to the first end, relative to the plate. In other words, the foil deflecting wall projects progressively from the surface of the plate as it extends from the second end at the plate, to the first end at the piercing tip of the air-inlet piercer. This sloped piercer shape advantageously ensures that, when the seal is cut to form a seal portion or flap, the seal portion remains connected to the seal at least at one end and the cut seal portion is deflected into the blister by the foil deflecting wall of the piercer. This ensures that the seal portion is not pushed aside or detached such that it falls into the blister and interferes with airflow or occludes the air-outlet opening, or becomes a foreign body or fragment that could be unduly inhaled by the user.

[0040] The foil deflecting wall may slope upwardly from the second end to the first end such that the angle between the plate and the foil deflecting wall is between about 5 to 25 degrees. This acute angle advantageously ensures that, when the seal is cut to form a seal portion or flap, the seal portion remains flat and does not curl. This ensures that the seal portion does not interfere with the airflow. However, in some cases, for example, where maximal swirl is not desirable, it may be advantageous for the angle between the plate and the foil deflecting wall to be greater than about 25 degrees. However, the air-inlet piercers and the seal portions will, in this case, be less aerodynamically streamlined, and therefore may disrupt the airflow. Therefore, the present inventors have appreciated that it may be advantageous to keep this angle less than 25 degrees.

[0041] The side wall of the air-inlet piercer may be a triangular wall, or a three sided wall. The side wall may taper from the piercing edge to a second end of the side wall. In other words, the side wall is shaped such that it is wider at the first end i.e., the end that forms the piercing edge and then narrows or tapers inwardly to the second end of the side wall. At its first end the air-inlet piercer side wall may project out of the plate to its maximum height, with its height reducing gradually towards its second end. The shape of the piercer side wall may correspond to the slope of the foil deflecting wall, so that the piercer has its maximum height at the piercing tip formed by the first end of both walls, and slopes downwards to meet the plate at the second ends of the walls. This side wall shape advantageously provides an airinlet piercer that protrudes from the plate and as such, in use, when pushed all the way through the seal, the air-inlet piercer is able to move the seal portion such that it does not interfere with the airflow around the inside of the blister.

[0042] In a particularly preferred embodiment, the foil deflecting wall forms a triangular sloping roof, or ceiling, of the piercer, extending between a wide second end which meets the plate and a narrow piercing tip. The side wall preferably extends orthogonally from the plate and connects to one edge of the triangular sloping wall to form the cutting edge extending from the plate at the second end to the piercing tip at the first ends of the walls. The plane of the foil deflecting wall may be substantially perpendicular to the side wall. Alternatively the angle between the side wall and a plane of the foil deflecting wall may be between around about 80 to 120 degrees, or about 60 to 90 degrees, or about 90 to 120 degrees.

[0043] For reference, throughout the application the terms “about” or “substantially” are taken to mean + / - 10% of the respective number.

[0044] The cutting edge between the piercer side wall and the foil deflecting wall may be configured to cut a straight line in the seal of the blister. This may be advantageous because it provides a clean cut of the seal and prevents jagged cutting lines which may result in the seal rupturing and in turn splitting into a plurality of seal portions. The plan view of the cutting edge, at least, is preferably a straight line.

[0045] Each air-inlet piercer may be shaped so as to cut the seal of the blister to form a single flap in the seal of the blister. This is advantageous because it reduces the resistance to airflow that the pierced seal can cause, because a single flap can be moved out of the way such that it does not occlude the air-inlet opening or the air-outlet opening. Further advantageously, the shape of each air-inlet piercer provides a predictable and consistent cut.

[0046] Each air-inlet piercer may be shaped so as to present a streamlined profile to the airflow within the blister. Advantageously, this may reduce air resistance to airflow circulating within the blister in use.

[0047] Preferably the side wall of the inlet piercer is straight, or planar, and not curved. In some previous piercer designs, it was thought desirable to have curved piercers arranged in a ring around the central outlet, so that an upstream end of each air inlet presents a streamlined profile to the cyclonic airflow within the blister. In the present apparatus, however, the inlet piercers may have planar side walls rather than curved side walls. By providing a planar side wall, and a triangular-shaped foil deflecting wall, the present inventors have appreciated that a single foil flap may be formed which lies flat against the foil deflecting wall, and thus the air resistance and disruption to the cyclonic flow is minimised.

[0048] In use, in order to achieve a fast and stable cyclonic airflow in the blister, the inlets may be narrow in width, for example measured along a radial axis of the blister. If the inlets are relatively narrow, the space in the blister outside the inlets, between an outer edge or wall of each inlet and an outer edge or wall of the blister, is advantageously large and provides a free space for rapid cyclonic airflow, and also for classified carrier particles to circulate in, when the powdered medicament comprises API and carrier. Similarly if the inlets are relatively narrow, the space in the blister between the outlet piercer and the inlets, between an inner edge or wall of each inlet and the outlet piercer, is advantageously large and provides free space for the cyclonic airflow and to set up a low pressure cyclonic core in the region of the outlet piercer, for good classification of the API from the carrier particles.

[0049] In a particularly preferred embodiment, each air-inlet piercer may be formed by the side wall, which projects substantially perpendicularly from the plate, and the foil deflecting wall, with a third side of the piercer left open to form the air-inlet opening.

[0050] The underside of the air-inlet piercers preferably form openings through the plate, so that air may be drawn in use from the far side of the plate, through the air-inlet piercers, and out of the air-inlet opening to the interior of the blister.

[0051] The air-inlet opening may be defined by the side wall, the foil deflecting wall and the plate. The air-inlet opening is the opening in the air-inlet piercer through which air passes. In use, the air passes through the plate and through the air-inlet opening in the piercer into the blister. The air-inlet opening may be of a triangular shape. The height of the air-inlet opening may be determined by the dimensions of the side wall. The height of the air-inlet opening may be determined by the angle of the plane of the foil deflecting wall with respect to the side wall. The depth of the air-inlet opening may be determined by the width of the foil deflecting wall. The air-inlet opening may lie on a plane substantially perpendicular to the plate. The plate preferably comprises a plurality of through-holes, respectively provided at the base of each air-inlet piercer, each through-hole fluidly coupled to atmosphere. The cross-sectional area of each through-hole in the plate is preferably equal to or greater than the cross-sectional area of the respective air-inlet opening in each air-inlet piercer.

[0052] Advantageously, ensuring the cross-sectional area of the through-hole is at least as large as the cross-sectional area of the air-inlet opening results in the air flow maintaining or increasing velocity as it flows through the air-inlet piercer. As will be appreciated, when the cross-sectional area of each through-hole is greater than the cross-sectional area of the airinlet opening the velocity of the air will increase as it flows through the air-inlet piercer.

[0053] In a preferred embodiment, the air-inlet opening is triangular, with a first edge of the air-inlet opening being defined by the plate, a second edge of the air-inlet opening defined by the piercing edge of the air-inlet piercer, and a third edge of the air-inlet opening defined by a side of the foil-deflecting wall.

[0054] A second side of the foil deflecting wall may form a second cutting edge, so that the cutting edge discussed above may be referred to as a first cutting edge. The foil-deflecting wall may have a first side which meets the side wall and forms the (first) cutting edge, and a second side which provides the second cutting edge. The second side of the foil deflecting wall forming a second cutting edge may advantageously ensure that the air-inlet piercer is able to pierce the seal to provide a single flap or seal portion. This is at least because the two cutting edges cut a single seal portion, and the shape of the air-inlet piecer, in particular, the substantially perpendicular side wall, ensures the two cutting edges are the only parts of the air-inlet piercer that will cut the seal. Consequently, the likelihood of rupturing the seal into a plurality of seal portions is reduced.

[0055] The second cutting edge may run from the piercing tip to the second end of the foildeflecting wall at where the second end of the foil deflecting wall meets the plate.

[0056] Particularly preferably the foil-deflecting wall is triangular and defined by the first edge and second edge which meet at the piercing tip at the narrow first end of the piercer, and a third edge where the second end of the foil deflecting wall meets the plate.

[0057] The second cutting edge may be configured to cut a straight line in the seal of the blister. This may be advantageous because it provides a clean cut of the seal and prevents jagged cutting lines which may result in the seal rupturing and in turn splitting into a plurality of seal portions. The second cutting edge is a straight line when looking from the piercing tip to the plate.

[0058] The cutting edge and the second cutting edge may meet at the piercing tip. The cutting edge and the second cutting edge may form an acute angle therebetween. The acute angle may be between about 10 to about 80 degrees. Preferably, the acute angle may be between about 20 to about 70 degrees. More preferably, the acute angle may be between about 20 to about 50 degrees. Even more preferably, between about 20 to 35 degrees.

[0059] Each air-inlet piercer may be configured to cut a triangular flap in the seal of the blister, with two edges of the flap cut by the cutting edges of the piercer, and the third edge of the flap remaining connected to the seal. Each air-inlet piercer may be shaped such that the triangular flap is deflected into the blister by the foil-deflecting wall. The triangular flap may be deflected by the foil-deflecting wall such that it abuts the plate when the air-inlet piercer is pushed through the seal. The inventors have found that cutting a triangular flap of foil in the blister seal, with one side of the flap remaining joined to the seal and the flap deflected against the foil deflecting wall, provides an advantageously clean and predictable result which does not impede the cyclonic airflow, or the recirculation of classified carrier particles, inside the blister.

[0060] Each of the plurality of air-inlet piercers may be positioned at the same radius from the axis of the air-outlet piercer. The plate may comprise three, four or five air-inlet piercers.

[0061] Preferably, the plate comprises four air-inlet piercers. The present inventors have found that providing an inhaler apparatus with four air-inlet piercers increases the speed of airflow, in use, through the blister while also improving the stability of the airflow within the blister, leading to more efficient and predictable deagglomeration and classification of the medicament. Four air-inlet piercers typically provides the required total inlet cross-sectional area, to balance that of the air-outlet, whilst minimising the overall diameter of the blister. The present inventors have found that four-inlet piercers optimises the airflow rate and decreases the airflow resistance, which advantageously makes it easier for the user to inhale. Fewer than four air-inlets limits the airflow rate and increases the airflow resistance, meaning it is too difficult for the user to inhale; more than four air-inlets may compromise the total cross-sectional area of the air-inlets due to the relative increase in area taken up by wall thickness, which remains the same irrespective of the number of air-inlets. A higher number of smaller air-inlet piercers may also reduce the turbulence in the airflow, as the Reynolds number is reduced, through the reduction in length-scale (size). It is advantageous in cyclonic airflow systems to maximise turbulence, as cyclonic airflow relies upon the air having sufficient inertia. Too many small inlets could even reduce the Reynolds number to a point where the flow is transitional, or even laminar, in which case it is dominated by viscous losses, rather than inertial losses. Hence the geometrical constraints of having the blister just large enough to hold the required mass of formulation, whilst letting all the airflow through it with a typical strength inhalation, means that three to five air-inlets are preferable, with four being the most preferable.

[0062] The plurality of air-inlet piercers may be arranged in a circular pattern surrounding the airoutlet piercer. Preferably, the air-inlet piercers may be arranged symmetrically around the air-outlet piercer. The air-inlet piercers may be arranged such that distance between each adjacent air-inlet piercer is the same. In use, this arrangement may enhance the stability of the flow within the blister. Alternatively, each of the air-inlet piercers may be positioned at different locations with respect to the air-outlet piercer. Further alternatively, where there are four air-inlet piercers, a first pair may be positioned at location X with respect to the air-outlet piercer and a second pair of the four air-inlet piercers may be position at location Y with respect to the air-outlet piercer. Location X may have a pitch circle diameter greater than location Y. Additionally, or alternatively, location X may be displaced tangentially relative to location Y. Further, each of the four air-inlet piercers may have a different position to one another, with respect to the airoutlet piercer - e.g. positioned at X, Y, Z’ and Z”. It may be advantageous for some formulations, to have the four air-inlet piercers in a “spiral”, for example.

[0063] The air-outlet piercer may have a lateral dimension. In use, when the seal is pierced, at least a peripheral wall of the air-outlet piercer preferably extends into the blister by a distance greater than half the lateral dimension. For example, the air-outlet piercer may be in the form of a tube having a peripheral wall, and may have a sharpened lower end, or a shaped lower end, for piercing or cutting the seal. The tube may have a circular cross-section, in which case its lateral dimension may be its diameter. The fact that, in use the peripheral wall of the air-outlet piercer extends by a sufficient distance through the seal, into the blister, may have the effect that no portion of the seal displaced by the air-outlet piercer impedes airflow through the outlet, or occludes the outlet.

[0064] The piercing end of the air-outlet piercer may comprise a central, or axial, point or cutting element, protruding beyond other portions of the air-outlet piercer so as to contact the seal before other portions of the piercer. This may ensure that the seal ruptures at the centre of the piercer. The piercing end of the air-outlet piercer may further comprise a plurality of blades or edges extending radially from the central point, to cut the seal during piercing in a progressive, controlled and predictable way. This may further ensure that no portion of the seal displaced by the air-outlet piercer impedes airflow through the outlet.

[0065] The air-outlet may be greater in height than each of the air-inlet piercers. This may advantageously allow the air-outlet piercer to contact the seal of the blister first, followed by the air-inlet piercers contacting the seal. This may enhance progressive and predictable cutting of the seal during piercing.

[0066] The inhaler apparatus may further comprise a visual indicator for aiding rotational or lateral alignment of the inhaler apparatus with a blister.

[0067] Second Aspect According to a second aspect of the present disclosure, there is provided a drug delivery device for aerosolising a powdered medicament contained within a circular blister. The device comprises a blister containing the medicament. The blister comprises a circular blister pocket sealed by a pierceable seal. The device further comprises an inhaler apparatus according to the first aspect, or the third or fourth aspects discussed below.

[0068] The drug delivery device of the second aspect has a number of advantages that are discussed above in relation to the first, third or fourth aspects of the disclosure.

[0069] The powdered medicament may comprise an active pharmaceutical ingredient (API) only. In this manner, the powdered medicament may consist of API powder. In other words, the powdered medicament may comprise 100% API. Alternatively, the powdered medicament may comprise an API and a carrier. The API may be in the form of a powder, mixed with a carrier powder such as lactose powder. When the powdered medicament comprises an API mixed with a carrier the API may form up to 20% of the powdered medicament, preferably up to 15% of the powdered medicament. Alternatively, API and carrier powder may be filled into the blister without prior mixing, i.e. , the API and carrier may be filled separately into the same blister. The predominantly cyclonic flow regime within the blister, promoted by the inhaler apparatus according to the present disclosure, will mix the API and carrier during use. The present inventors have appreciated that it is advantageous to be able to have the API and carrier separate. This is because it allows for much higher ratios of API to carrier, for example, 50% API to 50% carrier, or even higher, for example, 75% API to 25% carrier. Effectively mixing the API and carrier during the inhalation overcomes the difficulty in achieving high strength blends prior to filling the blister, as it is difficult to achieve homogeneity, in other words, consistency in the mixture, with blends that typically contain greater than 15% API. This is particularly advantageous for low potency medicaments, that require much higher doses of API.

[0070] The dimensions of the outlet and the inlets may be selected so that the rate of airflow inhaled by a user through the inhaler is limited by airflow through the outlet.

[0071] The inhaler apparatus may further comprise a visual indicator for aiding rotational or lateral alignment of the inhaler apparatus with a blister. Alternatively, the blister and / or the inhaler apparatus may comprise co-operating mechanical shapes or keys to ensure alignment. The user may then inhale through the inhaler apparatus, drawing air through the air-outlet piercer. This, in turn, draws air through the air-inlet piercers and creates a cyclonic airflow within the blister, while also accelerating the medicament radially outwardly and carrying the medicament circumferentially around the blister.

[0072] When the powdered medicament comprises an API and a carrier, the particles of the API are smaller and lighter than the carrier particles (which might, for example, be lactose particles) and therefore the API particles are preferentially drawn out of the blister through the airoutlet piercer for inhalation by the user.

[0073] The depth of the blister may be greater than 1.2 times the distance which the air-outlet piercer extends into the blister, and may preferably be 1.5 or 2 or 3 times the distance which the air-outlet piercer extends into the blister. The blister may be sufficiently deep such that the air-outlet or the air-inlet piercers do not puncture the blister tray in use. It is known to use coldform material to make blisters, this material may be tough and as such it is advantageous to avoid contact between the air-inlet piercer, in particular, the piercing tip and the blister. This is because, due to the material of the blister, contact between the two could damage or blunt the air-inlet piercers, in particular, the piercing tips. This in turn, could reduce the longevity of the air-inlet piercers and the inhaler apparatus as a whole. Therefore, the present inventors have appreciated that it is advantageous to maintain a clearance or distance between the relatively sharp tips of the piercers and the blister tray.

[0074] The blister pocket may have a parabolic cross section. The inventors have found that moulding a blister pocket with a parabolic cross section may enable formation of a blister pocket with lower strain at its outer edge than a circular-section blister pocket of the same depth (so as to accommodate an air-outlet piercer of a given size). Use of a parabolic cross section may be particularly advantageous if a blister pocket is formed from a sheet of material comprising an aluminium vapour barrier (such as a plastic-aluminium-plastic laminate), which may be damaged by straining the material beyond a certain threshold, typically 32% strain. When such a material is used, a deeper blister pocket may advantageously be moulded using a parabolic shape rather than a circular, or spherical, shape. The inventors have found that a parabolic shape may advantageously provide the greatest enclosed volume and depth for a given diameter.

[0075] Preferably, the blister pocket is shaped to enhance cyclonic flow within the blister. Typically, the blister may comprise a blister pocket sealed with a flat, or planar, seal such as a foil seal. At the outer edge of the blister, an angle is therefore defined between a peripheral wall of the blister pocket and the seal. During inhalation through the drug-delivery device, the medicament is accelerated outwardly within the blister, carried by the cyclonic flow. In a preferred embodiment, therefore, the angle between the peripheral wall of the blister pocket and the seal is advantageously as large as possible, for example being greater than 30° or 40°, and up to 50°, 60°, 70°, 80° or 90°.

[0076] At the same time, the blister pocket should be deep enough to accommodate the air-outlet piercer and the air-inlet piercers. Blister pockets are conventionally moulded by deforming flat sheets of material. This may be carried out by methods including deep drawing and cold forming. Any method may be used to form blisters embodying the invention, but the blister pocket should advantageously have a smooth inner surface to optimise the cyclonic flow. Deep drawing tends to introduce wrinkles into the material of the blister pocket and so cold forming may be preferred.

[0077] One way to achieve a sufficiently deep blister pocket with a relatively large angle between the peripheral wall of the blister pocket and the seal is to use a blister pocket with a crosssection shaped as a sector of a circle, such as a hemisphere. This shape may also maximise the volume of the blister pocket. However, when a circular-section blister pocket is formed the strain in the material is greatest at the outer edge of the blister pocket. The inventors have found that moulding a blister pocket with a parabolic cross section may enable formation of a blister pocket with lower strain at its outer edge than a circular-section blister pocket of the same depth (so as to accommodate an air-outlet piercer of a given size). Use of a parabolic cross section may be particularly advantageous if a blister pocket is formed from a sheet of material comprising an aluminium vapour barrier (such as a plastic- aluminium-plastic laminate), which may be damaged by straining the material beyond a certain threshold, typically 32% strain. When such a material is used, a deeper blister pocket may advantageously be moulded using a parabolic shape rather than a circular, or spherical, shape.

[0078] It should be noted that, advantageously, embodiments of the disclosure may not require any structure or features within the blister, so that the blister only comprises, or consists of the blister pocket and the seal, with the medicament sealed inside. This may facilitate manufacture of the blister. In addition, no deformation of the blister or modification of the blister is required during use of the drug-delivery device, except for the piercing of the seal. The blister may therefore be fabricated from conventional materials, selected for optimum compatibility with the medicament. Further, the device may be configured such that all of the air inhaled by a user passes through the blister.

[0079] In different embodiments of the present disclosure, the inhaler apparatus may engage with the blister in different ways. For example, the inhaler apparatus may move towards the seal in a perpendicular direction or it may be hinged so that it pivots into engagement with the blister.

[0080] Third Aspect

[0081] The present disclosure also relates an inhaler apparatus for aerosolising a powdered medicament contained within a circular blister. The apparatus may comprise a plate for engaging a circular blister. The plate may comprise an air-outlet piercer for piercing an air outlet through a seal of the blister. The air-outlet piercer may be axially positioned in the blister, in use. The plate may further comprise a plurality of air-inlet piercers surrounding the air-outlet piercer. Each air-inlet piercer may comprise a piercing tip for piercing an inlet opening through the seal. Each air-inlet piercer may comprise an air-inlet opening, facing away from the air-outlet piercer, for directing air into the blister when air is drawn through the air outlet. The air-inlet opening may lie on a plane substantially perpendicular to the plate and at an angle of between about 45 to 135 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip.

[0082] According to a third aspect of the present disclosure, there is provided an inhaler apparatus for aerosolising a powdered medicament contained within a circular blister. The apparatus comprises a plate for engaging a circular blister. The plate comprises an air-outlet piercer for piercing an air outlet through a seal of the blister. The air-outlet piercer being axially positioned in the blister. The plate further comprises a plurality of air-inlet piercers surrounding the air-outlet piercer. Each air-inlet piercer comprises a piercing tip for piercing an inlet opening through the seal. Each air-inlet piercer comprises an air-inlet opening, for directing air into the blister when air is drawn through the air outlet. The air-inlet opening lies on a plane substantially perpendicular to the plate and at an angle of between about 45 to 135 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip.

[0083] The powdered medicament may comprise an active pharmaceutical ingredient (API) only. In this manner, the powdered medicament may consist of API powder. In other words, the powdered medicament may comprise 100% API. Alternatively, the powdered medicament may comprise an API and a carrier. The API may be in the form of a powder, mixed with a carrier powder such as lactose powder. When the powdered medicament comprises an API mixed with a carrier the API may form up to 20% of the powdered medicament, preferably up to 15% of the powdered medicament. Alternatively, API and carrier powder may be filled into the blister without prior mixing, i.e. , the API and carrier may be filled separately into the same blister. The predominantly cyclonic flow regime within the blister, promoted by the inhaler apparatus according to the present disclosure, will mix the API and carrier during use. The present inventors have appreciated that it is advantageous to be able to have the API and carrier separate. This is because it allows for much higher ratios of API to carrier, for example, 50% API to 50% carrier, or even higher, for example, 75% API to 25% carrier. Effectively mixing the API and carrier during the inhalation overcomes the difficulty in achieving high strength blends prior to filling the blister, as it is difficult to achieve homogeneity, in other words, consistency in the mixture, with blends that typically contain greater than 15% API. This is particularly advantageous for low potency medicaments, that require much higher doses of API.

[0084] During the development of the present inhaler apparatus, the inventors had previously shaped each inlet so that, in use, air drawn through the inlet enters the blister in a tangential direction, and so that an upstream end of each air inlet presented a streamlined profile to the cyclonic airflow within the blister. In some of these designs, the air-inlet openings and the piercing tips lay on radial planes extending radially from the centre of the outlet, so that incoming air was travelling in a tangential direction. In these embodiments an angle of effectively 0 degrees was formed between the planes of the air-inlet openings and the extending between a centre of the air-outlet piercer and the piercing tip. Following further work, the inventors have now appreciated that superior results may be achieved by orienting the air-inlet opening at a different angle, so that air drawn into the blister through the inlets does not enter in a tangential direction only.

[0085] The present inventors have appreciated that by positioning the air-inlet opening such that it lies on a plane substantially perpendicular to the plate and at an angle of between about 45 to about 135 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip, an outward radial vector component is introduced into the airflow within a blister. Rather than the incoming airflow having a purely tangential vector component, the air entering through the inlets may thus have an outward radial vector component in addition to a tangential component. In this context, outward means towards the perimeter of the plate and / or blister. In use, air drawn through the inlet openings enters the blister in a direction dictated by the angular orientation of the inlets to create a cyclonic airflow within the blister.

[0086] When the powdered medicament comprises an API and a carrier, by angling the air inlet openings to produce airflow with an outward radial component as it enters the blister in use, higher levels of deagglomeration can be achieved than are possible with air inlets that are arranged on radial planes to produce purely tangential airflow. This is because the air-inlet opening being angled in such a way may counterintuitively, but advantageously, direct medicament within the air-inlet piecer outwardly within the blister, enhancing deagglomeration. As the medicament circulates, agglomerated particles collide with the walls and with one another, and the API is separated from the carrier.

[0087] When the powdered medicament comprises API only in particular, the present inventors have appreciated that introducing an outward radial flow component into the airflow, such that the airflow has both a tangential and an outward radial air flow component is advantageous for the following reasons. Adding this radial flow component to the airflow may reduce airflow resistance as a cyclonic flow is established inside the blister in use. Further, adding a radial flow component to the airflow may reduce the swirl number of the cyclonic airflow established in the blister. This may counterintuitively, but advantageously, allow for better particle dispersion. Further, a reduced swirl number may provide a more controlled and uniform flow pattern, which facilitates an even distribution of particles and high separation efficiency. Consequently, this may result in higher mass output of the API from the blister. In other words, a higher percentage of the API initially held within the blister is aerosolised and evacuated from the outlet for inhalation by the user.

[0088] The present inventors have appreciated that reducing the swirl number is particularly advantageous when the powdered medicament comprises API only. This is because if the swirl number is too high, the centrifugal force will be too high and as such the API particles will get stuck at the edge of the blister because there is not enough aerodynamic drag or power to overcome this force and pull or free the API from the edge of the blister such that it can be drawn towards the outlet. Therefore, by reducing the swirl number and providing a more controlled and uniform flow pattern, the inhaler apparatus according to the third aspect assists in providing effective aerosolisation and evacuation of the API powder. The swirl number S of a fluid flow is defined as the ratio of the axial flux of angular momentum to the axial flux of the axial momentum.

[0089] (Eq. 1)

[0090] The airflow induced by the air-inlet piercers according to the third aspect accelerates the particles radially outwardly so that only the smallest, lightest particles can be carried by the airflow through the outlet. This advantageously ensures an effective dose is provided for inhalation by the user.

[0091] Preferably, the air-inlet opening is configured to, or positioned to, introduce an outward radial flow component to air passing through the air-inlet piercer. This advantageously increases the average tangential velocity at the edge of the blister and as such provides more effective scouring of particles at the edge of the blister. This in turn may provide more effective aerosolisation and evacuation of the API powder. In particular, this may provide a higher mass output of API or a higher concentration of API in the emitted dose.

[0092] Preferably, the air-inlet opening is positioned to induce a tangential flow component to air passing through the air-inlet piercer. The air-inlet opening faces away from the air-outlet piercer. As such, in use, the air-inlet opening faces towards the edge of the blister.

[0093] As discussed in relation to the first aspect, the piercing tip is the point of the air-inlet piercer that first penetrates or ruptures the seal of the blister.

[0094] When the powdered medicament comprises API and carrier, the air-inlet opening may lie on the plane substantially perpendicular to the plate and at an angle a of between about 50 to 120 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip. Preferably, between about 60 to 90 degrees. More preferably, between about 70 to 80 degrees.

[0095] When the powdered medicament comprises API only, the air-inlet opening may lie on the plane substantially perpendicular to the plate and at an angle a of between about 50 to 115 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip. Preferably, between about 70 to 115 degrees. More preferably, between about 80 to 110 degrees. Even more preferably, between about 90 and 105 degrees. Fourth Aspect

[0096] According to a fourth aspect of the present disclosure, there is provided a drug delivery device for aerosolising a powdered medicament contained within a circular blister.

[0097] The device comprises a blister containing the medicament. The blister comprises a circular blister pocket sealed by a pierceable seal. The blister may be a blister as substantially described herein with reference to the second aspect of the present disclosure. The device further comprises an inhaler apparatus according to the third aspect.

[0098] The powdered medicament may comprise an active pharmaceutical ingredient (API). The powdered medicament may consist of an API. Alternatively, the powdered medicament may comprise an API and a carrier. When the powdered medicament comprises an API mixed with a carrier the API may form up to 20% of the powdered medicament, preferably up to 15% of the powdered medicament. Alternatively, API and carrier powder may be filled into the blister without prior mixing, i.e. , the API and carrier may be filled separately into the same blister. The predominantly cyclonic flow regime within the blister, promoted by the inhaler apparatus according to the present disclosure, will mix the API and carrier during use. The present inventors have appreciated that it is advantageous to be able to have the API and carrier separate. This is because it allows for much higher ratios of API to carrier, for example, 50% API to 50% carrier, or even higher, for example, 75% API to 25% carrier. Effectively mixing the API and carrier during the inhalation overcomes the difficulty in achieving high strength blends prior to filling the blister, as it is difficult to achieve homogeneity, in other words, consistency in the mixture, with blends that typically contain greater than 15% API. This is particularly advantageous for low potency medicaments, that require much higher doses of API.

[0099] Fifth Aspect

[0100] The present disclosure also provides an inhaler apparatus for aerosolising a powdered medicament contained within a circular blister. The apparatus may comprise a plate for engaging a circular blister. The plate may comprise an air-outlet piercer for piercing an air outlet through a seal of the blister. The air-outlet piercer may be axially positioned in the blister. The plate may further comprise a plurality of air-inlet piercers surrounding the airoutlet piercer. Each air-inlet piercer may comprise a side wall. The side wall may face the air-outlet piercer. Where the side wall may lie on a side wall plane orthogonal to both a radial plane, wherein the radial plane passes through a central axis of the air-outlet piercer, and the plate. Each air-inlet piercer may comprise a piercing tip for piercing an inlet opening through the seal of the blister. The piercing tip may be located at a first end of the side wall. Each air-inlet piercer may be respectively positioned on the plate such that the side wall plane is at a distance of between about 25% and about 75% of the radius of the blister from the central axis of the air-outlet piercer and / or such that the piercing tip is at a distance of up to about 50% of the radius of the blister from a first side of the radial plane or at a distance of up to about 50% of the radius of the blister from a second side of the radial plane.

[0101] According to a fifth aspect of the present disclosure, there is provided an inhaler apparatus for aerosolising a powdered medicament contained within a circular blister. The apparatus comprises a plate for engaging a circular blister. The plate comprises an air-outlet piercer for piercing an air outlet through a seal of the blister. The air-outlet piercer is axially positioned in the blister. The plate further comprises a plurality of air-inlet piercers surrounding the airoutlet piercer. Each air-inlet piercer comprises a side wall facing the air-outlet piercer. Where the side wall lies on a side wall plane orthogonal to both a radial plane, wherein the radial plane passes through a central axis of the air-outlet piercer, and the plate. Each air-inlet piercer comprises a piercing tip for piercing an inlet opening through the seal of the blister. The piercing tip is located at a first end of the side wall. Each air-inlet piercer is respectively positioned on the plate such that the side wall plane is at a distance of between about 25% and about 75% of the radius of the blister from the central axis of the air-outlet piercer and / or such that the piercing tip is at a distance of up to about 50% of the radius of the blister from a first side of the radial plane or at a distance of up to about 50% of the radius of the blister from a second side of the radial plane.

[0102] The powdered medicament may comprise an active pharmaceutical ingredient (API). The powdered medicament may consist of an API. Alternatively, the powdered medicament may comprise an API and a carrier. When the powdered medicament comprises an API mixed with a carrier the API may form up to 20% of the powdered medicament, preferably up to 15% of the powdered medicament. Alternatively, API and carrier powder may be filled into the blister without prior mixing, i.e. , the API and carrier may be filled separately into the same blister. The predominantly cyclonic flow regime within the blister, promoted by the inhaler apparatus according to the present disclosure, will mix the API and carrier during use. The present inventors have appreciated that it is advantageous to be able to have the API and carrier separate. This is because it allows for much higher ratios of API to carrier, for example, 50% API to 50% carrier, or even higher, for example, 75% API to 25% carrier. Effectively mixing the API and carrier during the inhalation overcomes the difficulty in achieving high strength blends prior to filling the blister, as it is difficult to achieve homogeneity, in other words, consistency in the mixture, with blends that typically contain greater than 15% API. This is particularly advantageous for low potency medicaments, that require much higher doses of API.

[0103] The side wall faces the air-outlet piercer. In other words, the side wall is adjacent the airoutlet piercer. The side wall being the part I section of the air-inlet piercer that is closest in distance to the air-outlet piercer.

[0104] The air-inlet piercers may be positioned relative to the centre of the plate within these limits, while still providing desirable results. Positioning the air-inlet piercers at different points within these ranges alters the position at which air enters the blister in use, and may advantageously affect the properties of the cyclonic airflow established within the blister. For example the positions of the air-inlet piercers may be selected to reduce or increase the swirl number of the cyclonic airflow in order to suit a desired flow regime for the inhaler apparatus. The present inventors have appreciated that it is advantageous to be able to select the position of the air-inlet piercers, within the ranges described herein, on the plate depending on the composition of the powdered medicament, as discussed in more detail below. In particular, depending on the ratio of API to carrier in the powdered medicament.

[0105] Advantageously, each air-inlet piercer being respectively positioned on the plate such that the side wall plane is at a distance of between about 25% and about 75% of the radius of the blister from the central axis of the air-outlet piercer, allows for the positions of the air inlets to be selected based on the desired flow regime. The location of the air-inlet piercers, and thus the position of the air inlets in the blister in use, may be varied within this range to determine the properties of the cyclonic airflow established inside the blister.

[0106] For example, when the powdered medicament comprises an API and a carrier, the present inventors have appreciated that it may be advantageous to provide an inhaler apparatus whereby the distance between the side wall plane and the central axis of the air-outlet piercer is greater, in comparison, to the distance when the powdered medicament comprises API only. This is because when the powdered medicament is carrier based it is advantageous to have a higher swirl number, such that, in use, more effective deagglomeration and classification of API from the carrier can be provided. The present inventors have appreciated that the swirl number may be increased by increasing the distance between the side wall plane and the central axis of the air-outlet piercer. More effective deagglomeration and classification of API from the carrier ensures that the smaller and lighter API particles are free to be drawn into the outlet for inhalation by the user. In turn, this provides a higher mass output of pure API and / or a higher concentration of API in the emitted dose. As such, in use, the inhaler apparatus advantageously provides more effective delivery of the drug.

[0107] The inventors have found that if the side wall plane is closer than 25% of the radius of the blister to the central axis of the air outlet, or closer than 75% of the radius of the blister to the perimeter of the blister, then the air-inlet piercers can interfere with the establishment of cyclonic airflow in the blister and reduce the efficiency of aerosolisation and / or deagglomeration. Further, if the side wall plane is too close to the perimeter of the blister, it may interfere with the blister itself.

[0108] When the powdered medicament comprises API only, each air-inlet piercer may be positioned such that the distance between the side wall plane and the central axis of the airoutlet is between about 25% and 40%. More preferably between about 25% and 30%. This distance has been found by the present inventors to be particularly effective and advantageous when the powdered medicament comprises API only, as it reduces the swirl number.

[0109] When the powdered medicament comprises API and a carrier, each air-inlet piercer may be positioned such that the distance between the side wall plane and the central axis of the airoutlet is between about 40% and about 60%. More preferably between about 45 % and 55%. Even more preferably, between about 47% and 52% or about 50%. This distance has been found by the present inventors to be particularly effective and advantageous when the powdered medicament comprises API and carrier.

[0110] Advantageously, positioning each air-inlet piercer on the plate such that the side wall plane is at a distance of between about 45% and 55% of the radius of the blister from the central axis of the air-outlet piercer, has been found to optimise the deagglomeration of an API from a carrier within a blister and as such provide improved delivery of a drug for inhalation by a user. This is because increasing the swirl number increases the collision between the particles which assists in obtaining the finer and smaller deagglomerated API particles. In other words, the classification of the carrier is increased or maximised. Increasing the classification of the carrier in the blister is advantageous because it reduces the amount of carrier that is inhaled for a given dose of API. Consequently, the effective concentration of the emitted dose is higher i.e., a higher proportion of the emitted dose is respirable API particles. Further, positioning each air-inlet piercer within this particular range increased the stability of the airflow. This combination, and in particular, improving the stability of the airflow, advantageously results in more efficient and predictable deagglomeration and classification of the medicament.

[0111] For example, when the blister has a diameter of about 22.5 mm, each air-inlet piercer may be respectively positioned on the plate such that the side wall plane is at a distance of between 3 mm to 8 mm, or between 4 mm and 7 mm, from the central axis of the air-outlet piercer.

[0112] Each air-inlet piercer may be respectively positioned on the plate such that the side wall plane is at a distance of between about 25% and about 75% of the radius of the portion of the plate that engages with the inner radial edge of the blister.

[0113] Preferably the piercer side wall lies along a chord (a straight line segment whose endpoints both lie on the perimeter of the circular blister, or the perimeter of the plate if the plate is also circular) relative to the circular blister. The side wall plane may thus lie along a chord relative to the circular blister.

[0114] The location of the piercing tip on the side wall plane may be selected depending on the required flow characteristics. For example the piercing tip may be positioned on a radial plane extending from the central axis of the outlet, or the piercing tip may be positioned on either side of that radial plane.

[0115] Advantageously, each air-inlet piercer being respectively positioned on the plate such that the piercing tip is at a distance of up to about 50% of the radius of the blister from a second side of the radial plane, allows for a radial flow component to be introduced into the flow regime. When the piercing tip lies on the second side of the radial plane, the radial plane intersects the air-inlet piercer.

[0116] The present inventors have appreciated that introducing a radial flow component into the airflow is advantageous for the following reasons. Adding a radial flow component to the airflow reduces the airflow resistance. Further, adding a radial flow component to the airflow reduces the swirl number. The present inventors have appreciated that introducing a radial flow component is particularly advantageous when the powdered medicament comprises API only. In other words, when the powdered medicament is non-carrier based medicament. This is because adding a radial flow component to the airflow and reducing the swirl number advantageously reduces the likelihood of agglomeration and accumulation of the smaller API particles, particularly at the edge of the blister, allowing for better particle dispersion and separation. Further, a reduced swirl number may provide a more controlled and uniform flow pattern, which facilitates a more even distribution of particles and higher separation efficiency. This in turn leads to a higher mass output of the finer and smaller API particles and as such a dose with a higher concentration of API can be delivered to the user.

[0117] In use, the addition of the radial flow component ensures that the airflow it directed towards the edge of the blister, rather than tangentially, as seen with the known prior art.

[0118] Consequently, the average tangential velocity and scouring power at the edge of the blister is increased, which in turn, provides more effective clearance at the edge of the blister and as such prevents the API particles from being stuck at the edge of the blister. This allows the particles to be free to be drawn into the outlet for inhalation by the user and as such, results in an improved emitted dose of API to the patient.

[0119] The purpose of the air inlets is to direct inflowing air in a radial and / or tangential direction within the blister. To achieve this, all of the air inlets may be orientated in the same direction, clockwise or anticlockwise.

[0120] When the powdered medicament comprises API and carrier, each air-inlet may be respectively positioned on the plate such that the piercing tip is at a distance of up to about 20% of the radius of the blister from the first side of the radial plane or up to about 20% of the radius of the blister from the second side of the radial plane. More preferably, up to about 10%. Even more preferably, the piercing tip intersects the radial plane i.e., the distance between the piercing tip and the radial plane is 0 mm.

[0121] When the powered medicament comprises API only, each air-inlet may be respectively positioned on the plate such that the piercing tip is at a distance of between about 20% to 50% of the radius of the blister from the second side of the radial plane. Preferably, the piercing tip is at a distance of between about 30% to 50% of the radius of the blister from the second side of the radial plane. More preferably, between about 35% and 50%. Even more preferably, between about 35% and 45%.

[0122] Each air-inlet piercer may be positioned so as to introduce both a tangential flow component and the radial flow component to air passing through the air-inlet piercer.

[0123] When the powdered medicament comprises API and carrier, each air-inlet may be respectively positioned on the plate such that the side wall plane is at an angle of between about 60 degrees and 90 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip. Preferably between about 75 degrees and 90 degrees. More preferably, about 90 degrees.

[0124] When the powdered medicament comprises API only, each air-inlet piercer may be respectively positioned on the plate such that the side wall plane is at an angle p of between about 45 degrees and about 80 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip. More preferably, between about 45 degrees and about 70 degrees. Even more preferably, between about 45 degrees and about 60 degrees. Advantageously, the present inventors have appreciated that this positioning results in substantial improvements with regards to the percentage of the dose emitted to the user, in comparison to known prior art devices. In other words, the amount of API remaining in the blister after inhalation is significantly reduced, in comparison to known prior art devices.

[0125] Each air-inlet piercer may be respectively positioned on the plate such that the side wall plane is at a distance of between about 30% and about 70% of the radius of the blister from the central axis of the air-outlet piercer. Preferably, between about 40% and about 60%. More preferably, between about 45% and 55%. Even more preferably, between about 47% and 52% or about 50%. This has been found by the present inventors to be particularly effective and advantageous when the powdered medicament comprises API and carrier.

[0126] The plurality of air-inlet piercers may be positioned at the same radius from the axis of the air-outlet piercer. The plate may comprise three, four or five air-inlet piercers. Preferably, the plate comprises four air-inlet piercers. The present inventors have found that providing an inhaler apparatus with four air-inlet piercers increases the speed of airflow, in use, through the blister while also improving the stability of the airflow within the blister, leading to more efficient and predictable deagglomeration and classification of the medicament.

[0127] The plurality of air-inlet piercers may be arranged in a circular pattern surrounding the airoutlet piercer. Preferably, the air-inlet piercers may be arranged symmetrically around the air-outlet piercer. The air-inlet piercers may be arranged such that distance between each adjacent air-inlet piercer is the same. In use, this arrangement may enhance the stability of the flow within the blister.

[0128] Alternatively, each of the air-inlet piercers may be positioned at different locations with respect to the air-outlet piercer. Further alternatively, where there are four air-inlet piercers, a first pair may be positioned at location x with respect to the air-outlet piercer and a second pair of the four air-inlet piercers may be position at location y with respect to the air-outlet piercer. Location x and location y being different to one another.

[0129] Each air-inlet piercer comprises an air-inlet opening, for directing air into the blister when air is drawn through the air outlet.

[0130] It may be noted that in preferred embodiments of the disclosure, the carrier particles which are classified, or separated, from the API particles during inhalation may advantageously be retained in the blister. Any API particles which are not delivered to the user are also retained in the blister. This simplifies operation of the drug-delivery device, because no portion of the medicament may be retained in the inhaler apparatus, or is lost into the environment, and any carrier particles or API not inhaled by the user are conveniently and safely disposed of by disposing of the used blister.

[0131] Embodiments of the disclosure may advantageously be used for high-payload drug-delivery devices, in which a large quantity of powdered medicament (for example 50 mg and above) is contained within the blister. To deagglomerate, or classify, a larger medicament payload in particular, it is preferable to maximise the air flow rate through an inhaler for a given inhalation pressure exerted by a user. This may maximise the power (pressure drop multiplied by flow rate) available to deagglomerate and classify the medicament. To that end, all of the air inhaled by the user advantageously passes through the air inlets, the blister and the air outlet (although in some embodiments there may be a small air bypass to modify the sensation felt by the user inhaling through the device, though it is appreciated that any bypass air is effectively wasted power, so the intention is to pass all the airflow through the blister, to maximise the power available to deagglomerate the formulation).

[0132] The drug-delivery device is preferably a high-resistance or ultra-high-resistance inhaler. This may advantageously allow a consistent airflow through the device to be achieved by users capable of applying different inspiratory efforts.

[0133] A high-resistance inhaler typically allows an air flow rate of less than about 60 l / min when a differential pressure of 4 kPa is applied across the inhaler, and an ultra-high resistance inhaler allows a flow rate of less than about 45 l / min at 4 kPa. In a preferred embodiment of the disclosure an air flow rate as low as 40 l / min or less may be achieved when a differential pressure of 4 kPa is applied. As well as allowing a consistent airflow through the device for different users, the low flow rate through the inhaler apparatus and the blister is partly a consequence of high viscous momentum transfer losses between the free vortex (outer region of blister) and the forced vortex (inner region of blister), during inhalation. These momentum transfer losses enhance classification of the API from the carrier within the blister, so that a greater proportion of the API is inhaled and a greater proportion of the carrier is retained in the blister after inhalation. In a particularly-preferred embodiment, the inventors have achieved very high classification levels of 94%. The presence of powder within the blister during inhalation can affect its airflow resistance, by reducing viscous momentum transfer losses, as the powder itself effectively blurs the boundary between the free and the forced vortices. The present inventors have factored this effect into the preferred embodiments, in that the desired airflow resistance is achieved with the presence of formulation.

[0134] Sixth Aspect

[0135] According to a sixth aspect of the present disclosure, there is provided a drug delivery device for aerosolising a powdered medicament contained within a circular blister.

[0136] The device comprises a blister containing the medicament. The blister comprises a circular blister pocket sealed by a pierceable seal. The blister may be a blister as substantially described herein with reference to the second aspect of the present disclosure. The device further comprises an inhaler apparatus according to the fifth aspect.

[0137] The powdered medicament may comprise an active pharmaceutical ingredient (API). The powdered medicament may consist of an API. Alternatively, the powdered medicament may comprise an API and a carrier. When the powdered medicament comprises an API mixed with a carrier the API may form up to 20% of the powdered medicament, preferably up to 15% of the powdered medicament. Alternatively, API and carrier powder may be filled into the blister without prior mixing, i.e. , the API and carrier may be filled separately into the same blister. The predominantly cyclonic flow regime within the blister, promoted by the inhaler apparatus according to the present disclosure, will mix the API and carrier during use. The present inventors have appreciated that it is advantageous to be able to have the API and carrier separate. This is because it allows for much higher ratios of API to carrier, for example, 50% API to 50% carrier, or even higher, for example, 75% API to 25% carrier. Effectively mixing the API and carrier during the inhalation overcomes the difficulty in achieving high strength blends prior to filling the blister, as it is difficult to achieve homogeneity, in other words, consistency in the mixture, with blends that typically contain greater than 15% API. This is particularly advantageous for low potency medicaments, that require much higher doses of API. In further aspects, the disclosure may also advantageously provide a method for aerosolising a powdered medicament contained within a circular blister, comprising a blister pocket sealed by a pierceable seal. The blister is engageable with an inhaler apparatus according to the first, third or fifth aspect. The method may then comprise the steps of bringing the inhaler apparatus into engagement with the blister to pierce the seal with the airoutlet and air-inlet piercers, and a user inhaling through an inhaler mouthpiece coupled to the outlet, so that the blister forms a cyclone for deagglomerating and / or classifying the medicament. Air is drawn from the blister through the outlet opening in an air-outlet direction, and the air inlets surround the air outlet and direct the air to the air-outlet direction to form a cyclonic airflow within the blister.

[0138] The powdered medicament may comprise an API only. Alternatively, the powdered medicament may comprise an API and carrier.

[0139] In even further aspects, the disclosure may also advantageously provide a method for manufacturing an inhaler apparatus according to the first, third or fifth aspects.

[0140] In particular, the method for manufacturing may comprise, when the inhaler apparatus is for aerosolising a powdered medicament comprising an active pharmaceutical ingredient (API) and a carrier contained within a circular blister, positioning each air-inlet piercer on the plate such that the side wall plane is at a distance of between about 25% and about 75% of the radius of the blister from the central axis of the air-outlet piercer.

[0141] Preferably, the method comprises selecting a position for each air-inlet piercer on the plate such that the side wall plane is at a distance of between about 40% and 65%. Preferably, between about 40% and about 60%. More preferably, between about 45% and 55%. Even more preferably, between about 47% and 52% or between about 50%.

[0142] This may advantageously provide a method of manufacturing that results in an inhaler apparatus that, in use, increases the swirl number due to the position of the air-inlet piercer and as such provides more effective deagglomeration and classification of the API particle from the carrier.

[0143] Alternatively or additionally, the method for manufacturing may comprise selecting a position for each air-inlet piercer such that the piercing tip is at a distance of up to about 50% of the radius of the blister from a first side of the radial plane or at a distance of up to about 50% of the radius of the blister from a second side of the radial plane. In particular, when the inhaler apparatus is for aerosolising a powdered medicament comprising an active pharmaceutical ingredient (API) only, the method may comprise selecting a position for each air-inlet piercer such that the piercing tip is at a distance of up to about 50% of the radius of the blister from a second side of the radial plane. This may advantageously introduce a radial flow component into the airflow, which the present inventors have appreciated improves evacuation of the API particles, particularly, when the powdered medicament comprises API particles only.

[0144] Preferably, the method may comprise selecting a position each air-inlet piercer such that the piercing tip is at a distance of up to about 50% of the radius of the blister from a second side of the radial plane.

[0145] Preferably, the method may comprise selecting a position for each air-inlet piercer such that the piercing tip is at a distance of up to between about 20% and 50% of the radius of the blister from a second side of the radial plane. More preferably, the piercing tip is at a distance of between about 30% to 50% of the radius of the blister from the second side of the radial plane. Even preferably, between about 35% and 50% or preferably, between about 35% and 45%

[0146] It will be appreciated that features described in relation to one aspect of the present disclosure may also be applied equally to all of the other aspects of the present disclosure. Features described in relation to the first aspect of the present disclosure may be applied equally to the second aspect of the present disclosure and vice versa. Features of the inhaler apparatus described in relation to the first aspect may be applied, mutatis mutandis, to the inhaler apparatus of the third aspect, for example.

[0147] It will further be appreciated that particular combinations of the various features described and defined in any aspects of the disclosure may be implemented and / or supplied and / or used independently.

[0148] Description of Specific Examples of the Disclosure

[0149] Specific examples of the disclosure will now be described with reference to the Figures, in which:

[0150] Figure 1 shows a perspective view of a drug-delivery apparatus according to an embodiment not within the scope of the claims (with a blister shown cut away for clarity); Figure 2a shows bottom view of the inhaler apparatus according to the present disclosure;

[0151] Figure 2b shows a perspective view of the inhaler apparatus of Figure 2(a); and

[0152] Figures 3a to 3d shows a perspective view of inhaler apparatuses with varying positioning of the air-inlet piercers according to the present disclosure;

[0153] Figure 4 is the inhaler apparatus as shown in Figure 1 and illustrates the positioning of the air-inlet opening;

[0154] Figure 5 shows a bottom view of an inhaler apparatus according to the present disclosure with the air-inlet piercers located in a first position and illustrates the side wall plane;

[0155] Figures 6a to 6d shows top cross-sectional views of a drug delivery device with different airinlet piercer positions and the respective tangential velocity within the blister predicted by CFD;

[0156] Figures 7a to 7d shows average tangential velocity map data obtained from cross sectional views of a quarter of a blister with the air-inlet piercer positions of Figures 6a to 6d respectively;

[0157] Figures 8a to 8d shows maximum tangential velocity map data obtained from cross sectional views of a quarter of a blister with the air-inlet piercer positions of Figures 6a to 6d respectively;

[0158] Figure 9 shows a graph of mass retention of the powdered medicament, which is comprised of almost all carrier particles (%) based on the different air-inlet piercer positions of Figures 6a to 6d;

[0159] Figure 10 shows a graph of emitted active concentration (%) based on the different air-inlet piercer positions of Figures 6a to 6d;

[0160] Figure 11 is a bar chart that shows for each air-inlet piercing position as shown in Figure 6a to 6d and the RS01-UHR, the percentage of the total retained powdered medicament substitute mass and also the proportion of API originally contained within the blister that was emitted during inhalation;

[0161] Figure 12 is a bar chart that shows for each air-inlet piercing position as shown in Figure 6a to 6d and the RS01-UHR, the total emitted mass (mg) and of that total emitted mass how much is API particles, i.e. , emitted dose pg;

[0162] Figure 13 shows images of the concentration of API substitute in the retained mass in preparation for spectrophotometer testing;

[0163] Figures 14a and 14b illustrate incoming airflow direction at different air-inlet piercer positions;

[0164] Figure 15a and 15b shows a bottom view of alternative inhaler apparatuses according to the present disclosure; Figures 16a to 16d show four alternative inhaler apparatuses where the air-inlet piercer positioning is selected to increase (from a) to d) as shown in the figures) the outward radial flow component;

[0165] Figures 17a to 17d shows top cross-sectional views of the alternative drug delivery device having the air-inlet piercer positions of Figures 16a to 16d respectively, and the respective tangential velocity within the blister illustrated by CFD;

[0166] Figures 18a to 18d show section views of the average tangential velocity map data for the alternative drug delivery device having the air-inlet piercer positions of Figures 16a to 16d respectively;

[0167] Figures 19a to 19d show sections of the maximum tangential velocity map data for the alternative drug delivery device having the air-inlet piercer positions of Figures 16a to 16d respectively;

[0168] Figure 20 shows a graph of emitted dose (%) based on different air-inlet piercer positions of Figure 16a to 16d;

[0169] Figure 21 shows a graph of emitted dose (%) based on the different air-inlet piercer positions of Figure 16a to 16d in comparison to the RS01-UHR device; and

[0170] Figures 22a to 22d shows images taken of the inhaler apparatus and the blister after the testing was carried out to collect the data provided for in Figure 20.

[0171] Specific Description

[0172] Figure 1 illustrates a drug-delivery apparatus according to an embodiment not within the scope of the claims. The drug-delivery apparatus comprises an inhaler apparatus 2 engaged with a blister 4 (in the drawing, part of the blister is cut away and the blister seal and the medicament contained in the blister are not shown, to show the structure of the inhaler apparatus more clearly).

[0173] The blister 4 comprises a blister pocket 6 surrounded by a flange and sealed by a blister seal. The outer edge of the blister pocket is circular, with a diameter between about 22 mm and about 23 mm, and an internal volume of approximately 1400 mm3. The cross-sectional shape of the blister pocket is parabolic. The angle between the flange and the outer edge of the blister pocket is moulded so that the strain in the material when the blister pocket is formed is less than 32%, meaning that the blister pocket can be cold formed from a laminate including a moisture-resistant aluminium layer.

[0174] As shown in Figure 1, the inhaler apparatus comprises an air outlet 12 extending from a blister-engaging plate 14. From the plate 14, the air outlet 12 terminates at an air-outlet piercer 16. The air-outlet piercer comprises a peripheral wall 18 terminating in a seal-cutting edge, and a cruciform-shaped central cutter terminating in a central piercing tip 20. Four raked cutting edges 22 extend from the central tip to the peripheral wall.

[0175] When this air-outlet piercer pierces the blister seal, it first penetrates or ruptures the seal at the piercing tip 20. As the piercer advances through the seal, the seal is cut by the four raked cutting edges to form four triangular seal portions or flaps between the cutting edges. As the piercer is pushed fully through the seal, the triangular seal portions abut an outer surface of the peripheral wall. The height of the peripheral wall 18 protruding from the blister-engaging plate 14 is equal to or slightly greater than the height of the triangular seal portions so that these seal portions do not occlude the air outlet.

[0176] Four air-inlet piercers 30 also extend from the blister-engaging plate 14, surrounding the airoutlet piercer 20. The air-inlet piercers are positioned at the same radius from the axis of the air-outlet piercer, and are spaced evenly around the outlet piercer. The air-outlet piercer is positioned centrally within the blister, and the central points of the air-inlet piercers are positioned halfway between the axis of the air-outlet piercer (and of the blister) and the peripheral edge of the blister pocket.

[0177] Each air-inlet piercer comprises two side walls 32, 34 converging at a piercing edge 36. At a downstream end of the piercer, a triangular air inlet 38 is defined between ends of the walls 32, 34 and an edge of the blister-engaging plate 14. The air inlet is at a large angle to the plate 14, of about 80°. An end of the piercing edge 36 adjacent to the air inlet 38 forms a piercing tip 40, and the piercing edge extends upstream away from the piercing tip 40 until it meets the blister-engaging plate 14 at its opposite end 42. The bases of the walls of the airinlet piercers, where they meet the blister-engaging plate, are curved, approximately along circumferential directions around the axis of the air outlet. The inlet piercers are curved around the central axis of the outlet so that, in use, the orientation of the air-inlet piercers induce tangential or circumferential airflow. The tangential, or circumferential, orientation of the airflow through the air inlets drives a rapid circumferential, cyclonic airflow within the blister, which carries the medicament with it.

[0178] Figures 2a and 2b illustrate an example embodiment of the inhaler apparatus of the present disclosure. The inhaler apparatus comprises a plate 102 for engaging a circular blister of the type illustrated in Figure 1. The plate 102 has a planar surface. The plate 102 is circular and is shaped to engage a circular blister. The plate 102 comprises an air-outlet piercer 104 for piercing an air outlet through a seal of the blister. Once the plate engages the circular blister, the air-outlet piercer 104 is positioned axially in the centre of the blister. As shown in Figure 2a, the air-outlet piercer 104 is axially positioned with respect to the plate 102. In other words, the central axis of the plate 102 and the air-outlet piercer 104 are the same. The air-outlet piercer 104 extends from the plate 102. The air-outlet piercer 104 comprises an air outlet and terminates with an outlet piercing tip. The air-outlet piercer 104 comprises a peripheral wall 106 terminating in a seal cutting edge, and a cruciform-shaped central cutter terminating in the outlet piercing tip. Four raked cutting edges 108 extend from the outlet piercing tip to the peripheral wall 106.

[0179] When this air-outlet piercer 104 pierces the blister seal, it first penetrates or ruptures the seal at the piercing tip. As the piercer advances through the seal, the seal is cut by the four raked cutting edges to form four triangular seal portions or flaps between the cutting edges. As the piercer is pushed fully through the seal, the triangular seal portions abut an outer surface of the peripheral wall. The height of the peripheral wall 106 protruding from the blister-engaging plate 102 is equal to or slightly greater than the height of the triangular seal portions so that these seal portions do not occlude the air outlet.

[0180] Four air-inlet piercers 110 also extend or protrude from the plate 102, as shown more clearly in Figure 2b, surrounding the air-outlet piercer 104. The air-inlet piercers 110 are positioned at the same radius from the axis of the air-outlet piercer 104. The air-inlet piercers 110 are for piercing an inlet opening through the seal of the blister.

[0181] Each air-inlet piercer 110 comprises an air-inlet opening 112. The air-inlet opening 112 is the opening through which air enters the blister from the air-inlet piercer. Each air-inlet piercer 110 comprises a side wall 114 and a foil deflecting wall 116. The edges of the air-inlet opening 112 are defined by the side wall 112, the foil deflecting wall 116, and the plate 102.

[0182] As shown more clearly in Figure 3, the inlet-piercer side wall 114 is substantially perpendicular to the plate 102. In other words, the side wall 114 projects vertically out of the plate 102. The foil deflecting wall 116 is for deflecting the seal when the air-inlet piercer 110 is being pushed through the seal.

[0183] A first, downstream, end of the side wall 114 forms a piercing edge. As such, the piercing edge is substantially perpendicular with respect to the plate 102, or vertical. A first end of the piercing edge ( the end furthest from the plate 102) and a first end of the foil deflecting wall 116 meet to form a piercing tip 120. The piercing tip 120 is configured to pierce an inlet opening through the foil seal of the blister. Both the side wall 114 and the foil deflecting wall 116 are planar and triangular in shape. As shown in Figure 3, the side wall 114 tapers from the first end of the side wall 114, i.e., the piercing edge, to the second end of the side wall 114. In other words, the side wall 114 increases in height with respect to the plate 104 towards the piercing tip. The foil deflecting wall 116 tapers from the second end of the foil deflecting wall 120 to the piercing tip 120. The second end of the foil deflecting wall 120 being the point of the wall 120 that meets the plate 102. In other words, the foil deflecting wall 116 narrows towards the piercing tip 120. The foil deflecting wall 120 slopes upwardly toward the piercing tip 120, this advantageously provides a streamlined profile and also provides a smooth cut and insertion movement of the air-inlet piercer 110 through the seal and into the blister.

[0184] The first side of the foil deflecting wall 116 an the side wall 114 meet to form a first cutting edge 118. The second side of the foil deflecting wall 118 forms a second cutting edge 122 along one side of the air-inlet opening 112. The first cutting edge 118 and the second cutting edge 122 meet at the piercing tip 120, and form an acute angle therebetween. The angle between the two cutting edges 118, 122 is between around 20 to 45 degrees. The second cutting edge 122 runs from the piercing tip 120 to the second end of the foil deflecting wall 116 where the foil deflecting wall 115 meets the plate 102. Both the first cutting edge 118 and the second cutting edge 122 are straight, so that they are configured to cut a straight line in the seal of the blister. As a result, when each air-inlet piercer 110 is in contact with the seal and pushed through, the piercing tip 120 pierces or punctures the seal, and the two cutting edges 118, 122 cut a triangular flap or seal portion in the seal of the blister. The triangular flap or seal portion is then deflected by the foil-deflecting wall 116, such that it does not occlude the air-inlet opening 112 or the air-outlet opening 104. In particular, the triangular flap is deflected such that it lies flat against the foil deflecting wall, and remains connected to the blister seal along one side of the flap. Advantageously, this reduces resistance to airflow in the blister in use. In comparison to the alternative embodiment of Figure 1, for example, the air-inlet piercer 110 is shaped such that when the seal is pierced I cut, the piercer cuts only a single flap of foil which is deflected by the foil deflecting wall. In the embodiment of Figure 1 by contrast, each air-inlet piercer typically deflects two flaps of foil into the blister, as the sloping walls either side of the cutting edge each create a flap of foil.

[0185] As discussed above, each air-inlet piercer 110 comprises the air-inlet opening 112 for directing air into the blister when air is drawn through the air outlet. The air-inlet opening 112 is defined by the side wall 112, the foil deflecting wall 116, and the plate 102. As shown in Figure 4, the air-inlet piercer 110 is oriented and positioned such that the airinlet opening 112 lies on a plane substantially perpendicular to the plate 102 and at an angle a of between about 75 to 85 degrees from a plane (plane Y-Y) substantially perpendicular to the plate and extending between a centre of the air-outlet piercer 104 and the piercing tip 120. This angle a introduces an outward radial flow component into the air leaving the airinlet opening 110. This advantageously directs the airflow towards the edge of the blister. The present inventors have appreciated that a combination of tangential flow and an outward radial flow, which would be provided by the orientation shown in Figure 4, reduces airflow resistance and also reduces the swirl number. In particular, in comparison to the known prior art, and also to alternative designs such as that shown in Figure 1 , whereby the air-inlet opening is orientated to induce tangential or circumferential flow only. The skilled person will appreciate that alternative angles a, between 45 to 135 degrees may also provide the desired effects. As also shown in Figure 4, the side wall of the air-inlet piercer lies on plane and at an angle p of between about 65 to 75 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip.

[0186] Increased Swirl Number

[0187] As shown in Figure 5, the vertical inlet-piercer side wall 114 lies on a side wall plane (plane Z-Z) orthogonal to both a radial plane (plane Y-Y) that passes through a central axis of the air-outlet piercer 104, and the plate 102. In the example embodiment of Figure 5, the air-inlet piercer is respectively positioned on the plate 102 such that the side wall plane (Z-Z) is at a distance (A) of about 35% to about 40% of the radius of the blister from the central axis. Further, in the example embodiment of Figure 5, the plate 102 is for engaging a circular blister with a diameter of about 22.5 mm. Therefore, each air-inlet piercer 110 is respectively positioned on the plate 102 such that the side wall plane (Z-Z) is at a distance (A) of about 4 mm to 4.5 mm from the central axis of the air-outlet piercer 104. However, the skilled person will appreciate that distance A can be between about 30% and 75% of the radius of the blister from the central axis of the air-outlet piercer 104. In this manner, distance A, may be between about 4 mm to 8 mm.

[0188] Experimental data when powdered medicament comprises API and carrier.

[0189] Figures 6a to 6d show a cross sectional top view of a drug delivery device comprising an inhaler apparatus and a blister. The flow fields of Figures 6a to 6d were simulated following a computational fluid dynamics (CFD) approach. The experimental setup shown in Figure 6 was used to investigate the effects of changing the distance between the side wall plane (Z-Z) and the central axis of the air-outlet piercer on the tangential velocity of the airflow and therefore the powdered medicament within the blister, when the powdered medicament comprises an API and a carrier. The experimental data relates to a powdered medicament comprising API and carrier, however, the skilled person would appreciate the same positioning can be used when the powdered medicament comprises API only.

[0190] In Figure 6a, the side wall plane is at a distance of about 35% to about 45% of the radius of the blister from the central axis. Specifically, the side wall plane is at a distance of about 4.3 mm from the central axis of the outlet 104, the diameter of the blister being about 22.5 mm.

[0191] In Figure 6b, the side wall plane is at a distance of about 40% to about 50% of the radius of the blister from the central axis of the outlet 104. Specifically, the side wall plane is at a distance of about 5.1 mm from the central axis of the outlet 104, the diameter of the blister being about 22.5 mm.

[0192] In Figure 6c, the side wall plane is at a distance of about 45% to about 55% of the radius of the blister from the central axis. Specifically, the side wall plane is at a distance of about 5.9 mm from the central axis of the outlet 104, the diameter of the blister being about 22.5 mm.

[0193] In Figure 6d, the side wall plane is at a distance of about 55% to about 65% of the radius of the blister from the central axis of the outlet 104. Specifically, the side wall plane is at a distance of about 6.7 mm from the central axis of the outlet 104, the diameter of the blister being about 22.5 mm.

[0194] As can be seen from the computational fluid dynamic (CFD) models of Figures 6a to 6d, as the distance between the side wall plane and the central axis of the outlet 104 increases, the tangential velocity towards the edge of the blister increases. The darker regions indicating higher tangential velocity than the lighter regions. This increase in tangential velocity towards the edge of the blister results in an increased swirl number. The present inventors have appreciated that this is particularly advantageous when the powdered medicament is carrier based. This is because by increasing the swirl number, increased deagglomeration of the powdered medicament comprising API and carrier can be achieved. Increased deagglomeration is desirable because in order to provide an effective dose for inhalation by the user, it is necessary to separate finer and smaller API particles from the carrier such that those finer and smaller API particles are free to be preferentially drawn through the outlet for inhalation by the user. Further, this results in the carriers particles being retained in the blister, which is advantageous because if the carrier particles were also drawn through the outlet, as seen with prior art devices, this would dilute the dose and can also have negative effects on the patient, such as resulting in excessive coughing and increased mouth and throat deposition.

[0195] The present inventors have appreciated that, when the powdered medicament comprises an API and a carrier, it is particularly advantageous to position each air-inlet piercer 110 such that the side wall plane (Z-Z) is at a distance of between about 45% to 55% of the radius of the blister from the central axis of the outlet 104, as shown in Figure 6c and 6d.

[0196] However, the inventors found that, surprisingly and counterintuitively, the most effective classification of a powdered medicament comprising an API and a carrier is provided when each air-inlet piercer 110 is positioned such that the side wall plane is at a distance of between about 50% to 55% of the radius of the blister from the central axis of the outlet 104, as shown in Figure 6c. This goes against classic cyclone chamber design, in which it is usually optimal to place the tangential air inlets as far out as possible, to maximise the swirl number. This is because, the positioning of the air-inlet piercer 110, as shown in Figure 6c, provides an increased swirl number while also providing more consistent and uniform airflow in comparison to that shown by the air-inlet piercer 110 positioning in Figure 6d, where weak spots occur that may can make the flow inconsistent. A more consistent flow advantageously conserves energy and as a result provides more efficient deagglomeration and as such more efficient evacuation and delivery of the drug to the user. It is also possible that the air-inlets 110 themselves are in the way of the path of the recirculating carrier particles when they are in the outermost position, as shown in Figure 6d. The carrier particles are likely to experience a higher number of collisions with the air-inlets 110 in the outmost position, and therefore have a higher chance of escaping from the blister, rather than being classified and retained.

[0197] Figures 7a to 7d are section views that illustrate the average tangential velocity in a blister. The air-inlet piercers are not shown due to the section view, however, Figures 7a and 7d conform to the respective air-inlet positioning shown in Figure 6a to 6d.The experimental setup shown in Figures 7a to 7d was used to investigate the effects of changing the distance between the side wall plane (Z-Z) and the central axis of the outlet 104 on the average tangential velocity of the airflow within the blister.

[0198] Figure 7a illustrates the average tangential velocity within the blister when the air-inlet piercer 110 is inbound i.e., closest to the central axis of the outlet 104. Whereas, Figure 7d illustrates the average tangential velocity within the blister when the air-inlet piercer 110 is outbound i.e., furthest away from the central axis of the outlet 104.

[0199] As illustrated, there is a higher outbound tangential velocity in the CFD models of Figures 7c and 7d, compared to that of Figures 7a and 7b. Therefore, when the air-inlet piercer 110 is positioned further away from the central axis of the outlet 104, as shown in Figures 6c and 6d, a higher swirl number at the outer edge of the blister is provided. Advantageously, this provides more effective deagglomeration as the medicament particles collide with one another and the wall of the blister. In addition, it can be seen that close to the central axis of the blister, the free swirl is stronger in Figures 7c and 7d as compared to Figures 7a and 7b; this can be seen by the closer contour lines and darker colour indicating higher average velocity. The increase in free swirl near the central axis of the blister improves the aerosolisation of the, smaller, API powder particles, and thus improves the evacuation of the API through the outlet 104.

[0200] Figure 8a to 8d are section views that illustrate the maximum tangential velocity within a blister. Figures 8a to 8d conform to the respective air-inlet positioning shown in Figure 6a to 6d. The experimental setup shown in Figures 8a to 8d was used to investigate the effects of changing the distance between the side wall plane (Z-Z) and the central axis of the outlet 104 on the maximum tangential velocity of the airflow I powdered medicament within the blister.

[0201] As can be seen from Figures 8a to 8d, the maximum tangential velocity is closer to the edge of the blister as the air-inlet piercer is moved further away from the central axis. This is advantageous as it provides more effective deagglomeration of the powdered medicament and prevents API particles being stuck at the edge of the blister.

[0202] Further, as can be seen in Figures 8c and 8d, the maximum velocity is increased around the air outlet 104 when the air-inlet piercer 110 is positioned as illustrated in Figures 6c and 6d. Therefore, the present inventors have also appreciated that the positioning of the air-inlet piercers 110 as depicted by Figures 6c and 6d may also provide more effective removal of the API powder from the blister through the air outlet 104. The present inventors carried out a number of tests in order to optimise the performance of the inhaler apparatus according to the present disclosure.

[0203] A first test was carried out to evaluate the effects of the air-inlet piercer 110 position as shown in Figures 6a to 6d on retention efficiency of the carrier when the powdered medicament comprises both API and carrier. In particular, a comparison was made of the air-inlet piercer 110 position to the mass retention of carrier within the blister (%) after inhalation, as seen in Figure 9. The test was carried out using 100 mg of powdered medicament substitute having a similar particle size distribution to an API and carrier mixture. The substitute comprised a mixture of coarse lactose carrier particles, ranging from about 70 pm to about 230 pm; a smaller fraction of fine lactose, about 10 pm in diameter; a small percentage (-1.5%) of magnesium stearate; and 1% of API mimic, also referred to herein as API substitute, (about 3 pm in diameter). The coarse fraction was about 90% of the total mass, with the fine lactose, magnesium stearate and the API mimic making up the remaining 10% of the total mass.

[0204] Point a) on Figure 9 conforms to the mass retention of the carrier in the blister when the side wall plane is at a distance of 4.3 mm from the central axis of the outlet. As can be seen, this resulted in a mass retention in the blister of around 62.4% i.e. , around 62.4% of the initial fill mass is retained in the blister, which, as described below is formed of approximately 100% carrier.

[0205] Point b) on Figure 9 conforms to the mass retention of the carrier in the blister when the side wall plane is at a distance of 5.1 mm from the central axis of the outlet. As can be seen, this resulted in a mass retention in the blister of around 71.2%.

[0206] Point c) conforms to the mass retention of the carrier in the blister when the side wall plane is at a distance of 5.9 mm from the central axis of the outlet. As can be seen, this resulted in a mass retention in the blister of around 75.3%.

[0207] Point d) conforms to the mass retention of the carrier in the blister when the side wall plane is at a distance of 6.7 mm from the central axis of the outlet. As can be seen, this resulted in a mass retention in the blister of around 62.3%. In each case, despite the high retention rate of the powdered medicament, approximately 98% of the API substitute was aerosolised and evacuated from the blister. The results of the tests are summarised below in Table 1:

[0208] The present inventors carried out the same test on inhaler device RS01 ultra-high resistance (RS01-UHR). RS01-UHR is a standard inhaler apparatus currently used on the market for aerosolising API for delivery to a user and provides the most accurate comparison to the inhaler apparatus according to the present disclosure. The apparatus was filled with 100 mg of powdered medicament substitute having a particle size distribution equivalent to an API and carrier. The test was carried out at the equivalent pressure drop (4 kPa) and a similar flowrate (43 LPM) to the above described tests, and the retained mass in the blister was 40.3 mg, i.e., about 40% mass retention. However, about 350 pg of the API substitute was also retained (35% of filled), i.e. only 65% was emitted as a dose.

[0209] Consequently, it is clear that the inhaler apparatus as tested in Figure 9 and according to the present disclosure aims and succeeds at reducing the amount of carrier inhaled by the user, for a given dose of API, by increasing the amount of carrier retained in the blister.

[0210] This is further reaffirmed by a second measurement taken from the above described test carried out by the present inventors. The second measurement determined the effects of the air-inlet piercer position as shown in Figures 6a to 6d on the emitted active concentration, when the powdered medicament substitute comprised both API substitute and carrier. In other words, evaluating how much of the emitted dose is API in comparison to how much is carrier. As discussed previously, one of the aims of the present disclosure is to increase the concentration of API in the emitted dose.

[0211] Similarly to Figure 9, point a) on Figure 10 illustrates the emitted active concentration when the side wall plane is at a distance of 4.3 mm from the central axis of the outlet. As can be seen, this resulted in an emitted active concentration of around 2.62% (the original concentration being approximately 1%). This means in the test where 100 mg of powdered medicament substitute was placed within the blister before inhalation and 62.51 mg was retained after inhalation, of the 37.49 mg evacuated, 2.62% of this was API substitute. Therefore, about 1 mg is API. In comparison to known prior art, the user or patient is receiving much less carrier per dose of API. This is because, in order for the user to receive 1 mg of API in the RS01-UHR device, almost all of the carrier must be inhaled by the user. Therefore, even when the air-inlet piercers of the present disclosure are positioned in the position that induces the least swirl, the retention and the emitted dose concentration is still significantly improved in comparison to the known prior art.

[0212] Point b) of Figure 10 illustrates the emitted active concentration when the side wall plane is at a distance of 5.1 mm from the central axis of the outlet. As can be seen, this resulted in an emitted active concentration of around 3.4%.

[0213] Point c) illustrates the emitted active concentration when the side wall plane is at a distance of 5.9 mm from the central axis of the outlet. As can be seen, this resulted in an emitted active concentration of around 3.97%.

[0214] Point d) illustrates the emitted active concentration when the side wall plane is at a distance of 6.7 mm from the central axis of the outlet. As can be seen, this resulted in an emitted active concentration of around 2.6%.

[0215] Therefore, as can be seen from Figure 10 and the data obtained and as appreciated by the present inventors, the inhaler apparatus according to the present disclosure is surprisingly particularly advantageous when the side wall plane is at a distance of between about 45% to 55% of the radius of the blister from the central axis of the air-outlet piercer. Further, even more advantageously, when the when the side wall plane is at a distance of between about 49% to 53% of the radius of the blister from the central axis of the air-outlet piercer. This is because, the present inventors have appreciated that, even though the swirl number is not as high as it can be when the air-inlet piercers are positioned further away from the central axis, the uniform and controlled flow achieved at this distance in combination with the high swirl number results in more effective retention of the carrier while also allowing for effective evacuation of the API particles.

[0216] The present inventors also took this second measurement from the above described test carried out on the RS01-UHR to evaluated how much of the emitted dose is API in comparison to how much is carrier. This resulted in an emitted active concentration of around 1.09%. This means in the test where 100 mg of powdered medicament substitute was placed within the apparatus before inhalation and 40.32 mg was retained after inhalation, of the 59.68 mg evacuated, 1.09% of this was API substitute. This is considerably less than the emitted active concentration when using an inhaler apparatus according to the present disclosure, as shown in Figure 10.

[0217] To further illustrate the significant advantages and improvements achieved by the inhaler apparatus according to the present disclosure, Figure 11 is a bar chart that shows, for each air-inlet piercing position tested and the RS01-UHR, the percentage of the retained powdered medicament substitute mass (referred to as RM). Figure 11 also shows, for each air-inlet piercing position tested and the RS01-UHR, the proportion of API originally contained within the blister that was emitted during simulated inhalation (referred to as ED - “Emitted Dose”). As can be seen, the retained mass within the blister after simulated inhalation, is consistently considerably higher when using an inhaler apparatus according to the present disclosure, in comparison to RS01-UHR. This in combination with the percentage of API in the emitted dose being consistently significantly higher than that of RS01-UHR, further re-affirms that the inhaler apparatus according to the present disclosure results in more effective retention of the carrier while also allowing for effective evacuation of API particles.

[0218] In particular, it is clear that, of the apparatus tested, the apparatus represented as point c) is the most advantageous. This is because it achieves the highest retained mass while also providing a high emitted dose of API.

[0219] Figure 12 is a bar chart that shows, for each air-inlet piercing position and the RS01-UHR, the total emitted mass in mg (left axis) and of that total emitted mass how much is API particles, i.e., emitted dose in pg (right axis). As can be seen, the inhaler apparatus according to the present disclosure reduces the total emitted mass while also increasing the proportion of API particles in the emitted total mass. As above, it should be noted that the mass of API substitute in the initial fill mass was equivalent for both the RS01 and apparatus according to the present disclosure.

[0220] Figure 13 shows images representing the powered medicament substitute retained in the RS01-UHR device in comparison to the powered medicament substitute retained in the inhaler apparatus according to the present disclosure 1300. The retained powdered medicaments were dissolved in a solvent for use in a spectrophotometer to determine the relative concentration of API substitute which includes a “blue” dye. As can be seen, the retained powdered medicament in the RS01-UHR device comprises a higher concentration of API substitute than when using the inhaler apparatus according to the present disclosure 1300. The spectrophotometer was used to determine the concentration of API substitute in the retained mass.

[0221] Increased Radial Flow Component

[0222] Figures 14a and 14b illustrate the vector components of incoming airflow entering a blister (not shown) through the air-inlet openings. In the examples shown, the radial component of the incoming airflow is lower in the Figure 14a example as compared to the Figure 14b example. Increasing the radial component of the incoming airflow reduces Swirl Number, reduces classification and promotes a higher emitted dose.

[0223] Further, as shown in Figure 15a, the piercing tip 120 is at a distance (X) of 0 mm from the radial plane (Y-Y) i.e. , the piercing tip 120 intersects the radial plane Y-Y. Each air-inlet piercer 110 can be positioned respectively, on a first side B of the radial plane Y-Y or the second side C of the radial plane. This is shown in Figure 15b, whereby each air-inlet piercer 110 is positioned such that the piercing tip 120 is at a distance X of around 25% of the radius of the blister from the radial plane Y-Y on the second side C. When the piercing tip 120 is on the second side of the plane Y-Y, the radial plane intersects the air-inlet. The plate 102 of Figure 15a and 15b is for engaging a circular blister with a diameter of about 18.7 mm, however, the skilled person will appreciate the proportions can be applied to blisters with alternative diameters, for example between about 22 mm to 23 mm. Therefore, each air-inlet piercer 110 of Figure 15b is respectively positioned on the plate 102 such that the piercing tip 120 is at distance X of about 1 mm to about 2 mm from the radial plane Y-Y on the second side C. In other words, the distance is between around 10% to about 20% of the radius of the blister. However, the skilled person will appreciate that distance X can be up to about 50 % of the radius of the blister from the central axis of the air-outlet piercer 104. In this manner, distance X, in this example embodiment, may be up to about 5 mm to about 6 mm. As the air-inlet piercer 110 is positioned towards 50% of the radius of the blister on the second side of the radial plane the radial flow component of the airflow increases.

[0224] Advantageously, the present inventors have appreciated firstly that the position of each airinlet piercer 110 can adjust the type of airflow by increasing the tangential flow component and / or increasing the radial flow component of the flow regime. Secondly, that by increasing the outward radial flow component, the airflow resistance is reduced and the swirl number is also reduced. Figure 16a to 16d illustrates a range of different positions of the air-inlet piercers 110 which produce cyclonic airflows within a blister. Each of the different air-inlet piercer positions provides a different radial flow vector component. Thus, each of the different air-inlet piercer positions varies the properties of the swirling airflow established in the blister in use. As the position of the air-inlet piercer is changed from Figure 16a to 16d the radial flow component introduced is increased, which the present inventors have found and appreciated leads to significant advantages over the prior art, in particular, when the powdered medicament comprises API only. These advantages are evidenced I supported and discussed in more detail below.

[0225] Experimental Data when powdered medicament comprises API

[0226] The present inventors have appreciated that it is desirable to obtain the maximum dose of API out of the blister through the air-outlet for inhalation by the user. Therefore, the present inventors have devised, designed and tested the inhaler apparatus according to the present disclosure to provide an inhaler apparatus that draws an improved dose of API out of the blister and provides a more efficient airflow and as such more efficient delivery of the drug to the user or patient.

[0227] Figures 17a to 17d show a bottom cross-sectional view, adjacent the plate on which the airinlets 110 and air-outlet 104 are provided, of a drug delivery device comprising the inhaler apparatus and a blister.

[0228] The experimental setup shown in Figures 17a to 17d was used to investigate the effects of changing the position of the air-inlet piercer 110 as illustrated in Figures 16a to 16d respectively on the tangential airflow velocity. In particular, the experiment was conducted to show the effect of varying the distance between the second side C of the radial plane Y-Y and the piercing tip 120 of the air-inlet piercer 110, which the present inventors have found increases the radial flow component. CFD modelling was used to provide the flow field data.

[0229] In Figure 17a, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance (X) of 0 mm from the radial plane (Y-Y) i.e. , the piercing tip 120 intersects the radial plane Y- Y.

[0230] In Figure 17b, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 1.07mm from the radial plane. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 11.5% of the radius of the blister from a second side of the radial plane Y-Y.

[0231] In Figure 17c, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 2.29 mm from the radial plane. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 24.5% of the radius of the blister from a second side of the radial plane Y-Y.

[0232] Finally, in Figure 17d, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 3.87 from the radial plane Y-Y. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 41.4% of the radius of the blister from a second side of the radial plane.

[0233] The radial flow vector component is dependent on the position of each air-inlet piercer. It can be seen that the radial flow vector component is greater in the configuration of Figure 17d that that of Figure 17a for example. In other words, the radial vector component increases when the distance between the piercing tip and the second side of the radial plane Y-Y is greater. The skilled person will appreciate that the distances provided are examples with regards to a blister with 18.7 mm diameter. Alternative distances and blister sizes may also be provided.

[0234] The present inventors have appreciated that introducing and increasing the radial flow vector component to the airflow is particularly advantageous when the powdered medicament comprises API only. This is because adding a radial flow component to the airflow reduces the swirl number and as such advantageously reduces the likelihood of agglomeration and accumulation towards the edge of the blister, allowing for better particle dispersion, separation and aerosolisation.

[0235] As the distance between the piercing tip and the second side of the radial plane increases, the addition of the radial flow component ensures that the airflow is directed towards the edge of the blister. The addition of the radial flow component increases the average tangential velocity, and also the scouring power, at the edge of the blister. This advantageously, improves the scouring effect of the airflow and prevents the API particles from being stuck at the edge of the blister. In other words, an increase in the radial flow component improves the edge clearance. Consequently, the API particles are free to be drawn from the outer edge of the blister towards the outlet. However, the inventors found that, surprisingly, when each air-inlet piercer is positioned such that the distance between the piercing tip and the second side of the radial plane is between about 2 mm (as shown in Figure 17c) and about 4 mm (as shown in Figure 17d), better evacuation and as such a better dose of fine API particles is provided. The skilled person will appreciate that about 2 mm to about 4 mm applies to the blister of the experimental set up which has a diameter of about 18.7 mm. Therefore, for blisters with alternative diameters, the inventors have appreciated that, when the distance between the piercing tip and the second side of the radial plane is between about 20% to 40% of the radius of the blister, the advantageous effects of better evacuation and an improved dose of fine API particles are also achieved. This is shown in more detail in Figure 20 and discussed below.

[0236] The configuration as illustrated in Figure 17d is also advantageous in that it increases the radial flow component and as such increases the tangential velocity at the edge of the blister, the inventors have found that surprisingly a middle ground between the configuration as illustrated in Figure 17c and Figure 17d is preferable, because it provides a more uniform and controlled flow pattern or regime. This can be seen more clearly in Figure 17d, whereby there are weak spots which can interrupt the flow. Uniform flow is advantageous because it facilitates a more even distribution of particles and higher separation efficiency, which in turn, provides more efficient evacuation of the API.

[0237] Figures 18a to 18d are section views that illustrate the average tangential velocity within a blister. Figures 18a to 18d conform to the respective air-inlet 110 positioning shown in Figures 16a to 16d and Figures 17a to 17d respectively. The experimental setup shown in Figures 18 was used to investigate the effects of changing the distance between the piercing tip 120 and the second side of the radial plane on the average tangential velocity of the airflow / powdered medicament within the blister.

[0238] Figure 18a illustrates the average tangential velocity within the blister when each air-inlet piercer is positioned such that the piercing tip lies on the radial plane. Figure 18d conforms to Figure 17d, where each air-inlet piercer is positioned such that the piercing tip is at a distance of about 4 mm from the second side of the radial plane. As shown, when the distance between the second side of the radial plane and the piercing tip 120 increases, the average tangential velocity is higher near the edge of the blister. This is advantageous as it ensures the necessary clearance is achieved at the edge of the blister so that all the API particles are free to be drawn into the outlet 104 and as such maximum mass output of the API particles in achieved. Figures 19a to 19d show section views that illustrate the maximum tangential velocity within a blister. Figures 19a to 19d conform to the respective air-inlet position shown in Figures 16a to 16d and 17a to 17d. The experimental setup shown in Figures 19a to 19d was used to investigate the effects of changing the distance between the piercing tip and the second side of the radial plane on the maximum tangential velocity of the airflow I powdered medicament within the blister. As can be seen, the maximum tangential velocity is achieved at the edge of the blister, when the air-inlet piercers 110 are positioned at a distance of between about 20 to 40% of the radius of the blister from the second side of the radial plane.

[0239] The present inventors carried out a number of tests in order to optimise the performance of the inhaler apparatus according to the present disclosure. In particular, when the inhaler apparatus is for aerosolising a powdered medicament comprising API only contained within a blister.

[0240] The main test carried out was evaluating the effects of the air-inlet piercer position as shown in Figures 16a to 16d and Figures 17a to 17d, when the powdered medicament comprises API only. In particular, comparing how the emitted dose (%) varies dependent on the position of the air-inlet piercers, as seen in Figure 20. Further how this data compares to a device of the prior art. The test was carried out using 50 mg of powdered medicament substitute comprising API substitute only. The powdered medicament remaining after inhalation was recorded and as such the emitted dose per 50 mg was recorded as a percentage.

[0241] Point a) on Figure 20 is the emitted dose when the piercing tip lies on or intersects the radial plane (Y-Y). In other words, the distance between the radial plane and the piercing tip is 0 mm. In the inhaler apparatus tested for point a) the air-inlet opening lies on a plane substantially perpendicular to the plate 102 and at an angle a of about 70 degrees from a plane substantially perpendicular to the plate 102 and extending between a centre of the airoutlet piercer 104 and the piercing tip 120. As can be seen, at point a), the emitted dose is 89.8%. Therefore, 89.8% of the API substitute in the blister is evacuated.

[0242] Point b) on Figure 20 is the emitted dose when the piercing tip is at a distance of about 1.07 mm from the second side of the radial plane. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 11.5% of the radius of the blister from a second side of the radial plane Y-Y. The air-inlet opening lies on a plane substantially perpendicular to the plate and at an angle of about a 80 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip. As can be seen, at point b) the emitted dose is 92.4%. Therefore, 92.4% of the API substitute in the blister is evacuated.

[0243] Point c) on Figure 20 is the emitted dose when the piercing tip is at a distance of about 2.29 mm from the second side of the radial plane. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 24.5% of the radius of the blister from a second side of the radial plane Y-Y. The air-inlet opening lies on a plane substantially perpendicular to the plate and at an angle of about a 95 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip. As can be seen, at point c) the emitted dose is 95.4%.

[0244] Therefore, 95.4% of the API substitute in the blister is evacuated.

[0245] Point d) on Figure 20 is the emitted dose when the piercing tip is at a distance of about 3.87 mm from the second side of the radial plane. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 41.4% of the radius of the blister from a second side of the radial plane. The air-inlet opening lies on a plane substantially perpendicular to the plate and at an angle of about a 105 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip. As can be seen, at point d) the emitted dose is 96%. Therefore, 96% of the API substitute in the blister is evacuated.

[0246] The present inventors carried out the same test on inhaler device RS01 ultra-high resistance (RS01-UHR). When the apparatus was filled with 50 mg of powdered medicament comprising API only, the average emitted dose was 45.5% after a first evacuation and 54.5% after a second evacuation (the instructions for standard use indicate that the user inhales twice if there appears to be powder remaining in the capsule). This means, even after a second evacuation, only 54.5% of the API would be delivered to the user because the RS01- UHR device does not perform any classification of the powdered medicament. Further, the emitted dose was highly variable, with a mean of 22.7 mg (45%) upon first inhalation, rising to 27.2 mg (55%) upon the second inhalation (up to two inhalations are recommended in the user instructions for the RS01). Therefore, it is clear that the inhaler apparatus according to the present disclosure advantageously increases the emitted dose.

[0247] Figure 21 shows a comparison of the inhaler apparatus according to the present disclosure and the RS01-UHR. Firstly, as can be seen the emitted dose is significantly lower than that of any of the inhaler apparatus with the air-inlet piercers positioned as shown in Figures 16a to 16d and Figures 17a to 17d. Therefore, with the same effort the user of an inhaler apparatus according to the present disclosure can obtain a greater dose of API in comparison to using the RS01-UHR device. Secondly, the standard deviation of around 25% for the data collected for RS01-UHR is undesirable, in particular, for a medical device. This is because, this means there is no consistency in the amount of API the user receives each time they inhale and as such the dose received by the user cannot be accurately monitored.

[0248] As can be seen from Figure 20 and as appreciated by the present inventors, the emitted dose increases as the distance from the second side of the radial plane increases. This is because the radial flow component is increased which in turn directs the flow from the airinlet opening towards the outer edge of the blister. This improves the edge clearance by ensuring that the maximum amount of API is cleared from the edge of the blister and as such free to be drawn into the air-outlet.

[0249] Figures 22a to 22d shows images taken of the inhaler apparatus and the blister after the testing was carried out to collect the data provided for in Figure 20. These images have been put next to the CFD data of Figures 17a to 17d, 18a to 18d and 19a to 19d respectively.

[0250] Figure 22a shows the API substitute dispersion after inhalation in the inhaler apparatus and the blister, when the air-inlet piercers are positioned such that the distance between the radial plane and the piercing tip is 0 mm. As can be seen, although the emitted dose is 89.8%, which is still an improvement over the known prior art devices, the API substitute which remains in the blister is concentrated around the edge and in the middle of the blister, in comparison to the API distribution in Figures 22b to 22d. This is because less energy is directed towards the edge of the blister and instead a relatively more powerful vortex is formed near the central axis of the blister, with a relatively larger section of lower average velocity in a region between the centre and the edge.

[0251] Figure 22b shows the API substitute dispersion after inhalation in the inhaler apparatus and the blister, when the air-inlet piercers are positioned such that the piercing tip is at a distance of about 1.07 mm from the second side of the radial plane. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 11.5% of the radius of the blister from a second side of the radial plane Y-Y. As can be seen, the emitted dose is 92.4% but the API substitute which remains in the blister is concentrated around the edge and in the middle of the blister. Figure 22c shows the API dispersion after inhalation in the inhaler apparatus and the blister, when the air-inlet piercers are positioned such that the piercing tip is at a distance of about 2.29 mm from the second side of the radial plane. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 24.5% of the radius of the blister from a second side of the radial plane Y-Y. As can be seen the edge clearance improves around this position. This is because of the increase in the radial component of the airflow which acts to scour the edge of the blister, but with sufficient and consistent tangential velocity to ensure maximum aerosolisation of the API substitute.

[0252] Figure 22d shows the API dispersion after inhalation in the inhaler apparatus and the blister, when the air-inlet piercers are positioned such that the piercing tip is at a distance of about 3.87 mm from the second side of the radial plane. In other words, the air-inlet piercer is positioned such that the piercing tip 120 is at a distance of about 41.4% of the radius of the blister from a second side of the radial plane. The less uniform flow velocity and lack of swirl results in additional API substitute remaining adjacent the air-inlets. Despite the improved scouring of the edge of the blister, the air-inlet position shown in Figure 22c was found to be better.

[0253] The skilled person will appreciate that the specific dimensions disclosed herein reference the specific apparatus used to obtain the enclosed test data. However, alternative dimensions are also suitable.

[0254] Preferred Aspects - Inhaler Apparatus

[0255] Embodiments of the disclosure can be described with reference to the following numbered clauses, with additional features laid out in the dependent clauses:

[0256] Clause 1: An inhaler apparatus for aerosolising a powdered medicament contained within a circular blister, the apparatus comprising: a plate for engaging a circular blister, the plate comprising: an air-outlet piercer for piercing an air outlet through a seal of the blister, the air-outlet piercer being axially positioned in the blister; and a plurality of air-inlet piercers surrounding the air-outlet piercer, each for piercing an inlet opening through the seal, each air-inlet piercer comprising: an air-inlet opening; a side wall substantially perpendicular to the plate; and a foil deflecting wall, wherein a first side of the foil deflecting wall and the side wall meet to form a cutting edge.

[0257] Clause 2: An inhaler apparatus according to clause 1, wherein each air-inlet piercer comprises a piercing tip for piercing an inlet opening through the seal and an air-inlet opening, for directing air into the blister when air is drawn through the air outlet, wherein the piercing tip is located at a first end of the side wall.

[0258] Clause 3: An inhaler apparatus according to clause 2, wherein the air-inlet opening lies on a plane substantially perpendicular to the plate and at an angle of between about 45 to 135 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip.

[0259] Clause 4: An inhaler apparatus according to clause 3, wherein the air-inlet opening is positioned to introduce a radial flow component to air passing through the air-inlet piercer.

[0260] Clause 5: An inhaler apparatus according to claim 2 or 3, wherein the air-inlet opening is positioned to induce a tangential flow component to air passing through the air-inlet piercer.

[0261] Clause 6: An inhaler apparatus according to any of clause 3 to 5, wherein the air-inlet opening lies on the plane substantially perpendicular to the plate and at an angle of between about 45 to 90 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip.

[0262] Clause 7: An inhaler apparatus according to any preceding clause, wherein the side wall lies on a side wall plane orthogonal to both a radial plane, wherein the radial plane passes through a central axis of the air-outlet piercer, and the plate.

[0263] Clause 8: An inhaler apparatus according to clause 7, wherein each air-inlet piercer is respectively positioned on the plate such that the side wall plane is at a distance of between about 25% and about 75% of the radius of the blister from the central axis of the air-outlet piercer and / or such that the piercing tip is at a distance of up to about 50% of the radius of the blister from a first side of the radial plane or at a distance of up to about 50% of the radius of the blister from a second side of the radial plane.

[0264] Clause 9: An inhaler apparatus according to any preceding clause, wherein the first end of the side wall forms a piercing edge. Clause 10: An inhaler apparatus according to clause 9, wherein a first end of the piercing edge and a first end of the foil deflecting wall meet to form the piercing tip for piercing an inlet opening through the seal.

[0265] Clause 11: An inhaler apparatus according to any preceding clause, wherein the foil deflecting wall is a triangular wall.

[0266] Clause 12: An inhaler apparatus according to any preceding clause, wherein the foil deflecting wall tapers from a second end of the foil deflecting wall to the piercing tip, wherein the second end of the foil deflecting wall meets the plate.

[0267] Clause 13: An inhaler apparatus according to any preceding clause, wherein the side wall is a triangular wall.

[0268] Clause 14: An inhaler apparatus according to any preceding clause, wherein the side wall tapers from the piercing edge to a second end of the side wall.

[0269] Clause 15: An inhaler apparatus according to any preceding clause, wherein the cutting edge is configured to cut a straight line in the seal of the blister.

[0270] Clause 16: An inhaler apparatus according to any preceding clause, wherein each air-inlet piercer is shaped so as to cut the seal of the blister to form a single flap in the seal of the blister.

[0271] Clause 17: An inhaler apparatus according to any preceding clause, wherein the air-inlet opening is defined by the side wall, the foil deflecting wall and the plate.

[0272] Clause 18: An inhaler apparatus according to any preceding clause, wherein a second side of the foil-deflecting wall forms a second cutting edge.

[0273] Clause 19: An inhaler apparatus according to clause 18, wherein the second cutting edge runs from the piercing tip to the second end of the foil-deflecting wall at where the second end of the foil deflecting wall meets the plate.

[0274] Clause 20: An inhaler apparatus according to clause 18 or 19, wherein the cutting edge and the second cutting edge meet at the piercing tip, and form an acute angle therebetween.

[0275] Clause 21: An inhaler apparatus according to any preceding clause, in which the piercer is configured to cut a triangular flap in the seal of the blister, such that the triangular flap is deflected by the foil-deflecting wall.

[0276] Clause 22: An inhaler apparatus according to any preceding clause, wherein the plurality of air-inlet piercers are positioned at the same radius from the axis of the air-outlet piercer. Clause 23: An inhaler apparatus according to any preceding clause, wherein the plate comprises four air-inlet piercers.

[0277] Clause 24: An inhaler apparatus according to any preceding clause, wherein the air-inlet piercers are arranged symmetrically around the air-outlet piercer.

[0278] Clause 25: A drug delivery device for aerosolising a powdered medicament contained within a circular blister, the device comprising: a blister containing the medicament, and comprising a circular blister pocket sealed by a pierceable seal; and an inhaler apparatus according to any preceding clause.

[0279] Clause 26: A drug delivery device according to clause 25, in which the dimensions of the outlet and the inlets are selected so that the rate of airflow inhaled by a user through the inhaler is limited by airflow through the outlet.

[0280] Clause 27: A drug delivery device according to clause 25 or 26, in which the depth of the blister is greater than 1.2 times the distance which the air-outlet piercer extends into the blister, and is preferably 1.5 or 2 or 3 times the distance which the air-outlet piercer extends into the blister.

[0281] Clause 28: A drug-delivery device according to any of clauses 25 to 27, in which the blister pocket has a parabolic cross section.

[0282] Clause 29: A drug-delivery device according to any of claim 25 to 28, in which all of the air inhaled by a user passes through the blister.

[0283] Preferred Aspects - Orientation of air-inlet opening

[0284] Clause 30. An inhaler apparatus for aerosolising a powdered medicament contained within a circular blister, the apparatus comprising: a plate for engaging a circular blister comprising: an air-outlet piercer for piercing an air outlet through a seal of the blister, the air-outlet piercer being axially positioned in the blister; and a plurality of air-inlet piercers surrounding the air-outlet piercer, each air-inlet piercer comprising: a piercing tip for piercing an inlet opening through the seal; and an air-inlet opening, facing away from the air-outlet piercer, for directing air into the blister when air is drawn through the air outlet, wherein the air-inlet opening lies on a plane substantially perpendicular to the plate and at an angle of between about 45 to 135 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip.

[0285] Clause 31. An inhaler apparatus according to clause 30, wherein the air-inlet opening is positioned to introduce a radial flow component to air passing through the air-inlet piercer.

[0286] Clause 32. An inhaler apparatus according to clause 30 or 31 , wherein the air-inlet opening is positioned to induce a tangential flow component to air passing through the air-inlet piercer.

[0287] Clause 33. An inhaler apparatus according to any of clauses 30 to 32, wherein the air-inlet opening lies on the plane substantially perpendicular to the plate and at an angle of between about 45 to 90 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip.

[0288] Clause 34. An inhaler apparatus according to any of clauses 30 to 33, wherein the air-inlet opening in triangular in shape.

[0289] Clause 35. An inhaler apparatus according to any of clauses 30 to 34, wherein each air-inlet piercer comprises a side wall substantially perpendicular to the plate.

[0290] Clause 36. An inhaler apparatus according to clause 35, wherein each air-inlet piercer further comprises a foil deflecting wall, the foil deflecting wall and the side wall meet to form a cutting edge.

[0291] Clause 37. An inhaler apparatus according to clause 36, wherein the air-inlet opening is defined by the side wall, the foil deflecting wall and the plate.

[0292] Clause 38. A drug delivery device for aerosolising a powdered medicament contained within a circular blister, the device comprising: a blister containing the medicament, and comprising a circular blister pocket sealed by a pierceable seal; and an inhaler apparatus according to any preceding clause.

[0293] Preferred Aspects - Relative position of Air Inlet Piercers Clause 39. An inhaler apparatus for aerosolising a powdered medicament contained within a circular blister, the apparatus comprising: a plate for engaging a circular blister comprising: an air-outlet piercer for piercing an air outlet through a seal of the blister, the air-outlet piercer being axially positioned in the blister; and a plurality of air-inlet piercers surrounding the air-outlet piercer, each air-inlet piercer comprising: a side wall, facing away from the air-outlet piercer, wherein the side wall lies on a side wall plane orthogonal to both a radial plane, wherein the radial plane passes through a central axis of the air-outlet piercer, and the plate; and a piercing tip for piercing an inlet opening through the seal of the blister, wherein the piercing tip is located at a first end of the side wall, wherein each air-inlet piercer is respectively positioned on the plate such that the side wall plane is at a distance of between about 25% and about 75% of the radius of the blister from the central axis of the air-outlet piercer and / or such that the piercing tip is at a distance of up to about 50% of the radius of the blister from a first side of the radial plane or at a distance of up to about 50% of the radius of the blister from a second side of the radial plane.

[0294] Clause 40. An inhaler apparatus according to clause 39, wherein the piercing tip is positioned such that the piercing tip is at a distance of up to 50% of the radius of the blister from the second side of the radial plane so as to introduce a radial flow component to air passing through the air-inlet piercer.

[0295] Clause 41. An inhaler apparatus according to clause 40, wherein each air-inlet piercer is positioned so as to introduce both a tangential flow component and the radial flow component to air passing through the air-inlet piercer.

[0296] Clause 42. An inhaler apparatus according to any of clauses 39 to 41, wherein each air-inlet piercer is respectively positioned on the plate such that the piercing tip is at a distance of between about 20% to 50% of the radius of the blister from the second side of the radial plane.

[0297] Clause 43. An inhaler apparatus according to any of clauses 39 to 42, wherein each air-inlet piercer is respectively positioned on the plate such that the side wall plane is at a distance of between about 40% and about 60% of the radius of the blister from the central axis of the air-outlet piercer.

[0298] Clause 44. An inhaler apparatus according to any of clauses 39 to 43, wherein each air-inlet piercer comprises an air-inlet opening, for directing air into the blister when air is drawn through the air outlet.

[0299] Clause 45. An inhaler apparatus according to clause 44, wherein the air-inlet opening lies on a plane substantially perpendicular to the plate and at an angle of between about 25 to 60 degrees from the side wall plane.

[0300] Clause 46. An inhaler apparatus according to any of clause 39 to 45, wherein the plate comprises four air-inlet piercers.

[0301] Clauses 47. An inhaler apparatus according to any of clauses 39 to 46, wherein the air-inlet piercers are arranged symmetrically around the air-outlet piercer.

[0302] Clauses 48. A drug delivery device for aerosolising a powdered medicament contained within a circular blister, the device comprising: a blister containing the medicament, and comprising a circular blister pocket sealed by a pierceable seal; and an inhaler apparatus according to any preceding clause.

Claims

Claims1. An inhaler apparatus for aerosolising a powdered medicament contained within a circular blister, the apparatus comprising: a plate for engaging a circular blister, the plate comprising: an air-outlet piercer for piercing an air outlet through a seal of the blister, the air-outlet piercer being axially positioned in the blister; and a plurality of air-inlet piercers surrounding the air-outlet piercer, each for piercing an inlet opening through the seal, each air-inlet piercer comprising: an air-inlet opening; a side wall substantially perpendicular to the plate; and a foil deflecting wall, wherein a first side of the foil deflecting wall and the side wall meet to form a cutting edge.

2. An inhaler apparatus according to claim 1 , wherein a first end of the side wall forms a piercing edge.

3. An inhaler apparatus according to claim 2, wherein a first end of the piercing edge and a first end of the foil deflecting wall meet to form a piercing tip for piercing an inlet opening through the seal.

4. An inhaler apparatus according to claim 3, wherein the foil deflecting wall is a triangular wall.

5. An inhaler apparatus according to claim 4, wherein the foil deflecting wall tapers from a second end of the foil deflecting wall to the piercing tip, wherein the second end of the foil deflecting wall meets the plate.

6. An inhaler apparatus according to any of claims 2 to 5, wherein the side wall is a triangular wall.

7. An inhaler apparatus according to claim 6, wherein the side wall tapers from the piercing edge to a second end of the side wall.

8. An inhaler apparatus according to any preceding claim, wherein the angle between the side wall and a plane of the foil deflecting wall is between around 80 to 120 degrees.

9. An inhaler apparatus according to any preceding claim, wherein the cutting edge is configured to cut a straight line in the seal of the blister.

10. An inhaler apparatus according to any preceding claim, wherein each air-inlet piercer is shaped so as to cut the seal of the blister to form a single flap in the seal of the blister.

11. An inhaler apparatus according to any preceding claim, wherein the air-inlet opening is defined by the side wall, the foil deflecting wall and the plate.

12. An inhaler apparatus according to claim 11 , wherein the air-inlet opening lies on a plane substantially perpendicular to the plate.

13. An inhaler apparatus according to any preceding claim, wherein a second side of the foildeflecting wall forms a second cutting edge.

14. An inhaler apparatus according to claim 13, wherein the second cutting edge runs from the piercing tip to the second end of the foil-deflecting wall at where the second end of the foil deflecting wall meets the plate.

15. An inhaler apparatus according to claim 13 or 14, wherein the second cutting edge is configured to cut a straight line in the seal of the blister.

16. An inhaler apparatus according to any of claims 13 to 15, wherein the cutting edge and the second cutting edge meet at the piercing tip, and form an acute angle therebetween.

17. An inhaler apparatus according to any preceding claim, in which the piercer is configured to cut a triangular flap in the seal of the blister, such that the triangular flap is deflected by the foil-deflecting wall.

18. An inhaler apparatus according to any preceding claim, wherein the air-inlet opening lies on a plane substantially perpendicular to the plate and at an angle of between about 45 to 135 degrees from a plane substantially perpendicular to the plate and extending between a centre of the air-outlet piercer and the piercing tip.

19. An inhaler apparatus according to any preceding claim, wherein the plurality of air-inlet piercers are positioned at the same radius from the axis of the air-outlet piercer.

20. An inhaler apparatus according to any preceding claim, wherein the plate comprises four air-inlet piercers.

21. An inhaler apparatus according to any preceding claim, wherein the air-inlet piercers are arranged symmetrically around the air-outlet piercer.

22. A drug delivery device for aerosolising a powdered medicament contained within a circular blister, the device comprising: a blister containing the medicament, and comprising a circular blister pocket sealed by a pierceable seal; and an inhaler apparatus according to any preceding claim.

23. A drug delivery device according to claim 22, in which the dimensions of the outlet and the inlets are selected so that the rate of airflow inhaled by a user through the inhaler is limited by airflow through the outlet.

24. A drug delivery device according to claim 22 or 23, in which the depth of the blister is greater than 1.2 times the distance which the air-outlet piercer extends into the blister, and is preferably 1.5 or 2 or 3 times the distance which the air-outlet piercer extends into the blister.

25. A drug-delivery device according to any of claims 22 to 24, in which the blister pocket has a parabolic cross section.

26. A drug-delivery device according to any of claim 22 to 25, in which all of the air inhaled by a user passes through the blister.

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