AEROSOL GENERATING DEVICE WITH AIR FLOW CONTROL

The invention relates to devices, technologies and methods for the administration of a substance by inhalation, especially for administering medicaments to the lungs of a patient by the aerosolization of pharmaceutical formulations using energy created by patient inhalation. The pharmaceutical formulations may be in the form of a powder formulation.

BACKGROUND OF THE INVENTION

In the disclosure of the present invention reference is mostly made to the treatment of diabe- tes by infusion of insulin, however, this is only an exemplary use of the present invention.

Effective drug delivery to a patient is a critical aspect of any successful drug therapy, and a variety of drug delivery techniques have been proposed. For example, one convenient method is the oral delivery of pills, capsules and the like. However, oral delivery can in some cases be undesirable in that many drugs are degraded in the digestive tract before they can be absorbed. Another technique is subcutaneous injection as traditionally used for the administration of insulin which for the time being cannot be administered orally. One disadvantage to this approach is low patient acceptance, for which reason it has been proposed to use pulmonary delivery also for insulin.

Of particular interest to the invention are pulmonary delivery techniques which rely on the inhalation of a pharmaceutical formulation by the patient so that the active drug within the dispersion can reach the distal (alveolar) regions of the lung. A variety of aerosolization systems have been proposed to disperse pharmaceutical formulations. For example, US 5,785,049 and US 5,740,794, the disclosures of which are herein incorporated by reference, describe exemplary powder dispersion devices which utilize a compressed gas to aerosolize a powder. Other types of aerosolization systems include so-called MDI's (which typically have a drug that is stored in a propellant), nebulizers (which aerosolize liquids using compressed gas, usually air), and the like.

Another technique which is of interest to the invention is the use of inspired gases to disperse the pharmaceutical formulation. In this way, the patient is able to provide the energy needed to aerosolize the formulation by the patient's own inhalation. This insures that aerosol generation and inhalation are properly synchronized just as it may be possible to provide a device which is simpler to manufacture and more economical in use. Utilization of the patient's inspired gases can be challenging in several respects.

The powder may be provided in bulk form from where a desired amount of powder can be metered and moved into flow communication with the airway through which the patient is inhaling air to the lungs, this allowing the powder to be de-agglomerated and aerosolized. The powder may also be provided in pre-metered doses, the doses typically being contained in sealed containers formed in a carrier, either as a single-dose carrier or a multi-dose carrier. For example, US 6,1 16,239 discloses inhalation devices using a rotationally arranged disc- formed carrier comprising a plurality of powder-filled cavities, whereby rotation of the disc brings a new dose to be inhaled into flow communication with the airway. US 5,873,360 and US 7,171 ,965, which are hereby incorporated by reference, disclose inhalation devices for use with a medicament pack in which a plurality of powder-filled containers (or blisters) is defined between two strip-formed sheets peelable secured to each other. The device comprises means for peeling the sheets apart to open the containers consecutively, and an airway with an outlet communicating with the opened container, through which a user can inhale me- dicament in powder form from the opened container. The user's inhalation may also be used to actuate the device, e.g. as shown in WO 01/85245 in which a MDI device is actuated by the patient's inhalation moving a triggering membrane a small distance.

A challenge in utilizing the patient's inspired gases is that the inspiration flow rate can drasti- cally vary between individuals just as the timing between different actions may vary if they are performed manually. Such variability may affect the ability of the formulation to be dispersed within a gas stream, the ability to de-agglomerate a powdered formulation, and/or the ability of the aerosolized formulation to adequately reach the deep lung. This problem is addressed in e.g. US 6,606,992 (which are hereby incorporated by reference) wherein an in- haler is disclosed comprising a burst valve allowing a flow of air through a powder formulation when a given flow or vacuum is created by the patients inhalation.

Having regard to the above, it is the object of the present invention to provide devices and methods for regulating and managing the flow of inspired gases that may be utilized when dispersing a pharmaceutical formulation and which assures one or more of the following: enhancing the ability of a formulation to be dispersed within a gas stream produced by patient inhalation, enhancing the ability to de-agglomerate a powdered formulation, enhancing the ability for the patient to use the device in a consistent and correct way, thereby contributing to enhance the ability of the aerosolized formulation to adequately reach the deep lungs of the patient. It is a further object to provide devices and methods which are user-friendly thereby promoting correct and consistent use of the device.

DISCLOSURE OF THE INVENTION

In the disclosure of the present invention, embodiments and aspects will be described which will address one or more of the above objects or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments.

Thus, in a first aspect, the present invention provides an aerosol generating device comprising (a) an airway cavity in flow communication with a first air inlet and an air outlet adapted to be connected to the airway of a patient, (b) a receptacle member comprising first valve con- trolling means, the receptacle member having a receptacle cavity containing an aerosolize- able drug formulation, and (c) a first valve controlling air flow between the first air inlet and the airway cavity. The receptacle member is moveable relative to the airway cavity between a first position in which there is no flow communication between the receptacle cavity and the airway cavity and a second position in which there is flow communication between the recep- tacle cavity and the airway cavity, wherein the device is operatable between a first state in which the receptacle member is in its first position and the first valve is closed and there is no flow communication between the first air inlet and the airway cavity, and a second state in which the receptacle member is in its second position and the first valve is open and there is established flow communication between the first air inlet and the receptacle cavity, thereby allowing a flow of air between the first air inlet and the air outlet extracting drug formulation from the receptacle cavity, and wherein the first valve is controlled by the first valve controlling means. By this arrangement the flow of air through the airway cavity can be controlled by the position of the receptacle member in a simple and reliable way. The receptacle member may be moved manually by the user or the device may be provided with user actuatable drive means for moving the receptacle member between its first and further position(s), e.g. a spring-driven mechanism. The means for moving the receptacle member may also actuated by the patient's inhalation effort.

The receptacle member may be moveable relative to airway cavity between the first position, an intermediate position and the second position, and wherein in the intermediate position the first valve is open but there is no flow communication between the receptacle cavity and the airway cavity. In this way it is provided that a flow of air has been created in the airway cavity before the drug formulation is brought into flow communication with the airway cavity.

The first valve may comprise a first valve opening having a closed and an open state controlled by the first valve controlling means. The opening may be provided with a valve mem-

ber actuated by the valve controlling means (e.g. a projection) arranged on the receptacle member, however, the receptacle member may comprise a first closure portion adapted to engage the first valve opening in the closed state thereof, and a first flow permitting portion adapted to engage the first valve opening in the open state thereof. The closure portion may be a planar portion of a blister member and the first flow permitting portion may be in the form of a first opening or cut-out portion formed in the receptacle member. In this way the receptacle member serves directly as a valve member.

In an exemplary embodiment the aerosol generating device is provided with a second valved inlet and thus further comprises a second air inlet, and a second valve controlling air flow between the second air inlet and the airway cavity, wherein the receptacle member comprises second valve controlling means. Such a device is operatable between the second state in which the second valve is closed and there is no flow communication between the second air inlet and the airway cavity, and a third state in which the second valve is open and there is established flow communication between the second air inlet and the airway cavity, thereby allowing a flow of air between the second air inlet and the air outlet, and wherein the second valve is controlled by the second valve controlling means. The second valve system could be used to control e.g. a flow of chaser air through the airway cavity.

The receptacle member is preferably moveable relative to airway cavity between the first, the second and a third position corresponding to the first, second and third state. The second inlet may be controlled by the receptacle member in the same way as the first inlet, i.e. the receptacle member may comprise a second closure portion adapted to engage a second valve opening in the closed state thereof, and a second flow permitting portion adapted to engage the second valve opening in the open state thereof.

In exemplary embodiments the receptacle cavity contains a powder drug, and the first air inlet is a tangential air inlet (i.e. comprising a tangential component), such that a flow of air introduced through the tangential air inlet creates a swirl of air in a portion of the airway cav- ity, and wherein, when the receptacle cavity is in flow communication with the airway cavity, the swirl of air in the airway cavity creates a flow of air in the receptacle cavity, whereby the combined flow of air in the airway cavity and in the receptacle cavity results in powder de- agglomeration and transport of the de-agglomerated powder towards the air outlet.

For the above-disclosed embodiments the device may comprise (a) a drug carrier comprising (i) a receptacle member having a receptacle cavity containing a powder drug, and valve con-

trolling means, and (ii) a lid peelably attached to the receptacle member thereby defining a container, the lid comprising a lower surface facing the receptacle member and an opposed upper surface, and (b) a peel structure engaging the upper surface of the peelable lid in sliding engagement therewith, wherein the aerosol generating device is adapted in such a way that pulling the peelable lid results in sliding movement between the peelable lid and the peel structure, thereby opening the container and bringing the receptacle cavity in flow communication with the airway cavity.

The receptacle member may comprises a plurality of receptacle cavities containing a powder drug, the cavities and the peelably lid thereby defining a plurality of containers, each cavity being associated with corresponding valve controlling means. Alternatively, the device comprises an elongate receptacle member having a plurality of receptacle cavities arranged along the length thereof and being peelably attached to the lid, thereby defining a plurality of containers, each cavity being associated with corresponding valve controlling means.

The drug carrier may comprises a plurality of individual receptacle members peelably attached to the lid along the length thereof, thereby defining a plurality of containers, each cavity being associated with corresponding valve controlling means. Alternatively, the receptacle member has an elongate configuration having a plurality of receptacle cavities arranged along the length thereof and being peelably attached to the lid, thereby defining a plurality of containers, each cavity being associated with corresponding valve controlling means.

Above an aerosol generating device comprising a receptacle member containing an aerosol- izeable drug formulation has been described, however, in a second aspect the present inven- tion also provides an aerosol generating device per se for use with a corresponding receptacle member containing an aerosolizeable drug formulation, e.g. the receptacle member or drug carrier may be removable from the device and replaced by a corresponding new receptacle member or drug carrier.

In a further aspect of the invention a method is provided, comprising the steps of (a) providing an aerosol generating device comprising an airway in flow communication with an air inlet and an air outlet adapted to be connected to the airway of a patient, a receptacle member comprising valve controlling means, the receptacle member having a receptacle cavity containing an aerosolizeable drug formulation, and a valve controlling air flow between the air inlet and the airway, (b) moving the receptacle member between a first position in which there is no flow communication between the receptacle cavity and the airway and a second

position in which there is flow communication between the receptacle cavity and the airway, and (c) in response to movement of the receptacle member opening the valve using the valve controlling means, thereby allowing a flow of air between the air inlet and the air outlet. The method may comprise further steps as described in connection with the above disclo- sure of embodiments of an aerosol generating device.

As used herein, the term "drug" is meant to encompass any drug-containing formulation capable of being aerosolized. Representative drugs include pharmaceuticals such as peptides, proteins, and hormones, biologically derived or active agents, hormonal and gene based agents, nutritional formulas and other substances.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following the invention will be further described with references to the drawings, wherein

fig. 1A shows a schematic cross-sectional representation of an aerosol generating device in a situation of use, fig. 1 B shows a schematic cross-sectional view an the inlet end of an airway cavity, fig. 2 shows a further embodiment of an aerosol generating device in an unassembled state, fig. 3 shows in a schematic cross-sectional representation an embodiment of an aerosol generating device in a situation of use, figs. 4A-4D show different states of use for an aerosol generating device of the type shown in fig. 2, a portion of the device being removed, fig. 5 shows a partial cross-section of a further aerosol generating device, fig. 6 shows a yet further aerosol generating device, fig. 7 shows an exploded view of the aerosol generating device of fig. 6, figs. 8A and 8B show cross-sectional views of the aerosol generating device of fig. 6 in different conditions of use, figs. 9A and 9B show further cross-sectional views of the aerosol generating device of fig. 6 in different conditions of use, figs. 10A, 10B and 10C show cross-sectional views of parts of the aerosol generating device of fig. 6 in different conditions of use, fig. 11 shows a multi dose peel mechanism, and figs. 11A and 1 1 B show a further multi dose peel mechanism.

In the figures like structures are mainly identified by like reference numerals.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

When in the following terms such as "upper" and "lower", "right" and "left", "horizontal" and "vertical" or similar relative expressions are used, these only refer to the appended figures and not to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only.

Firstly, with reference to figs. 1-4 aerosol generating devices (or "inhalers") will be described which may be used in combination with the breath actuation mechanism of the present invention. Aerosol generating devices incorporating the breath actuation principle of the present invention will be described with reference to figs. 5-10.

More specifically, in fig. 1A the housing 10 comprises a generally oblong and generally tubu- lar airway cavity 30 having a lower opening 31 along its length and comprising an air inlet 32 and an opposed (i.e. downstream) air outlet 35 adapted to be connected to the airway of a patient. The air inlet has a generally tangential orientation thereby creating a swirling air flow in the airway cavity as air is drawn through the cavity from the air inlet to the air outlet (see below). The housing further comprises a support surface 40 for supporting an upper surface of a free portion of a peelable lid in sliding engagement therewith (see below).

The inhaler is provided with a drug carrier 50 comprising a receptacle member 51 having a receptacle cavity 52 containing a powder drug, and a foil lid 55 peelably attached to the receptacle member thereby defining a sealed container 54, the lid comprising a lower surface facing the receptacle member and an opposed upper surface, wherein the lower surface corresponding to the receptacle cavity faces the powder drug in an initial sealed condition of the container. The two layers will typically be formed from aluminium-polymer laminates. In an initial condition (not shown) the sealed container is arranged outside the airway cavity opening 31 with a leading portion 53 of the receptacle member slidingly engaging and closing the airway cavity opening. A free portion 56 of the lid is slidingly guided around a peeling edge 41 and subsequently supported on the support surface 40. An end portion of the lid is connected to a peeling mechanism (not shown) for pulling the lid. The lid may also be pulled manually as in the embodiment shown in figs. 2-4. How the moving receptacle member can serve to control flow communication between the receptacle cavity and the airway cavity will be described in greater detail with reference to figs. 2-4 and figs. 5-9.

In the fig. 1A embodiment the angle between the tubular airway cavity and the drug carrier is approximately 20 degrees, however, it may vary between 0 and 180 degrees (i.e. the receptacle and the air flow may move against each other). Further, the receptacle may be moved transversely relative the airway cavity, e.g. when using a rotationally arranged disc-formed carrier comprising a plurality of powder-filled cavities.

When a flow of air has been generated between the air inlet and outlet, and thereby a swirling air flow in the airway cavity, the inhaler is actuated either manually or automatically (e.g. triggered by the users inhalation) and the lid is pulled in the direction indicated by arrow 81 , this resulting in the receptacle member moving in the direction indicated by arrow 82, and the container being peeled open, whereby the receptacle cavity is moved into flow communication with the airway cavity. As the receptacle cavity starts to come into flow communication with the airway cavity, the airway swirl will start to generate a secondary swirl in the receptacle cavity generally in the plane of the opening. From experiments conducted it has been found that this secondary swirl is created very early when only a small portion of the receptacle cavity is in direct flow communication with the airway cavity. This situation can be compared with a situation in which two gear wheels are in engagement with each other. Even when the receptacle cavity is in full flow communication with the airway cavity as seen in fig. 1A, it has been found that a secondary swirl is still present in the receptacle cavity. Indeed, in the border region between the receptacle cavity and the airway cavity a complex mixed flow will exist which will bring the powder into the airway cavity swirl and towards the air outlet. From experiments it appears that the majority of de-agglomeration takes place in the receptacle cavity.

As appears from fig. 1A the air inlet 32 is arranged to provide a flow of air past the exposed lower surface of the peelable lid and through the receptacle cavity, the flow of air thereby removing powder drug from the peelable lid and the receptacle cavity.

As shown in fig. 3 the air inlet and the airway cavity are configured in such a way that the flow of air creates a swirling air flow in a portion of the airway in flow communication with the receptacle cavity, whereby the rotating motion of air in the swirl extracts powder drug from the receptacle as air revolves between the airway cavity and the receptacle cavity.

To create the swirl one or more tangential air inlets 32 may be provided as shown in fig. 1 B. Although a swirling air flow is created in the airway cavity to provide de-agglomeration of the powder, it may be desirable that the aerosol flow leaving the inhaler has a predominantly ax-

ial flow to avoid uneven particle distribution in the inhaled air. This may be achieved by the provision of generally axially oriented vanes 36 arranged in the airway outlet as indicated in fig. 1A. Alternatively, counter-rotating additional air inlets that straighten the flow downstream of the swirl chamber may be provided.

In figs. 2 and 3 an alternative, fully manual and thus simple design for an inhaler 100 is shown. In this embodiment the carrier is represented by a blister member 120 (i.e. corresponding to receptacle member 51 of fig. 1A) comprising a lower base portion 125 in which the receptacle cavity 121 is formed, the receptacle being closed by a peelable lid foil 128. The inhaler can be designed such that it consists of only one foldable mechanical part and one aluminium/ aluminium blister. The mechanical part containing airway inlet and outlet, swirl chamber (i.e. corresponding to the airway cavity 30 of fig. 1 ), lid support, sliding groove and connection for a mouthpiece is depicted in fig. 3. More specifically, a lower part 115 serves as lid and includes an opening 132 for the airway inlet and a groove 1 16 for slidingly receive the receptacle. A top part 1 10 includes an oblong swirl chamber 130 with an opening

131 , a U-shaped channel portion 133 to be arranged in front of a wedge in an assembled state and serving as part of the tangential air inlet, and the air outlet 135 adapted for connection to a mouthpiece. In the shown embodiment the outlet is tangential relative to the airway chamber but alternatively it may be axial as in the fig. 1A embodiment. A wedge-formed lid support 1 18 used for peeling and supporting the blister lid foil is connected to the lower part. When assembling the inhaler, a blister member is placed on the lower part with the receptacle arranged in the groove, where after the wedge section is folded over. A freely extending portion 129 of the lid foil of the blister unit is then folded backwards over the wedge section. Final assembly is achieved by folding the top part hereby locking the folded assembly with a tab portion of the lid foil protruding from the inhaler. In the fig. 3 embodiment air enters from the top of the housing and not from the bottom as in the embodiment shown in figs. 2 and 4A-4D.

With reference to figs. 4A-4D use of a device of the type shown in fig. 2 will be described. In the figures a portion of the housing is cut away, this allowing a view to the air inlet opening

132, the airway cavity 130, the lid support 118 and the blister member 120 comprising the receptacle 121 and a surrounding planner portion 123 with a cut-out portion 124. The specific design of an air inlet 132 controlled by a cut-out portion in the blister member is only an example of how the flow of air and the movement of the blister member can be synchronized and is not part of the present invention.

In a situation of use the patient starts to inhale through the mouthpiece, either freely through the air inlet or against a closed valve as shown, thus feeling a resistance to inhalation, this as shown in fig. 4A showing the device in an initial situation. When inhaling or attempting to inhale the user starts to pull the tab 129 whereby the lid will be pulled around the front peel edge of the lid support 118, this resulting in the cut-out portion 124 being moved into register with the inlet opening 132 whereby air is sucked through the U-shaped channel and tangen- tially into the airway cavity where it creates a swirl 138 before leaving the device through the mouthpiece 136, see fig. 4B. Just after the swirl is established in the airway cavity the receptacle is moved into flow communication with the airway cavity, this allowing a flow of air in- traduced through the air inlet 132, 133 to create a swirl in the receptacle cavity as it is moved into flow communication, thereby de-agglomerating and extracting powder formulation from the receptacle, see fig. 4C. As appears, the air inlet 133 is designed so that air is directed over the peeled lower surface of the foil lid, this cleaning the lid foil for powder sticking thereto. As the powder is moved in the receptacle cavity and in the swirl chamber by the swirling air it is subjected to high shear forces whereby it is de-agglomerated before it exits through the air outlet and mouth piece 136. Thus, in respect of the receptacle and the airway cavity the same relative movement takes place as in the above described first embodiment. After the receptacle has been emptied the receptacle may be moved further forwards (not shown) this allowing a second cut-out portion in the blister member to be moved into register with the airway cavity, this resulting in a secondary flow of air via the groove 1 16 flushing the cavity.

As appears, by appropriate design of the air inlet it is possible to use the blister member as a sliding valve controlling the airflow through the swirl chamber. As shown, the blister may be provided with a circumferential portion 123 comprising a surface portion and an opening or cut-out portion, wherein the surface portion serves as a closed valve when the receptacle member is in its initial position, and the opening or cut-out portion serves as an open valve when the receptacle member is in an actuated position. As can be seen in fig. 4B a valve opening (here: a cut out portion 124) in the blister is designed to open the air inlet a little prior to the point in time when the receptacle is moved into communication with the airway cavity, this allowing a swirl to be formed in the airway cavity before the combined swirl chamber is created. Further embodiments of aerosolising devices of the type shown in fig. 1A is described in applicants co-pending application PCT/EP2008/051052 which is hereby incorporated by reference.

Fig. 5 shows an embodiment of an aerosol generating device 201 incorporating a breath actuation mechanism. More specifically, the device comprises a housing 210 in which a slidable spring-biased carrier 220 is arranged. The housing comprises a generally oblong airway cavity of the same general design as shown in figs. 2-4. A variable-volume chamber 240 is connected to the air outlet 235 via a conduit and the airway cavity and comprises a rigid cylindrical chamber 242 and a slidable piston 243 mounted therein, the cylinder and piston defining the variable-volume chamber. A bellows seal 244 is provided between the piston and the cylindrical chamber. The variable-volume chamber is associated with actuatable triggering means 245 responsive to evacuation of a volume of air from the chamber whereby actuation of the triggering means releases the carrier 220 which subsequently opens a valve (not shown) thereby allowing a flow of air through an air inlet to the air outlet. The slidable carrier 220 comprises a generally oblong receptacle (either formed in the carrier or by a blister member arranged in the carrier) containing the aerosolizeable powder drug formulation and has an upper opening closed by a peelable foil lid. A free portion of the foil lid is wrapped around a stationary wedge portion (as in fig. 3) and fixed thereto. In the initial position the upper surface of the carrier serves as closure means for the airway cavity opening, whereas the foil lid serves as the closure means for the receptacle. When the carrier is actuated and starts to move the foil is peeled from the receptacle as shown in fig. 3.

Fig. 7 shows in an exploded view an embodiment of an aerosol generating device 301 incorporating a further breath actuation mechanism. More specifically, the device comprises a main housing portion 310 with an air outlet 335, a lower portion 315, an upper blister holder portion 350, a piston 343, a sledge 360, a releasable lock 325, and a biasing spring 368. Fig. 6 shows the device 301 in an assembled state. In the device a blister member 370 with a peelable lid 378 is arranged, see fig. 8A.

As seen in fig. 8A, when the lower portion 315 and the upper blister holder portion 350 is attached to the main housing portion a generally closed square-cylindrical cavity is formed in which the square piston is slidably mounted, a variable-volume chamber 340 being formed between the upper surface of the piston and the cavity, a bellows seal 344 being provided between the periphery of the piston and the lower portion. The piston comprises a release member 345 projecting from its upper surface and being guided in an opening 352 in the blister holder portion. The main portion comprises an airway cavity 330 with a lower opening 331 which initially is in flow communication with the chamber 340.

The blister holder portion 350 comprises a generally planar lower portion 351 and an upper tubular portion 355 in which the sledge 360 is slidingly mounted. The lower portion comprises a left-most wedge edge 366 around which the peel foil 328 is mounted, and on the lower surface a gripping flange 353 is arranged which in combination with gripping flanges 311 , 312 on the main housing portion serves to hold the blister member yet allowing it to be moved in a controlled manner, see fig. 8A. Below the flange 353 an air inlet 354 in communication with the exterior is arranged.

The sledge 360 has a right-most tube portion with an upper slot 361 along its length, this al- lowing a spring support member 356 of the blister holder portion to project into the sledge tube portion, the springs 368 being mounted in an initially compressed state between the spring support member and a pin 362 attached to the right-most end of the sledge. The sledge further has a left-most main portion 365 comprising a releasable lock 325 which initially engages the opening 352 in the blister holding portion, as well as it serves to hold the proximal end 379 of the peelable foil lid 378 (see below).

The blister member 370 comprises a base sheet 375 in which an oblong receptacle cavity 371 with an opening 372 is formed, the remaining of the base sheet forming a generally planar circumferential portion comprising first and second cut-out portions 373, 374 (see fig. 9A). The peelable lid 378 comprises a distal portion attached to the circumferential portion thereby covering the receptacle cavity to form a sealed blister cavity containing an amount of an aerosolizeable drug powder formulation, as well as a proximal portion arranged around the wedge edge and attached to the main portion of the sledge.

In a situation of use the piston, the sledge and the blister member will be actuated and move and three series of "events" will take place related to these 3 movements.

Figs. 8A, 9A and 10A show the device in its initial condition. When the user starts to inhale through the mouthpiece 335 air is evacuated from the chamber 340 via the airway cavity 330 through the lower opening 331 which initially is in flow communication with the chamber 340. This results in the piston moving upwards whereby the release member 345 engages and releases the sledge lock 325, see fig. 8B, whereby the sledge starts to move towards the right.

Fig. 10A shows the blister holder 350 and the blister member 370 in the initial condition with the other components removed. The free proximal portion of the peelable lid 378 is wrapped

around the stationary wedge edge 366 with upstanding proximal end of the lid foil mounted in the main portion 365 of the sledge 360, see fig. 8A. As the sledge is moved to the right the foil is peeled off the base sheet, whereby the blister is opened and moved to the left (see figs. 10B and 10C) and thereby into flow communication with the airway cavity.

As the blister member is moved it also serves to open and close airway openings. In the initial position as seen in fig. 9A the airway cavity is in flow communication with the variable- volume chamber through cavity opening 331 , and the air inlet openings 332 and 354 are closed by the blister member. As the blister member is moved to the left the cavity opening is closed and the air inlet openings 332 and 354 are opened (by moving the first cut-out portion 373 into register with the inlet 332 and moving the blister member out of register with the inlet 354), this providing that air is drawn through the air inlet opening 354, the variable-volume chamber 340 and the air inlet opening 332 before it enters the airway cavity through a U- shaped channel-formed air inlet portion arranged in front of the wedge (this as best shown in fig. 4B) and here creates a swirl before it is inhaled by the patient. Just after the swirl is established in the airway cavity the receptacle is moved into flow communication, this allowing the airway swirl to generate a secondary swirl in the receptacle cavity, thereby extracting powder formulation from the receptacle. As the powder is moved in the receptacle cavity and the airway cavity by the swirling air it is subjected to high shear forces whereby it is de- agglomerated before it exits through the air outlet 335. After the receptacle has been emptied the receptacle is moved further to the left and out of flow communication with the airway cavity, however, the blister member continues to move this resulting in the first cut-out portion 373 being moved out of register with the air inlet 332 whereby the inlet is closed by the planar portion of the blister member, and the second cut-out portion 374 being moved into regis- ter with the airway cavity opening 331 , this resulting in a secondary flow of air flushing the airway cavity. Typically it is desirable that the combined flow resistance is lower for the secondary flow. As appears, it is important that a good seal is provided between the upper surface of the blister member and the lower surface of the blister holder. In the shown embodiment the air inlet opening for the flushing air flow is provided by the opening also used for the receptacle cavity, however the inlet opening for the flushing air flow could be provided as a separate inlet opening.

With reference to fig. 11 a multi dose peel mechanism 400 will be described, whereby peeling and conveying a blister tape can be carried out by a mechanism using a spring as the power source. The mechanism is designed to peel a blister tape of the type described in US 5,873,360 which is hereby incorporated by reference. The shown embodiment is a prototype

mounted on a board 401 and designed to test the peeling mechanism for which reason an airway is not provided.

The blister tape 410, comprising an elongate receptacle member 411 having a plurality of receptacle cavities 412 arranged along the length and a peelable lid foil layer 413, is kept coiled up in a first chamber 421 , led out of the chamber around a driving wheel 430 and into a second chamber 422. In the shown embodiment the cavities have a longitudinal configuration arranged transversely on the blister tape but they may have any desirable configuration. Further, two cavities could be arranged side-by-side, e.g. comprising two different powders. The lid foil is separated from the blister tape at a peeling pin 431 and wound up on a peeling wheel 432 to which it is attached. When a loading mechanism 435 is turned counter clock wise a spring wheel 436 is turned and a spring (not shown) mounted inside the spring wheel is loaded and held in an actuated condition until released. The spring wheel has ratchet arms that click inside the driving wheel when the loading arm is turned. The driving wheel is pre- vented from turning by a trigger that may be either manual or released by the user's inhalation. In a dial-a-dose embodiment the spring can be loaded 1 through 5 steps (clicks) corresponding to the desired number of doses. Hereby the driving wheel is allowed to turn which again turns the peeling wheel by means of gear wheels 437, 438. The motion continues until the spring wheel meets a spring wheel stop. A tape support member 439 keeps the cavities on the blister tape close to the driving wheel to ensure contact. The airway cavity and air flow channels are not shown but are to be positioned in the area where the cavities are opened. As appears, in this embodiment the oblong cavities are arranged transversely on the receptacle member. Corresponding to the above-described single-blister embodiments, the blister tape may also be provided with openings or cut-out portions controlling the flow of air.

With reference to figs. 11A and 1 1 B a further multi dose peel mechanism 500 will be described, whereby peeling and conveying a blister tape can be carried out by a mechanism using a spring as the power source. The shown embodiment is a prototype designed to test the peeling mechanism.

In this embodiment the blister tape 510 comprises a plurality of individual receptacle members 51 1 each having a receptacle cavity 512 and being peelably attached to a strip-formed lid foil member 513 along the length thereof, thereby defining a plurality of containers. The mechanism comprises a blister tape storage 521 , a peeling station 530 with a peeling edge (i.e. corresponding to the above-described embodiments), a spring-loaded peeling mechanism 540 with a peeling wheel 541 for taking up the lid foil 513, a priming wheel 542 and an

airway 550 with a vacuum-actuated trigger membrane for actuating the triggering mechanism

(arranged inside the peeling wheel) for the peeling mechanism. An advantage of using an inhalation controlled triggering mechanism is that the receptacle is opened during inhalation only, this minimizing the risk of an opened blister being left in the device. As appears, in con- trast to the fig. 11 embodiment only the lid foil is collected on the peel wheel whereas the individual receptacle member is discarded from the inhaler when it has been fully peeled off the lid foil. Alternatively, the receptacle member may be a continuous band as above, however, this would imply cutting off the used receptacle portion. In a situation of use the peel mechanism is activated by turning the priming wheel thereby loading the peel mechanism. When the trigger mechanism is released the peel wheel is allowed to turn a given angle corresponding to the peeling and forwarding of an individual receptacle member. When integrated into an inhaler, the receptacle member will be moved past an airway cavity as shown schematically in fig. 1A, a flow of air cleaning the lower surface of the lid foil and emptying the receptacle cavity for powder before the empty receptacle member is discarded.

The blister tapes shown in figs. 11 and 1 1A may be provided with valve means in the form openings and/or cut-out portions formed in the receptacle member(s) as described above with reference to figs. 4-9, e.g. corresponding to cut-out portions 124, 373. The lid foil may be formed without corresponding openings. Correspondingly, the lid foil may be provided with "camera" perforations allowing the lid foil to be pulled by a peeling mechanism, the blister part of the tape comprising no such perforations.

In the above-described embodiments the airway cavity has a generally oblong or tubular configuration in which the generated swirl has an axis along the length of the cavity and cham- ber. However, the airway cavity could also have other configurations, for example a disc- formed configuration.

In the above description of the preferred embodiments, the different structures and means providing the described functionality for the different components have been described to a degree to which the concept of the present invention will be apparent to the skilled reader. The detailed construction and specification for the different components are considered the object of a normal design procedure performed by the skilled person along the lines set out in the present specification.