Medicament dispenser

Technical Field The present invention relates to a sheet drive assembly component for use in a drug dispenser for drug dosing, in which the drug in powder or tablet form is transferred through a longitudinal blister strip consisting of a backing sheet having cavities formed and a top sheet applied thereto.

Background of the invention [0002] The use of inhalation devices for administering drugs, for example, in bronchodilatory treatment is well known. Such devices usually have a body or housing in which the drug carrier is located. The known inhalation device has a drug carrier in the form of an elongated blister strip containing a number of discrete doses of the drug in the form of a powder or tablets. The elongated blister strip has a backing sheet having sockets formed therein and a top sheet applied thereto, wherein the backing sheet and the top sheet can be separated by peeling to allow access to the contents of each nest. Such devices typically include a mechanism to provide access to these doses, including peeling means for peeling the cover sheet from the backing sheet. In this way, the medicine becomes available for administration to the patient.

[0003] Suitable tearing means are arranged to tear the backing sheet and the top sheet away from the opening station of the device. The tearing means usually have a sheet drive assembly (ground or top) for pulling the top sheet away from the seat base sheet that has been obtained at the opening station. In one embodiment, the driving means of the sheet are a constant diameter wheel on which the sheet is wound (e.g., top), the wheel having a useful winding surface whose diameter increases as more and more sheet (e.g., top) is wound around the replaced wheel.

[0004] The problem that we encounter when using such a fixed diameter wheel as the sheet drive assembly for propelling the drug carrier sheet is that the sheet winds around a circle whose useful winding diameter increases and thus its effective side pull (i.e. pull length) also increases. This is problematic because it is desirable to achieve a measurable pull action on the drug carrier socket at the opening station after startup to ensure that each drug carrier socket will undergo generally uniform indexing / opening action. Generally speaking, insufficient pulling action will result in unsuccessful opening of the seat, while excessive pulling will put pressure on the mechanical components and increase the force necessary to actuate the dispenser.

[0005] A solution to the above problem has been proposed in the PCT patent application No. WO 03/035509, in which compensating means are used to compensate for any increase in diameter of the useful winding surface of the wheel during use of the dispenser, thereby ensuring that said drug carrier will be evenly indexed at each activation of said dispensing mechanism.

[0006] Another known solution is FR-A-2659558.

[0007] The applicant has now discovered that a sheet drive unit (top or bottom) having the form of a hub housing a compensating means in the form of a central, mounted on a shaft torsion spring, provides particularly effective compensation for this increase in diameter.

[0008] Document WO-A-2004/067069 discloses a sheet drive assembly according to the preamble of claim 1 contained herein.

Summary of the Invention [0009] According to one aspect of the present invention, a drive assembly according to claim 1 is provided.

[0010] The present invention provides a sheet drive assembly for use in a drug dispenser comprising a drug carrier having a plurality of seats for a drug room in which said seats are arranged in length and are defined between the first and second sheets that are attached to each other and can be separated due to driven pulling action.

[0011] The sheet drive assembly has a base, usually circular (e.g., disk-shaped).

[0012] A shaft extends (e.g., rises) from the base. The shaft may be integrally formed with the base or it may be a separate part attached to the base. The shaft defines the axis of rotation around which the hub can rotate.

[0013] On the base there is a driving surface for receiving a drive for rotating the base about the axis of rotation. The base has a circular shape, respectively, and the drive surface extends circumferentially around this base.

[0014] Preferably, the drive surface is a toothed surface (i.e., it specifies a toothed surface), although other types of drive surfaces may be considered, including surfaces associated with friction or belt drive.

[0015] In one embodiment, the driving surface is integral with the base. The base defines the wreath accordingly, and the driving surface is located on the wreath. [0016] In another embodiment, the driving surface is on a separate part that connects to the base.

[0017] In a particular embodiment, the driving surface is on a ring that is mounted on the periphery of the base that receives it (for example, engages with it). The driving surface is located on the ring surface.

[0018] In one embodiment, the inner peripheral surface of the ring also has a toothed surface and the base has a ratchet arm, so the base and the ring engage on the principle of a ratchet mechanism. This latch engagement ensures that the ring can only rotate relative to the ground in one direction of rotation (for example, clockwise or counterclockwise), while rotation in the other direction of rotation prevents mutual rotation ratchet interaction between the inner, toothed surface of the ring and the ratchet base arm.

[0019] There is a torsion spring around said shaft. In the present context, the term "spring" means any spring-like spring element that can be stressed. The torsion spring defines the first and second spring arms, which arms usually extend (e.g., protrude) from the ends of the spring (e.g., upper and lower).

[0020] Suitably, the spring is a spiral spring. In one embodiment, the spring arms protrude away from the spring in a direction perpendicular to the axis of rotation defined by the spring turns. In another embodiment, the spring arms protrude away from the spring in a direction parallel to the axis of rotation defined by the turns of the spring.

[0021] Around the shaft and the torsion spring, a hub is mounted that can be rotated about an axis of rotation, defining the hub surface for receiving a base or top sheet, preferably a top sheet of said medicament carrier. The hub is usually fitted on a torsion spring and a shaft. The hub itself has a constant diameter, although its useful diameter for winding (i.e. the wheel plus the thickness of the top or backing sheet wound around it) will change in use when the sheet is arranged in this way. The hub is usually a massive construction and essentially incompressible in nature, at least around its diameter.

[0022] In other embodiments, the hub is mounted around the shaft so that it can rotate either clockwise or counterclockwise relative to the base, and thus such that the torsion spring it can also be tensioned in one direction or the other. [0023] The hub suitably has means for engaging the end of the sheet.

[0024] In one embodiment, the coupling means are markings or surface coatings applied to the hub to reinforce the friction contact between the hub and the sheet. [0025] In another embodiment, loop coupling means (e.g., a pin, hook, cutout or slot) are formed in the hub to engage the loop end of the sheet.

[0026] The torsion spring of the present sheet drive assembly operates to compensate for any increase in diameter of the useful diameter of the hub winding surface with a constant diameter when winding the sheet around it. It is therefore essential that the sheet drive assembly allows the torsion spring to be tensioned. Thus, the first base arm driver adopts the first torsion spring arm and the second hub arm driver adopts the second torsion spring arm, so the relative rotation of the base and hub causes the torsion spring to be tensioned.

[0027] In a preferred embodiment, the hub and base have a lock for locking the hub rotation relative to the base. Accordingly, the lock is at a certain angular distance from the initial position in which the torsion spring is not tensioned, to the position or any locking position (i.e. when the lock is engaged), thereby determining the known tension of the torsion spring.

[0028] In one embodiment, the change in "locking position" is obtained by changing the angle of the arm defined by the arm (s) of the torsion spring [0029] To induce known tension on the torsion spring, the hub therefore rotates (or in the direction of the direction of the direction of movement of the hands) clockwise or counterclockwise) from the initial position to the specific locking position in which the lock engages.

[0030] In one embodiment, the hub has a locking pin extending into one or more of the locking pin's seats in the base. In another embodiment, the base has a locking pin extending into one or more hub locking pins.

[0031] According to another aspect of the present invention, there is provided a drug dispenser for use with a drug carrier having a plurality of slots for a drug room in which said slots are arranged in length and defined between sheets, first and second, attached to each other and detachable as a result of driven pulling action, wherein said dispenser has an internal dispensing mechanism for accessing said medicament housed in said medicament carrier, said mechanism having:

a) an opening station for receiving the socket of said medicament carrier;

b) tearing means arranged to engage with the backing sheet and the nest top sheet that has been received at said opening station to detach such backing sheet and the top sheet from each other to open such nest, said tearing means having an assembly a driving sheet, as described above, for peeling away the top sheet and the base sheet of the socket which has been adopted at said opening station;

c) an outlet positioned to have a connection to an open socket through which the user can remove the drug from such an open socket; and

d) an indexer for indexing in connection with said drug carrier outlet outlet used in said drug dispenser, said in4 decoder being interconnected with said sheet drive assembly such that the movement of one is correlated with the movement of the other.

[0032] The medicament dispenser may be intended for use with a plurality of said medicament carriers, the internal dispensing mechanism being intended to provide access to said medicament housed in each of said plurality of medicament carriers, the opening station is intended to receive the receptacle of each of said plurality of drug carriers, and the indexer is used for indexing in connection with said outlet, sockets of each of said multiple drug carriers intended for use in connection with said drug dispenser.

[0033] The sheet drive assembly has a fixed diameter hub on which said base or top sheet, preferably a top sheet is wound, and said hub has a useful winding surface whose diameter increases as more and more sheet is wound around this hub.

[0034] The torsion spring acts to compensate for any increase in diameter of the usable diameter of the fixed diameter hub winding surface during use of the dispenser, and thus ensures that said drug carrier will be indexed evenly each time said dispensing mechanism is activated. The torsion spring also works to ensure that there is a minimum tearing force between the base sheet and the top sheet when the dispensing mechanism is actuated.

[0035] In particular, the torsion spring operates to change the characteristics of the hub drive function so as to compensate for any increase in diameter of the effective hub winding surface during use of the dispenser. Due to this, the drug carrier is evenly indexed (i.e., usually indexed by the same length of the strip) as a result of each activation of the dispensing mechanism, and the opening operation of the socket to which the strip is subject is also uniform.

[0036] The medicament dispenser described herein is suitable for use in conjunction with a medicament carrier having a plurality of seats for receiving a medicament, wherein said seats are substantially evenly spaced in length and defined between two sheets attached to each other, separated by peeling. The drug carrier is usually in the form of an elongated peelable blister strip.

[0037] It will be appreciated that the torsion spring operates to compensate for the increase in diameter of the useful winding surface of the wheel during use of the dispenser. It will be appreciated that the initial usable winding surface and associated initial hub drive "speed" is mainly a function of the (constant) initial hub diameter. Variations in which the initial useful winding surface is selected to determine specifically selected initial hub drive parameters are considered in this application.

[0038] In one variation, sometimes called the "unidirectional winding" mode, the initial usable winding surface is selected to initially provide ideal (i.e. uniform) indexing of the drug carrier. As the top sheet winds around the hub, the useful winding surface increases and the torsion spring acts to compensate for this increase.

[0039] In another variation, sometimes referred to as the "dual winding" mode, the initial usable winding surface is selected so as to initially provide non-ideal (i.e. uneven) indexing of the drug carrier because the hub diameter is not large enough. When the top sheet winds around the hub, the useful winding surface of the hub increases to the ideal diameter, and then, during further winding, continues to increase to the non-ideal (i.e. too large diameter). It should be realized that in this form the degree and nature of compensation provided by the torsion spring will change along with the winding function. The torsion spring initially works to compensate for the insufficient wheel diameter. This compensation decreases to zero at the point where the diameter of the useful winding surface is ideal. Then the compensation works gradually to compensate for too large a useful winding surface. The advantage of this approach is the overall reduction of the (average) compensatory torsional force acting on the drug carrier from a fixed zero (i.e. ideal) and allows the use of weaker tensioning means (e.g., a smaller torsion spring). In a preferred embodiment of this variety, the ideal useful diameter of the winding surface is selected so that it approximately corresponds to the point where half of the top sheet is wound onto the hub, in which case average (i.e. medium) the compensation effect on the support is close to zero throughout the entire life cycle.

[0040] Accordingly, said indexing mechanism is a rotatable indexing wheel having recesses, said indexing wheel being able to cooperate with a drug carrier in use with said drug dispenser, such that each of said recesses receives a respective seat of the drug carrier carrier sheet in use with said dispenser the drug.

[0041] Alternatively, said indexing means may be an indexing pawl that can move between a locking position in which said latch engages a seat on said drug carrier and prevents further peeling of the top sheet from it, and a release position allowing free movement of said drug carrier, and actuation of said drug dispenser activates said sheet drive and releases said indexing pawl from said drug carrier to allow peeling.

[0042] Accordingly, the drug dispenser further has an indexing lever for actuating said dispenser, said indexing lever being interconnected with said indexer and / or said sheet drive.

[0043] In one aspect, the sheet drive and / or indexer are actuated by an electronic drive system. The electronic drive system can also be used in conjunction with a mechanical drive system.

[0044] The electronic drive usually includes a motor, preferably an electric motor. The motor can provide a linear or rotary drive, but generally rotating motors are the most suitable. The motor may be, for example, a DC electric motor, piezoelectric motor (PZ), ultrasonic motor, solenoid motor or linear motor. Preferably, the electronic drive system includes a DC motor, PZ motor or ultrasonic motor.

[0045] Accordingly, the tearing means additionally have a guide for guiding the top sheet and the backing sheet in separate ways at the opening station. The top sheet passes around the guide part to drive the sheet.

[0046] Accordingly, the guide has a roller mechanism. The top sheet is guided over rollers to drive the sheet.

[0047] Accordingly, the internal mechanism additionally has a first chamber in which the strip initially fits and from which it is dispensed, and a second chamber for receiving the used part of the base sheet after it has been indexed and separated from the cover sheet.

[0048] Accordingly, the wall separates the first chamber and the second chamber. In one embodiment, the wall is movable to match the size of said first and second chambers. In another aspect, the wall is flexibly movable to match the size of the first and second chambers. In a further embodiment, the second chamber may expand to create space for the growing roll of the worn portion of the backing sheet.

[0049] Accordingly, the internal mechanism further has a third chamber for receiving a worn portion of the top sheet and a fourth chamber that houses the indexing mechanism. The fourth chamber may have a connection through a gap, which in turn extends upward inside the mouthpiece or outlet duct and has a connection to the air inlets.

[0050] Accordingly, the internal mechanism additionally has a crush wheel for crushing the drug seats after removal of the drug from them. The crushing wheel thus reduces the space occupied by the used part of the backing sheet.

[0051] Usually, an internal mechanism providing access to said drug that fits within said drug carrier is placed in the cassette.

[0052] In one embodiment, the invention provides a medicament dispenser for dispensing medicament having: a body, a handle shaped to fit within the body and movable with respect to said body, and said cassette containing said medicament carrier.

[0053] Accordingly, the movement of the handle relative to the body causes the cassette to move between the first position and the second position so that the cassette can be reversibly removed from the handle when the cassette is in the second position.

[0054] Accordingly, the first position is the dispensing position. Preferably, the second position is a dispensing position. The cassette can therefore only be removed from the holder when it is in the dispensing position.

[0055] Accordingly, the handle and body have attachment means for attaching the handle to the body. Preferably, said attachment means is a latch mechanism. [0056] Accordingly, said latch mechanism is a pin and hole arrangement. [0057] Accordingly, the handle may deflect relative to the body. Alternatively, the handle can rotate relative to the body.

[0058] Accordingly, the handle further has a stop to limit movement of the handle relative to the body. The bumper rests on the edge of the body at two points when it rotates. The handle can be designed to snap into place at these points. Thus, when the bumper rests against one edge of the body, it latches into the dispensing position, and when the bumper rests against the other edge of the body, it latches into the dispensed position.

[0059] Accordingly, the handle can slide relative to the body.

[0060] Accordingly, the handle additionally has a latch for holding the cassette. The latch may take the form of a spring pin that enters the opening or an integral latch that deforms under pressure, allowing the cassette to be removed.

[0061] Accordingly, the latch is childproof. The child lock can be implemented as a system that forces the user to perform two operations at the same time to remove the cassette. Other latch features may include shock or impact resistance, latch lockability, and orientation functions to ensure that the cassette can only be inserted in one way. The latch should also be easy to manufacture and install, should be strong, consist of a minimum number of components and penetrate minimal into the space in which the cassette is inserted.

[0062] Suitably, the handle has means for guiding the cassette into the handle. Preferably, said guide means is guide rails. Alternatively, the guide means are grooves, indentations or other shaped surface elements to define the "lock and key" relationship between the handle and the cassette. You can also use colored guides, arrows and any other surface markings.

[0063] Accordingly, the cassette additionally has an indexing lever. The indexing lever has a finger tip located outside the cassette body. The rest of the indexing lever is located inside the cartridge. The indexing lever may have teeth on its rear portion and / or teeth along the central portion.

[0064] Accordingly, the cassette has an additional mouthpiece.

[0065] In one embodiment, said mouthpiece is extendable. The mouthpiece slides out of the cartridge when the cartridge and handle moves from the dispensing position to the dispensing position.

[0066] Alternatively, the mouthpiece is retractable. The mouthpiece retracts when the cartridge and handle move from the dispensing position to the dispensing position. The drug dispenser may also be intended for nasal inhalation of the powdered drug and thus may have a nasal portion as an alternative to the mouthpiece. If the drug is in solid form, the dispenser may have an exit channel to release the tablet.

[0067] Accordingly, the body covers the mouthpiece and indexing lever when the cassette is in the dispensing position. This eliminates the need for a separate lid and protects the mouthpiece from dirt and contaminants during storage.

[0068] Accordingly, the cassette has an additional turned portion to abut against the handle. The folded-out part is located at the opposite end of the cassette in relation to the mouthpiece / nasal part / outlet and indexing lever and prevents the cassette from being inserted incorrectly into the holder because it is too wide to fit into the holder. The rolled out part is shaped to fit into the cut out part of the handle. Preferably, said turned up part has a section that is so turned up that it forms a gripping part.

[0069] Suitably, at least a portion of the handle and body are shaped to facilitate gripping by a user. Accordingly, the device can be operated with one hand.

[0070] Accordingly, the body additionally has at least one brush or wiper positioned along its upper or lower side that rubs against the upper and lower surfaces of the interior of the cassette. A brush or wiper operates to close the chamber into the drug room to cut off the drug carrier from the rest of the cassette body and prevent loose powder from entering the rest of the cassette. Loose powder may enter the chamber from the used part of the blister strip if the patient moves the strip by pressing the lever when he is not about to withdraw the dose or if he is unable to draw in all the powder.

[0071] Accordingly, the drug dispenser has an actuation or dose counter for counting the number of actuations of the indexing lever or dose releases from the cartridge. The dose counter can count the number of doses remaining or the number of doses taken. Accordingly, said dose counter is electronic. Alternatively, said dose counter is mechanical.

[0072] Alternatively, the blister strip has printed numbers corresponding to the doses in the sockets. Preferably, said printed numbers are visible through a window in the cassette. The device can be assembled as follows. The handle is snapped into the body. The cassette is mounted separately. The cassette body is preferably made in the form of two sections with all necessary axes or integral components formed in the base. Individual components such as indexing wheels, top-winding mechanisms, guide parts, etc. are then mounted in the base. Finally, the blister strip containing the drug (or other suitable drug carrier) can be inserted into the cassette. It can be wound inside the machine before attaching the top and sealing the cassette. Alternatively, the cassette can be made as a whole except for the opening left in its side to insert the blister strip or drug carrier. You can then close the hole tightly to complete the cassette assembly. The advantage of the second method of introducing the drug carrier into the device is its greater simplicity.

[0073] Accordingly, the drug dispenser additionally has an electronic data management system. The electronic data management system has an input / output function and has a memory for storing data; a microprocessor to perform operations on said data; and a transmitter for transmitting the signal associated with the data or the result of the operation on the data.

[0074] Accordingly, the drug dispenser additionally has a data entry system for entering user data into the electronic data management system. Preferably, the data entry system is a human machine interface (MMI), preferably selected from a keyboard, voice recognition interface, graphical user interface (GUI) or biometric interface.

[0075] Accordingly, the system additionally has a visual display module for displaying data from the electronic data management system. The display may have, for example, a screen such as an LED or LCD screen. More preferably, the visual display module can be connected to the drug dispenser body.

[0076] Accordingly, the drug dispenser additionally has a data link to connect to the local data memory to allow data transfer between the local data memory and the electronic data management system. The data memory can also have the function of data management, data analysis and communication.

[0077] The drug dispenser may additionally have a safety mechanism to prevent the unintentional repeated activation of the dispensing mechanism. In this way, the patient is protected against inadvertent intake of multiple doses of the drug when he is making a series of short, quick breaths. More preferably, the safety mechanism imposes a time delay between successive actuations of the release means. The time delay is usually between three and thirty seconds.

[0078] Accordingly, the drug dispenser further includes a release sensor for detecting the release of the drug from the cassette, said release sensor transmitting the release data to the electronic data management system.

[0079] Accordingly, the drug dispenser further includes a shock sensor for detecting the shaking of the drug container (e.g., before actuating the dispensing mechanism), said shock sensor transmitting data to the electronic data management system.

[0080] Suitably, any actuation sensor, release sensor or shock sensor is a sensor for detecting any suitable parameter, such as motion. Any suitable sensors are considered, including the use of optical sensors. The release sensor can detect any parameter that is affected by drug release, such as pressure, temperature, sound, moisture, carbon dioxide concentration and oxygen concentration.

[0081] The medicament dispenser, described herein, suitably comprises a medicament carrier having a plurality of seats for receiving a medicament in which said seats are arranged substantially uniformly in length and defined between two detachable tear-off sheets attached to each other. The drug carrier is usually in the form of an elongated, peelable blister strip.

[0082] Suitably, the peelable blister strip consists of a backing sheet in which blisters have been formed to designate seats for receiving separate doses of the drug, and a top sheet which is hermetically connected to the backing sheet, except for the area of ​​the blisters in such a way that the top sheet and backing sheet can be torn off. The sheets, the backing and the top, are usually welded together along their entire width except for the front end parts, where they are usually not connected at all. Thus, there are separate end portions of the backing sheet and top sheet at the end of the strip. The respective sheets, base and top, can be separated by peeling to free (for example, separately) the contents of each nest.

[0083] In one embodiment, the front end of either the base or top sheet is looped to allow better reception of the drive assembly by the hub.

[0084] In one embodiment, the drug carrier has a peelable blister strip in the form of a laminate. Accordingly, the laminate is a material selected from the group consisting of metal foil, organic polymeric material and paper. Suitable metal foils include aluminum foils or tinfoil having a thickness of 5 to 100 gm, preferably 10 to 50 Lim, such as 20 to 30 Lim, for example. Suitable organic polymeric materials include polyethylene, polypropylene, polyvinyl chloride and polyethylene terephthalate.

[0085] Suitably, the top sheet has at least the following successive layers: (a) paper, bonded to (b) polyester; bonded to (c) aluminum foil; which is covered with a heat-sealable varnish to be connected to the base sheet. The thickness of each layer can be selected according to the desired properties, but it is usually on the order of 5 to 200 microns, especially 10 to 50 microns.

[0086] Accordingly, the backing sheet has at least the following three successive layers: (a) oriented polyamide (OPA); bonded to (b) aluminum foil; bonded to (c) a third layer comprising polymeric material (e.g., polyvinyl chloride).

[0087] Various known techniques can be used to connect the top and back sheets, and thus to seal the blisters of the peelable strip. Such methods include gluing, hot bonding, heat welding, dielectric welding, laser welding, ultrasonic welding and hot tool welding. In particular, the top sheet and backing sheet of the peelable blister strip can be sealed in cold-bonding methods that are conducted at lower temperatures than conventional hot-bonding methods. Such "cold bonding" methods are particularly useful where the drug or drug composition intended for the blister room is heat sensitive (for example, degraded or denatured upon heating). Suitable "cold" sealing methods are carried out at a temperature in the range of 150-250 ° C, and more preferably 210-240 ° C.

[0088] The medicament may be a capsule, granule or tablet. Alternatively, the drug may be in the form of a powder. Preferably, when present in the form of a powder, the medicament comprises a pharmaceutical agent. Preferably, the pharmaceutical agent is selected from the group consisting of albuterol, salmeterol, fluticasone propionate and beclomethasone dipropionate and salts or solvates thereof and any combination thereof. Preferably, said combination comprises salmeterol xinafoate and fluticasone propionate.

[0089] Accordingly, the powdered drug additionally contains an excipient. Accordingly, said excipient is sugar.

[0090] In another aspect, the invention provides the use of a drug dispenser as described above.

Brief description of the drawings [0091] The invention will now be described with reference to the accompanying drawings, in which:

Fig. 1 is a perspective view of a drug carrier intended for a drug dispenser according to the present invention;

Figures 2a to 2k are perspective views of details of a sheet drive assembly according to the present invention;

Figures 3a to 3f are perspective views of an example of a sheet drive unit assembled as in Figs. 2a to 2k in a drug dispenser according to the present description;

Fig. 4a is a perspective view of the drug dispenser with the first drug carrier in the form of an elongated stripe inserted therein, and the insertion of a second drug carrier in the form of an elongated stripe;

Fig. 4b shows the drug dispenser of Fig. 4b with a second drug carrier disposed therein in the form of an elongated strip;

Figures 5a to 5h are perspective views of details of a second sheet drive assembly according to the present description;

Figures 6a to 6d are perspective views of the attachment of the drug carrier end to the second sheet drive assembly of Figures 5a to 5h.

Detailed Description of the Drawings [0092] Referring now to the drawing figures, Fig. 1 shows a drug carrier 100 for use in combination with a drug dispenser according to the present invention. The drug carrier is a flexible strip 102 defining a plurality of slots 104, 106, 108, each containing a dose of the drug in the form of a powder that can be inhaled.

[0093] The strip includes a backing sheet 110 in which blisters are formed to define the seats 104, 106, 108, and a top sheet 112 that is hermetically sealed to the backing sheet, except for the blister area, in such a way that the top sheet 112 and the backing sheet 110 can be torn off. The sheets 110, 112 are sealed together over their entire width, with the exception of the front end parts 114, 116, where they are preferably not sealed together at all. The front end portion 116 of the cover sheet 112 has a loop to engage the hub of the sheet drive assembly, as will be described in more detail below. Each of the sheets, i.e. the top sheet 112 and the backing sheet 112, is preferably made of a plastic-aluminum laminate, and they are preferably welded together.

[0094] The strip 102 is shown as having evenly spaced elongated slots 104, 106 and 108 extending transversely to the length of the strip 102. This is convenient because it allows the creation of a large number of slots 104, 106, 108 on the strip 102 of a given length. The strip 102 may have, for example, sixty or one hundred slots, but it should be understood that the strip 102 may have any suitable number of slots.

[0095] Figures 2a to 2k show assembly details of the sheet drive assembly in the present invention. In all figures, only the most important parts for a given figure have been marked.

[0096] Referring first to Figs. 2a and 2b, it can be seen that the circular base 220 has a toothed driving surface 225 located on the peripheral rim 222 and an integral, upwardly extending shaft 230. A torsion spring 240 having arms, lower 242 and upper 244 slides over the shaft 230 so that the lower spring arm 242 engages with the retaining groove 224 of the base 220. The shaft 230 also has a protruding rim 234, the function of which will become more apparent from the following description.

[0097] Referring now to Figs. 2c to 2e, the hub 250 slides over the shaft 230 so that it overlaps the torsion spring 240. It can be seen that the upper arm 244 of the torsion spring 240 is received by the locating groove 252 made in the inner part hubs 250. The upper end 232 of the shaft 230 projects through the central hole 254 of the lid end 256 of the hub 250. It is also seen that the hub 250 is provided with an upwardly projecting hook 258 adapted to receive the loop end of the sheet, as will be described in more detail below.

[0098] Referring now to Figs. 2f to 2h, the hub 250 is now rotated clockwise (in alternative embodiments, counterclockwise rotation is considered) by a specific rotation angle (in this case about 135 °) to base 220. It should be realized that because the arms of the torsion spring (not visible in Fig. 2f to 2h) connect to base 220 and hub 250, respectively, this rotation causes the torsion spring to be tensioned. The range of the specified angle of rotation is selected so as to align the stepped wall 255 of the bottom of the hub 250 with the edge of the wall 223 that forms part of the retaining groove 224 for the lower spring arm 242.

[0099] As shown in Figs. 2i to 2k, the hub 250 is then pressed all the way (i.e. down towards the base 220) so that its central hole 254 snaps on the periphery 234 of the shaft 230 to fix the hub 250 on the base 220. Torsion spring (not visible in Fig. 2i to 2k) does not unwind from its tensioned state as a result of the interaction between the stepped wall 255 of the bottom of the hub 250 and the edge of the wall 223 that forms part of the retaining groove 224 for the lower spring arm 242 (all these elements can only be seen in Fig. 2i).

[0100] The sheet drive assembly is now ready for use in a suitable drug dispenser.

[0101] Figs. 3a to 3f are perspective views of a power unit assembly

260 the drug dispenser described herein. The drive unit 260 is prepared for use in a drug dispenser intended for use with multiple drug carriers, each of the type shown in Fig. 1, and having a plurality of seats 104, 106, 108 for receiving a medicament, said seats 104, 106, 108 being spaced apart along the length of the strip and defined between the backing sheet 110 and the top sheet 112, except that sheets 110, 112 are attached to each other, and can be separated by tearing as a result of the driven pulling action.

[0102] Referring to Fig. 3a, the drive unit 260 is adapted to receive the sheet drive units, first 218a and second 218b, so that their hubs 250a, 250b protrude through holes 262a, 262b formed in the base 261 of the drive unit. The bases 220a, 220b of the drive assemblies 218a, 218b protrude upward from the holes 262a, 262b so that the respective hubs 250a, 250b are rotatably driven by the rotational drive motion of the toothed drive surfaces 225a, 225b of the respective bases 220a, 220b.

[0103] With reference to Fig. 3b, it can be seen that the toothed drive surfaces 225a, 225b of the respective bases 220a, 220b cooperate with a complex gearing 265 mounted on the base 261 of the drive unit 260. The gearing 265, and thus the rotation of each respective base 220a, 220b can be ultimately driven by the main indexing wheel 270, which cooperates with a ratchet mechanism 272, the purpose of which is to prevent rotation of the main indexing wheel 270 in the opposite direction.

[0104] Referring to Fig. 3c, it can be seen in turn that the main indexing wheel 270 can be rotated by means of the indexing lever 274 which rotates around the pivot point 275. Thus, actuation of the sheet drive assemblies 218a, 218b occurs as a result of the rotational movement of the indexing lever 274 to rotate the main index wheel 270, which accordingly results in transmission of the drive through the gearing 265 to the toothed surfaces 225a, 225b of bases 220a, 220b of both drive assemblies 218a, 218b of the sheet.

[0105] Referring now to Figures 3d to 3f, the shell portions, first 282 and second 284, of the dispenser housings 280 are applied to the drive unit 260. It can be seen that the mouthpiece 281 is jointly defined by the shell portions 282, 284. In Fig. 3e and 3f it can also be seen (only) that the movement of the cover 286 will result in the movement of the indexing lever mounted on the pin 273 of the indexing lever 274, such that the movement of the cover 286 will cause movement of the indexing lever 274, and thus in turn activate the mechanism for driving the drive units 218a, 218b of the sheet. Generally, in use, the patient moving the movable cover 286 provides means for propelling the sheet drive units 218a, 218b, and thereby shifting individual doses of drug disposed in the drug carrier slots.

[0106] The interaction of drug carriers and the drive unit of the dispenser of Figs. 3e and 3f can be better understood with reference to Figs. 4a and 4b.

[0107] Fig. 4a shows the medicament dispenser of Fig. 3e (a) having the top cover 282 and movable cover 286 removed (to better show the operation of the internal components); and (b) having the first drug carrier 302a disposed in the form of an elongated stripe, and showing insertion therein of the second drug carrier 302b in the form of an elongated stripe. Fig. 4b shows the drug dispenser of Fig. 4b with a second drug carrier 302b disposed therein in the form of an elongated strip.

[0108] More specifically, Figs. 4a and 4b show the base unit 360 of the drug dispenser. The first drug-containing blister strips 302a and 302b are adapted to be placed in the respective chambers, left 390a and right 390b of base unit 360. It will be appreciated that each blister strip 302a and 302b has the form shown in Fig. 1. Inside the dispenser, each blister strip 302a, 302b engages with a corresponding multi-nest indexing wheel 392a, 392b, and subsequent slots are thus directed toward the central opening station 393. The rotation of the indexing wheels 392a, 392b is optionally connected to each other (e.g., by means of a suitable gearing as shown in Fig. 3b). At the opening station 393, the top films 312a, 312b and base film 314a, 314b being parts of each of the strips 302a, 302b are separated from each other by peeling around the corner (not clearly visible). The resulting hollow base films 314a, 314b curl in respective receiving chambers 315a, 315b of the base. The base film anchors 317a, 317b anchors the end of each respective base film 314a, 314b in its chamber 315a, 315b.

[0109] The loop end 316a, 316b of each cover film 312a, 312b of each carrier 302a, 302b is received by a vertically projecting hook 358a, 358b of the respective drive of the torsion hub 350a, 350b. The internal design of each torsion hub drive 350a, 350b is as described with reference to Figs. 2a to 2k, or in an alternative embodiment as described with reference to Figs. 5a to 5h.

[0110] The function of each torsion hub drive 350a, 350b is to provide a roughly constant drive tension for each belt 302a, 302b during each of the entire belt length. In particular, each torsion hub 350a, 350b operates to compensate for changes in motive stress associated with an increase in the useful winding diameter of each hub 350a, 350b as worn cover films 312a, 312b gradually wrap around them. In this way, it is possible to maintain uniform alignment of each belt 302a, 302b over the entire length of the belt.

[0111] In use, the dispenser is initiated (usually by means of an actuating lever, for example, in the form of a movable cover 286, as shown in Figs. 3e, 3f) to actuate each drive of the torsion hub 350a, 350b bound with each carrier 302a, 302b, thereby causing its front seat to open due to peeling. Each steering hub 350a, 350b operates to provide all necessary drive compensation as described previously. To access the contents of the open sockets, the patient then inhales through outlet 381 (which is usually shaped as a mouthpiece or nosepiece). This creates a vacuum transmitted through the collector 383 to the open front seat of each strip 302a, 302b at the opening station 393. This, in turn, causes the drug powder contained in each of the open wells to be drawn through the common collector 383 to the outlet 381, and hence to the patient in the form of an inhaled dose of the combination drug. It will be appreciated that mixing of each drug component supplied separately occurs when transferring powder from each open well to outlet 381.

[0112] Figs. 5a to 5h are perspective views of details of a second sheet drive assembly.

[0113] Referring initially to Figs. 5a and 5b, the circular-shaped base 320 has a ratchet arm 321. A ring 323 having a first drive toothed surface 325 located on its outer periphery and a second toothed surface 327 located on its inner perimeter is pressed against the base 320. When fully compressed, it can be seen that the ratchet arm 321 of the base 320 meshes with the other (i.e. the inner) toothed surface 327 of the ring so that the ring 323 can only rotate in one direction relative to the base 320. The shaft 330 projects from this base 320.

[0114] Referring now to Figs. 5c and 5d, a torsion spring 340 having a lower arm 342 and an upper spring arm 344 is lowered onto a shaft 330 such that lower spring arm 342 fits into a retaining groove 324 of the base 320. The shaft 330 also has a projecting notch 334, whose function will be better understood from the description below.

[0115] Referring now to Figs. 5e and 5f, the hub 350 is lowered onto the shaft 330 so that it slides over the torsion spring 340. The upper arm 344 of the torsion spring 340 enters the spring arm retaining groove (invisible) made in the inner portion of the hub 350. The upper end 332 of the shaft 330 projects through the central hole 354 of the upper end 356 of the hub 350. It is also seen that hub 350 has a hook 358 adapted to receive the loop end of the sheet, as will be described in more detail below.

[0116] Referring now to Figs. 5g to 5h, the hub 350 is now rotated in a counterclockwise direction (in alternative embodiments, clockwise rotation is considered) by a specific rotation angle (in in this case about 90 °) relative to the base 320. It should be realized that since the torsion spring arms (invisible in Fig. 5g to 5h) connect to base 320 and hub 350 respectively, such a rotation causes the torsion spring to be tensioned. The range of specific rotation is selected so as to align the stepped wall (invisible) of the bottom of the hub 350 with the edge of the wall (invisible), which forms part of the retaining groove for lower spring arm 342.

[0117] The torsion spring (not visible in Figs. 5g to 5h) does not unwind from the tensioned state due to the ratchet interaction between the ratchet arm 321 of the base 320 and the inner toothed surface 327 of the ring 323.

[0118] One advantage of the form of the sheet drive assembly with the "ratchet hub" shown in Figs. 5a to 5h is that it allows for compensating for possible changes in spring tolerance. Such variations in spring tolerance often occur when springs are mass produced.

[0119] The second sheet drive assembly is now ready for use in a suitable drug dispenser.

[0120] Figs. 6a to 6d show attachment of the drug carrier end to hub 350 of the second sheet drive assembly of Figs. 5a to 5h.

[0121] Fig. 6a shows a second sheet drive assembly 318 disposed in the drive unit 360 of the respective drug dispenser, with the hook 358 of the hub 350 facing outward. In Fig. 6b, the loop end 316 of the drug carrier top sheet 312 (of the type shown in Fig. 1) is looped around the hub hook 358. In Figs. 6c and 6d, the sheet drive unit 318 rotates, thereby wrapping the top sheet 312 around hub 350 until loose is removed.

[0122] The drug dispenser according to the present invention is suitable for drug dosing, especially for the treatment of respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD), bronchitis and chest infections. Suitable drugs can therefore be selected from, for example, analgesics, for example, codeine, dihydromorphine, ergotamine, fentanyl or morphine; anti-angina preparations, e.g., diltiazem; antiallergic agents, e.g., cromoglycan (e.g., in the form of the sodium salt), ketotifen or nedocromil (e.g., in the form of the sodium salt); anti-infective agents, for example, cephalosporins, penicillins, streptomycin, sulfonamides, tetracyclines and pentamidine; antihistamines, e.g., metapyrylene; anti-inflammatory agents, e.g. beclometasone (e.g., in the form of a dipropionate ester), fluticasone (e.g., in the form of a propionate ester), flunizolid, budesonide, rofleponide, mometasone, e.g., in the form of the furoate ester), ciclesonide, triamcinolone (on example, in the form of acetonide) or 6-, 9a-difluoro-11 β-hydroxy-16a-methyl-3-oxo-17 α-propionyloxy-androst-1,4- acid S- (2-oxotetrahydrofuran-3-yl) ester thiocarboxylic diene 17β; cough suppressants, e.g., noscapine; bronchodilators, e.g., albuterol (e.g., in the form of the free base or sulfate), salmeterol (e.g., in the form of xinafoate), ephedrine, adrenaline, phenoterol (e.g., in the form of the hydrobromide), e.g. formoterol (e.g. in the form of fumarate), isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (e.g. in the form of acetate), reproterol (e.g. in the form of the hydrochloride), rimiterol, terbutaline (e.g. in the form of sulfate), isoetharin, tulobuterol or hydroxy-7- [2 - [[2- [[3- (2-phenylethoxy) propyl] sulfonyl] ethyl] amino] ethyl-2 (3H) -benzothiazolone; adenosine 2a antagonists, e.g. 2R, 3R, 4S, 5R) -2- [6-Amino-2- (1S-hydroxymethyl-2-phenylethylamino) -purin-9-yl] -5- (2-ethyl-2H-tetrazol-5-yl) tetrahydrofuran-3 , 4-diol (for example, in the form of maleate); α4 integrin inhibitors e.g. (2S) -3- [4 - ({[414 (aminocarbonyl) -1-piperidinyl] carbonyl} oxy) phenyl] -2 - [((2S) -4-methyl-2 - {[2- (2-methylphenoxy) acid acetyl] amino} pentanoyl) amino] propanoate (for example, in the form of the free acid or potassium salt), diuretics, for example, amiloride; anti-cholinergic agents, e.g., ipratropium (e.g., in the form of bromide), tiotropium, atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone or prednisolone; xanthines, for example, aminophylline, choline theophyllinate, lysine theophyllinate or theophylline; therapeutic proteins and peptides, for example insulin or glucagon; vaccines, diagnostic preparations and for gene therapy. It is clear to the person skilled in the art that, as required, the drugs can be used in the form of salts (e.g., alkali metal salts or amine salts or acid addition salts) or as esters (e.g., lower alkyl esters) or as solvates (e.g. hydrates) to optimize drug performance and / or stability.

[0123] Preferred drugs are selected from albuterol, salmeterol, fluticasone propionate and beclometasone dipropionate and salts or solvates thereof, for example, albuterol sulfate and salmeterol xinafoate.

[0124] Drugs can also be delivered in the form of combinations. Preferred formulations containing a combination of active ingredients contain salbutamol (e.g., in the form of the free base or sulfate salt) or salmeterol (e.g., in the form of xinafoate salt) or formoterol (e.g., in the form of fumarate salt) in combination with an anti-inflammatory steroid such as beclometasone ester (e.g., in the form of dipropionate) or fluticasone ester (e.g., in the form of propionate) or budesonide. A particularly preferred combination is the combination of fluticasone propionate and salmeterol or their salts (especially the xinafoate salt). A further particularly interesting combination is budesonide and formoterol (for example, in the form of a fumarate salt).

[0125] Typically, powdered drug particles suitable for delivery to the bronchial or alveolar lung region have an aerodynamic diameter of less than 10 microns, preferably less than 6 microns. Other particle sizes can be used if it is desired to deliver them to other parts of the airways, such as the nasal cavity, mouth or throat. The drug may be provided in the form of a pure drug, but more suitably, it is preferred that the drugs are provided with excipients (carriers) that are suitable for inhalation. Suitable excipients include organic excipients such as polysaccharides (i.e. starch, cellulose, etc.), lactose, glucose, mannitol, amino acids and maltodextrins, and inorganic excipients such as calcium carbonate or sodium chloride. The preferred excipient is lactose.

[0126] Powdered drug particles and / or excipient can be made by conventional techniques, for example, by micronization, milling or sieving. In addition, drug powders and / or excipients can be prepared with specific densities, particle size ranges or parameters. The particles may contain active agents, surfactants, wall forming materials or other ingredients deemed desirable by those skilled in the art.

[0127] The excipient may be included in the drug by well-known methods such as mixing, co-precipitation, etc. Mixtures of excipients and pharmaceutical agents are usually formulated to allow accurate measurement and dispersion of the mixture into dosage forms. A typical blend contains, e.g., 13,000 micrograms of lactose mixed with 50 micrograms of pharmaceutical agent, resulting in an excipient to pharmaceutical ratio of 260: 1. Dosage mixes with excipient to pharmaceutical ratios from 1000: 1 to 1: 1 can be used. At very low excipient to pharmaceutical ratios, however, the dose reproducibility of the pharmaceutical agent may be more variable.

[0128] It should be understood that the present disclosure is for illustrative purposes only, and the invention also includes modifications, variations, and improvements made thereto, within the scope of the claims.