MX2008007576A - Medicament dispenser - Google Patents

Abstract

There is provided a medicament dispenser device for the delivery of medicament powder from an open blister pocket (404a,b) of at least one blister pack (400a,b). The dispenser device comprises a housing (420) having an air inlet (470);enclosed by the housing, a dispensing mechanism (440, 448a,b) for the dispensing of medicament powder from an open blister pocket;and associated with the dispensing mechanism and in communication with the air inlet, a manifold (450). The manifold comprises a body, the body defining a chimney (452) having a chimney inlet (453) and a chimney exit (454a,b) for directing airflow (483) from said chimney inlet to said chimney exit;the body further defining a chamber (460) having a chamber inlet (473a,b) and a chamber exit (474), wherein the chimney exit and said chamber inlet lie side-by-side each other such that when said open blister pocket of said blister pack is positioned adjacent thereto said airflow may be directed from the chimney exit to the chamber inlet via the open blister pocket to entrain said medicament powder and enable transport thereof. In use, the airflow is drawn into the chimney of the manifold solely through the air inlet provided to the housing.

Description

MEDICATION DISPENSER Related Application The present application claims the priority of United Kingdom patent application No. 0 525 238.2 filed on 12 December 2005 and United Kingdom Patent Application No. 0 623 402.5 filed on November 23, 2006, the entire contents of which are hereby incorporated by reference.

Technical Field The present invention relates to a medicament dispensing device that incorporates a manifold for dispensing dry powder medicament, for example from a medicament carrier in the form of a blister pack. The collector promotes the effective release of the powdered medicament for inhalation by a patient, for example from a blister bag open to a dispenser nozzle, and, consequently, for its inhalation by a patient.

Background of the Invention The use of inhalation devices in the administration of medications, for example in bronchodilation therapy is well known. Such devices generally comprise a body or housing within which a medicament carrier is located. Known inhalation devices include those in which the medicament carrier is a blister containing a series of ampule bags for containment of the medicament in dry powder form. Such devices typically contain a mechanism for accessing a dose of medicament by opening one or more blister pouches. The mechanism by example comprises either perforation means or peeling means for removing a cover sheet from a base sheet of the blister. The powdered medicament is then released from the open ampoule bag (s) for the inhaled delivery to the patient. The inhalation devices of the type described above comprise an element, generally referred to as a collector, for guiding the flow of air towards one or more open blister pouches to release the dust contained therein; and, consequently, guiding this released powder towards a mouthpiece for inhalation by a patient. It will be appreciated that the characteristics of the collector are important both in ensuring the effective release of the powder and in guiding this released powder to the nozzle The Applicant now appreciates that the collector shape can affect the particle size characteristics of the released medicament powder , whose characteristics are known to be pharmaceutically important. In particular, the Applicant appreciates that the fine particle fraction can be influenced by the shape of the collector. As is known in the art, "fine particle fraction" or Fraction PF generally refers to the percentage of particles within a given dose of aerosolized drug which is of "breathable" size. It is desirable that the collector shape act in such a way that increase the Fraction PF of the released powder that is made available in the mouthpiece for inhalation by the patient In one aspect, the Applicant believes that the performance of the manifold (for example the fraction PF of drug powder dispensed) can be improved by directing, As much as possible all the air flow that enters the dispensing device during its use of inhalation to a collector, said collector communicates with an open blister pouch for the release of the powdered medicament contained therein. believes that it is beneficial that the housing of the dispensing device be arranged to provide an air inlet through which all the flow of air that enters the dispensing device for its use of inhalation, is directed towards the collector by a chimney component thereof. The use of such an air inlet to direct the air flow exclusively to the collector chimney provides good control over the air flow entering the collector, and in turn, is directed to the open blister pouch and therefore , allows a good consistency and a fine adjustment of collector performance.

SUMMARY OF THE INVENTION According to one aspect of the invention there is provided a medicament dispensing device suitable for dispensing powdered medicament from an open blister pouch of at least one blister, the dispensing device (a) comprising a housing; (b) said housing comprising an air inlet; (c) enclosed by said housing, a dispensing mechanism for dispensing powdered medicament from an open blister pouch of at least one blister that is received therefrom; and (d) associated with said dispensing mechanism and in communication with said air inlet, a manifold comprising (i) a body, (ii) said body defining a chimney having a chimney inlet and a chimney outlet for directing the chimney. air flow from said chimney inlet to said chimney outlet; (iii) further defining the body a chamber having a chamber inlet and a chamber outlet, (iv) in which the chimney outlet and said chamber inlet lie side by side so that when said chamber The open blister pouch of said blister is positioned adjacent thereto, said air flow can be directed from the chimney exit to the chamber inlet by the open blister pouch to draw said powdered medicament and allow the transport thereof in the flow of air from the chamber inlet to said chamber outlet, where during the inhalation use of the dispensing device by a patient, the air flow flows to the collector chimney only through the air inlet arranged in the housing . A suitable medicament dispensing device for the delivery of powdered medicament from an open blister pouch of at least one blister is provided. The medicament dispensing device comprises a housing, which can have any suitable shape or shape. A preferred form is that of a shell-like housing formed by a joint assembly of two shell halves, which can either be articulated or alternatively, be completely separable one half of the other. The housing is formed from any suitable material, but more typically comprises a plastic polymeric material that is relatively robust but is also easily constructed by a volume manufacturing process. The accommodation is provided with an air inlet. This typically takes the form of a hole or holes of appropriate shape and dimension disposed in the wall of the housing. The air inlet is appropriately positioned to be placed in a position that would not typically be covered or blocked by a user's fingers and / or thumb during normal use. The air inlet is appropriately covered at least partially by a protective grid or other feature which acts to prevent blocking and / or minimize the undesirable entry of dust and other particulate contaminants thereto. Enclosed by the housing, a dispensing mechanism for the dispensing of powdered medicament from an open blister pouch of at least one blister which is received therefrom is provided. The details of the appropriate dispensing mechanisms are provided by the subsequent description. Associated with the dispensing mechanism and in communication (ie fluid communication / air flow) with the air inlet, a manifold is provided. The manifold comprises a body that is generally dimensioned and shaped to be received by a medicament dispensing device, of which it typically comprises a constituent part. The manifold itself may either be constituted by a single component, integral or sub-assembly or part of an adjacent component, and is typically formed as a molded part. In aspects, the manifold is either integral to or separable from the other components of the medicament dispensing device. In one aspect, the manifold is arranged as a pressure-adjusting component separable to the medicament dispensing device and the manifold and / or the medicine dispensing device is provided with press fit features (eg located on the body of the dispensing device) to allow this mounting mode. Suitably, the manifold is arranged to be received by a medication dispensing device at a location that is intermediate between a nozzle for the delivery of medicament in inhaled form by a patient, and an opening station, in which an open bleb bag of the blister is presented to the collector (that is, in which you can access its content of medication and drag it). Suitably, the manifold is provided with snap-fit features to allow its snap-fit to the nozzle to form a manifold and nozzle subassembly mounted under pressure. The collector body defines a chimney that has a chimney inlet and a chimney outlet. In operation, air is drawn through the chimney inlet (for example as a result of patient inhalation) to create an air flow inside it. The chimney acts to direct this flow of air from the chimney inlet to the chimney outlet. The collector body also defines a camera that has a camera input and a camera output. The air and the powdered medicament dragged inside (see below) can be dragged through the chamber inlet to the chamber outlet. A nozzle is generally located adjacent to the chamber outlet. In a particular aspect, this part of the body defining the chamber outlet and nozzle comprises a common component. The chimney outlet and the chamber inlet lie one next to the other (i.e., adjacent or close) in such a way that When said open blister pouch of said blister is positioned adjacent thereto, the air flow can be directed from the chimney outlet to the chamber inlet through the open blister pouch to entrain the powder medicament content thereof. . The transport of the medicament particles thus entrained is therefore possible in the air flow from the chamber inlet to the chamber outlet. The manifold may define more than one chimney outlet and chamber inlet and this will typically be carried out where the manifold is intended to be used with a medication dispensing device to dispense a medicament from more than one open blister pouch at a time . Typically, a chimney outlet and a chamber inlet that are side by side will be provided to dispense powder from each open blister pouch. In one aspect, the manifold of the present specification is suitable for use in a medicament dispensing device for dispensing powdered medicament from an open blister pouch of each of several blisters, the manifold comprising various delivery couples of chimney and chimney inlet, each pair being associated with an open blister pouch of one of said various blister packs. Thus, for example, in a preferred medicament dispensing device of the present specification, arranged to dispense powder from a pair of open blister pouches, each of the pair associated with a single elongated blister strip, the manifold will be provided of a pair of chimney exits and associated chamber entrances, each resting side by side. The medicine dispenser provides for the flow of air to flow into the manifold stack only through the air inlet arranged in the housing. That is to say, all the air that flows to the collector does it through the air inlet and the chimney of the collector. In this way, during its use, the patient inhales through the mouthpiece, which creates a negative pressure in the collector, which causes the air to be attracted from the outside of the dispensing device through the air inlet and towards the collector chimney. At least part of that air flow is then directed from the chimney outlet to the chamber inlet by the open blister pouch to entrain the powder drug content thereof. Preferably, the air inlet provides the single entry point for the flow of air to the medicament dispensing device, and particularly to the open blister pouch of the blister, during the use of inhalation of the dispensing device by a patient. In this way no other air inlet or other air inlet point is provided to the housing and the housing itself provides a relatively air tight barrier for the entry of outside air into the interior by any other means. In one aspect, all of the air flow flowing through the air inlet and into the chimney of the sump is then directed through the chimney outlet to the open blister pouch. In other preferred aspects, however, the geometry of the collector is arranged in such a way that only a proportion of the total air flow entering the collector through the air inlet to the stack thereof is directed by the chimney outlet. towards the open blister pouch. Preferably, one or more purge holes are disposed between the chimney and the chamber so that the flow of purge air can be directed into the chamber to impact disruptively against the air flow carried by the entrained powdered medicament. Suitably, from 3% to 50%, preferably from 5% to 25%, (for example approximately 20%) of the flow of toral air entering the manifold through the air inlet to the chimney thereof is directed by the chimney outlet towards the open blister pouch and, consequently, through the chamber inlet towards the chamber. That is, from 97% to 50%, preferably from 95% to 75%, (for example approximately 80%) of the total air flow is directed through one or more purge holes to the chamber. The present manifold is suitable for use in a medication dispensing device in which the patient breathes to create the air flow and purge the flow of air through the manifold. The manifold and the drug dispensing device of the present specification are designed to be suitable for use by a patient (eg asthmatic) with a relatively poor respiratory capacity. A typical asthmatic patient can achieve a flow rate of about 30 to 100 liters / minute through a drug dispensing device. Typically, the collector provides a resistance to air flow of 1 to 5 kPa (for example 2-3 kPa) for a typical air flow entering the chimney of 60 liters / minute, of which about 10% of the air flow It is directed through the open blister pouch. The air flow that enters the chimney can also vary, typically from 30 to 100 liters / minute. It will be appreciated that in operation, the pressure drop and the flow velocity that can be achieved by a patient depends both on the level of resistance to the air flow of the manifold and / or the medication dispensing device and on the respiratory capacity (respiratory effort). ) of the patient. As will be appreciated in the following description, the vent hole (s) disposed therein can in particular be used to control the total resistance to the air flow of the manifold. The resistivity of the air flow of a particular manifold and / or drug dispensing devices can be discovered by dividing the square root of the pressure drop (in kPa) by the flow rate (in liters / minute). The low resistivity of the air flow of the manifold and / or the medication dispensing device is generally preferable because it allows the patient to take a deep breath and therefore transport the medicament particles (distributed from the dispensing device) to the lungs., the cross-sectional area of the air inlet provided to the housing of the medicament dispensing device is greater than (eg, at least one and a half times, preferably twice) the cross-sectional area of any part of the manifold, whose air incoming will collide (downstream) against the collector. Thus, the cross-sectional area of the air inlet is appropriately greater than any of the cross-sectional area of the chimney, the total cross-sectional area of the chimney outlet and one or more purge holes; and the cross-sectional area of the chamber. The rationale for this is that the air inlet can not therefore act to limit or otherwise affect the nature of the air flow through the dispensing device and thus, the entire control of the air flow (and air pressure). air, etc.) is a result of the geometry and arrangement of the collector (including the selection of cross-sectional areas for any collector part). It will be appreciated that the exact orientation of the chimney outlet and the chamber inlet will be determined to some extent by the shape of the blister pouch, and the desired function of entraining powdered medicament particles in the airflow directed towards the bag. In one aspect, the open blister pouch has a generally elongated oval profile and the chimney outlet and chamber inlet lie side by side, and in operation are positioned above the opposite ends of the blister pouch profile open oval elongated. It will also be appreciated that the shape and dimensions of the chimney outlet and the chamber inlet will be determined to some extent by the shape of the blister pouch, and the desired function of entraining medicament particles in the air flow through of the bag. It has been found that reducing the cross-sectional area of the chimney outlet and the chamber inlet can improve the performance of the PF fraction at the expense of greater resistance to airflow and potentially a reduction in the discharge performance of the bag. In one aspect, the chimney outlet and the chamber inlet define an essentially circular profile and have a diameter of 1 -7 mm, particularly 2-5 mm. Other profile shapes for the chimney exit and the chamber entrance are also considered including the oval, rectangular, rectangular with rounded edges and increasingly. Suitably, the manifold chimney of the present invention is arranged to create turbulence in the air flow in the open blister pouch. That is, the chimney is arranged such that in use, turbulent air flow occurs in the open blister pouch. It has been found that such a turbulent air flow favors the entrainment of the powdered medicament content of the open blister pouch, and thus favors the emptying of the pouch from its powdered medicament content. In one aspect, the turbulence occurs as a result of the creation of a shear resistance, which favors the entrainment of the powdered medicament by the air flow. Shear strength is generally defined as a gradient of average velocity normal to the direction of air flow. In this way, a region of high shear strength ("high shear") is one in which there is a relatively large velocity gradient over a relatively short distance. The presence of such turbulence can be particularly beneficial where the powdered medicament comprises non-cohesive powder components (for example, joins that is not sticky or only loosely associated, for example not agglomerated). The well-known Carr index can be used to quantify the cohesion of a particular powder for distribution by the manifold and the medicament dispensing device of the present invention. The procedures for measuring the Carr index are described in the following references: Carr, R.L. (1965) Chem. Eng. 72 (1) page 162; Carr, R. L. (1965) Chem. Eng. 72 (2) page 69; and Pharmaceutics: The Science of Dosage Form (1988) Ed. Aulton, M. E, Churchill Livingstone, New York. In one aspect of the present invention, the turbulent flow is created in the open blister pouch by providing various chimney outlets to the chimney, each of which directs the air flow to the open blister pouch. In a particular aspect, the various chimney outlets are positioned so that in use, several jets of air flow are directed towards each other to produce a turbulence interaction (for example high shear). The various chimney outlets (and therefore, the various air flow jets) are properly positioned at an angle (?) To each other where? it is typically 150 ° to 30 °, preferably 120 ° to 60 °. In another aspect of the present invention, turbulent flow is created in the open blister pouch by forming the chimney and / or chimney outlets to produce a non-linear air flow. In a particular aspect, the chimney and / or chimney outlets are shaped to produce a helical airflow (e.g., vortex type) that is inherently turbulent. In another aspect of the present invention, an obstacle is positioned towards the chimney and / or chimney outlet to disruptively create a non-linear air flow. In a particular aspect, a cross member or divider (eg in the form of a separating blade) is provided towards the chimney and / or at the chimney outlet to interrupt the air flow and produce turbulent regions of high shear strength. Suitably, the chimney of the manifold of the present invention is arranged to create regions of acceleration or deceleration in the air flow in the open blister pouch. That is, the chimney is arranged so that, in use, the flow of acceleration or deceleration air is present in the open ampule bag. Such a flow of accelerating or decelerating air (turbulent or not) favors the entrainment of the powdered medicament content of the open ampoule bowl, and thus favors the emptying of the bowl of its powdered medicament content. The exit of chi menea and the chamber entry may comprise one or more simple openings (ie, holes) or alternatively, in the aspects, some features may be provided including a "crossbar" (for example cruciform) provided in the opening (s) of one or both of them.

Appropriately, the chimney and the collector chamber are arranged side by side or one above the other in order to favor the requirements for (i) the chimney outlet and the chamber inlet to lie side by side and (ii) so that one or more purge holes are disposed between the chimney and the chamber, as is now described in more detail. The collector of the present invention provides that the medicament in entrained powder is transported by the chamber through the air flow from the chamber inlet to the chamber outlet. One or more drain hole (or passages / channels) are preferably disposed between the chimney and the chamber so that the flow of purge air can be directed towards the chamber to impact disruptively against the flow of air carried by the medicament powder dragged. The presence of one or more purge holes thus positioned improves the overall performance (eg, PF fraction performance) of the collector. In particular, it is beneficial for the purge air flow to promote the disintegration (eg, deaggregate or de-agglomerate) of the powdered medicament entrained in the chamber. In particular, exposing the entrained powdered medicament to regions of differential force that occur as a result of the introduction of the purge air flow from the stack to the chamber favors the promotion of the desired disintegration of the powder in the chamber. The promotion of such disintegration can be particularly beneficial where the powdered medicament comprises cohesive powder components (for example one comprising particles that tend to associate with another or one in which the particles are agglomerated). Where one or more purge holes are arranged, it can be seen that in use, the total air flow entering the manifold stack is 'separated' towards the portion that is directed to the open blister bag to entrain the medicament. powder and the portion that is directed through one or more of the purge holes as purge air. The collector can be fine-tuned to determine the percentage of total air flow that constitutes each of the 'separated' portions and thus allow fine tuning of collector performance. Although collectors of the prior art (including those described by the above patent publications WO98 / 30262, WO98 / 1 1929, WO 02/104244, US-A-2,587,215, US-A-5,383,850, EP-A-1, 106 , 196, WO 94/08552, WO 94/1 1044, US-A5,590,645 and US-A-5, 113,855) have been described as comprising purging holes in a chamber or nozzle element, all collectors of the art above are intended in use, to expel purge air through an air inlet that communicates directly with the external environment (ie, from the outside). On the contrary, the manifold of the present invention provided with one or more purge holes between the chimney and the chamber requires that all the air flow to the collector be by the chimney, which acts to 'separate' the air flow total in one air part 'directed from open blister (by the chimney outlet and the chamber inlet) and a part of' purge 'air (by one or more purge holes to the chamber). A good control over the amount of purge air and the percentage thereof (with respect to the total air flow entering the stack) is therefore possible. Suitably, one or more purge holes are arranged in a wall that is common to (and acts as a boundary between) the chimney and the chamber. Suitably, the chimney and the chamber share a common wall and at least one of, preferably all of, one or more of the purge holes are disposed to said common wall. One or more purge holes typically have an overall cross-sectional area (ie, the cross-sectional area of all the purge holes added together) of 1 -35 mm2, preferably 10-30 mm2, more preferably 15- 25 mm2. One or more purge holes can define any appropriate profile including the oval, circular, D-shaped and elongated slot. In one aspect, one or more purge holes are circular or ovular and each purge hole has a diameter of 1 -7 mm, preferably 2-5 mm. In another aspect, one or more purge holes are D-shaped and have a maximum diameter of 1 -10 mm, preferably 3-7 mm. In another aspect, one or more purge holes comprise or consist of elongated slots and have a length of 1 -20 mm, preferably 3-10 mm and a width of 0.5-3 mm, preferably 0.7-2 mm. In a particular aspect, two elongated slot-shaped purge holes arranged in parallel are disposed between the chimney and the chamber. Preferably the parallel elongated slot-shaped purge holes are arranged to be parallel to the air flow within the chamber. In one aspect, one or more purge holes are disposed adjacent (i.e., proximal) the chimney outlet and / or the chamber inlet. In another aspect, one or more purge holes are spaced from the stack inlet / chamber inlet. Typically, the spacing of one or more purge holes of the chamber inlet is equivalent to at least 10%, preferably at least 20%, more preferably at least 30% of the length of the chamber measured from the chamber inlet at the exit of the camera. In one aspect, one or more of the purge holes are directed towards a wall of the chamber, thereby creating a raised shear region close to the wall and causing the particles to collide against said wall. Preferably, the overall geometry of the chamber is arranged to direct the air flow to these high shear regions and / or to produce collisions against the wall. An additional advantage of directing the purge air to the collector walls is to prevent the deposition of medicament particles thereon. Where various purge holes are arranged, they are appropriately directed towards one another so that the resulting purge jets interact with each other to create high shear regions. Preferably, the total geometry of the chamber is arranged so as to direct the air flow to these high shear regions. Suitably, in use, one or more purge holes direct one or more air jets to impact against at least one internal surface of the chamber to create at least one elevated shear zone therein, greater than 3 Pa at a flow rate of air of 60 liters / minute for the air entering the chimney. Suitably, in use the powder medicament of the bag is directed towards at least said elevated shear zone within the chamber to disintegrate any agglomerated particle components thereof. Suitably, in use, at least one elevated shear zone acts to reduce deposition of dust on at least said inner surface of the chamber. It will be appreciated that the provision one or more purge holes of this type also result in reduced air flow resistance because a proportion of the air flow (as attracted to the chimney) is not removed through the open blister pouch. . The provision of purge holes can, therefore, potentially affect the effectiveness of emptying the open blister pouch of its medicament content. One must therefore achieve a compromise between the creation of regions of accelerating air flow by providing one or more purge holes (good for the disintegration of dust in the chamber) and the reduction of airflow resistance (and that Potentially affects the emptying of the bag). As a rule, the airflow resistance of the collector should not be reduced below a level at which the emptying of the bag is compromised at a minimum flow rate of 30 liters / minute for the air entering the chimney. Typically, the collector of the present invention is arranged in such a way that from 3 to 50%, preferably from 5 to 25% (for example approximately 20%) of the air flow entering the chimney inlet is directed by the chimney outlet towards the open blister pouch. The rest of the air flow is therefore directed towards the open blister pouch and instead passes through one or more purge holes to the chamber. Generally speaking, for a cohesive powder, it is desirable to direct less air flow through the bag than for a very cohesive powder. In aspects of the present invention, the dimension and / or location of any inlet, outlet and / or one or more of the manifold bleed holes is adjusted to achieve the desired level of air flow through the bag and / or the resistance to air and / or shear towards the collector, in use. It will be appreciated that such adjustment may take into account the cohesion or otherwise of the powdered medicament that is distributed through the collector. Additionally, the disintegration of the powder in the chamber can, in addition, be promoted if the geometry and shape of the chamber are themselves arranged, to create regions of high differential force (for example high shear). The appropriate regions of high shear can be created if the diameter and / or the shape of the chamber varies appropriately along its length (ie, along the path of the air flow it defines) so that the flow of air and the entrained dust that flows through it tend to hit the walls of the chamber. Such trips against walls are always in high shear regions (ie, high velocity or near air flow at low air flow velocity) because in the wall itself the velocity of the air flow is effectively zero. In another aspect, the disintegration of the powder can also be promoted in the chamber if the chamber is arranged so as to create the regions of air flow of acceleration or deceleration therein. That is, dust disintegration is promoted if an airborne and entrained dust encounters the region of accelerating or decelerating air flow flowing through the chamber. Preferably, the overall geometry of the chamber is arranged to direct the flow of air carried by the entrained particles into these regions of accelerating air flow. It will be appreciated that, in use, the presence or absence of accelerating or decelerating airflow in the manifold of the present invention may depend either on the patient's inhalation profile or on the manifold geometry. Thus, a patient inhalation profile involving a change from slow inhalation to rapid inhalation will result in a 'patient-created' region of accelerating airflow. On the other hand, a manifold geometry that (for any patient inhalation profile) results in regions of slowly moving airflow that is created adjacent to fast-moving airflow regions of how the result a desired region of accelerating air flow. Alternatively, the manifold may be provided with features such as fins or valves that open in response to a particular airflow pressure thereby creating zero flow "acceleration" (i.e., fin or valve closed) in the permitted flow (ie, fin or valve open). Suitably, in use, the manifold is arranged to modify the effect of a user inhalation profile to increase the acceleration experienced by the powder when it is aerosolized in the ampoule bag. Suitably, in use, the manifold is arranged to modify the effect of a user inhalation profile to increase the acceleration experienced by the powder as it travels through the chamber from the blister pouch to the patient. The improved propensity for a given patient inhalation profile results in regions of accelerating air fl ow being able to be created in an appropriate manner if the cross-sectional area (e.g., the diameter) of the chamber is reduced in the direction of flow. It will be appreciated that a smaller cross-sectional area will mean that the air has a higher velocity for a given flow velocity. The acceleration for a given profile of navigation will therefore be proportionally greater. The appropriate regions of acceleration or deceleration air flow can also be created in the collector if the cross-sectional area (eg, diameter) of the chamber is arranged to vary in diameter, for example to narrow along its length. length (ie, along the path of the air flow it defines) so that the air flow and the entrained dust flowing through the same collides with a narrower cross-section or alternatively widens along of its length (i.e., along the deflected air flow path) so that the air flow and entrained dust flowing through it collides against a wider cross section. It will be appreciated that any reduction of the cross-sectional area of the chamber will result in increased resistance to airflow, and therefore can potentially affect the effectiveness of emptying the open blister pouch of its medicament content. It is therefore necessary to achieve a compromise between the creation of regions of accelerating air flow by reducing the cross-sectional area of the chamber (good for the disintegration of dust) and increasing resistance to airflow (and potentially affecting the emptying the bag). In one aspect, the diameter of a circular profile chamber narrows approximately from 14-16 mm at the entrance end of the chamber to approximately 5-8 mm at the exit end of the chamber. In another aspect, the diameter of a chamber is approximately 5-7 mm along its entire length (opposite a conventional diameter of approximately 14-16 mm). In another aspect, the disintegration of the powder can also be promoted in the chamber if the chamber is arranged in such a way that mechanical obstacles are created inside it. That is to say, the disintegration of dust is promoted if an air flow (entrained dust) collides with mechanical obstacles flowing through the chamber. Appropriate mechanical obstacles that may be arranged in the chamber comprise or consist of deflectors, propellers, vanes, vanes and venturi shapes. Alternatively, the camera itself may be configured with features (e.g. indentations or defined surface protuberances) that provide mechanical obstacles. The performance of the collector can, in addition, be improved if the collector is arranged to delay the emptying of the powdered medicament content of the ampoule bag. In one aspect such delay is achieved by reducing the amount of air flowing through the open blister pouch. Such reduction should not, however, be too pronounced since insufficient air flow through the bag can prevent complete emptying of the medicament content from the open blister pouch. Such reduction of air flow through the open blister pouch is achieved by providing the manifold with one or more purge holes positioned to "deflect" the air flow from the open blister pouch. The performance of the manifold of the present invention can be improved where the manifold is arranged to delay the emptying of the powdered medicament contents from the ampoule bag until regions of differential force are created in the chamber (e.g. acceleration) capable of producing the disintegration of dust. If the blister bag is emptied too soon of the powder to be disintegrated it will pass through the high differential force zones before they are fully established, therefore the delay of emptying the blister bag will improve the performance of the manifold ensuring that most of the dust will collide with a high shear region. Properly, the manifold of the present invention is arranged to retard the emptying of the powdered medicament contents from the blister pouch until the patient achieves a predetermined flow rate through the manifold chamber (i.e., not only through the blister bag). Although the value for the predetermined flow rate can be made by fine adjustment, it is generally desirable to have a value between 5 to 45 liters / minute, preferably 20 to 30 liters / minute. Desirably, the collector of the present invention acts globally to improve the uniformity of the dose of medicament distributed therein. Desirably, the collector of the present invention acts globally to increase the Emitted Dose (DE) of powdered medicament that is available at the chamber / nozzle outlet for inhalation by the patient. The DE is generally measured by collecting the total amount of powdered medicament emitted from the dispensing device for example, using a dose sampling apparatus such as a Dose Uniformity Sampling Apparatus (AMU). The ED can also be expressed as a percentage (% of DE) of the measured dose (DM) contained to the blister (s) from which the powdered medicine is released. Thus, in this case, the% DE is calculated as (DE / DM) x 100%. It is desired that the% DE is at least 95% by weight, preferably more than 98% by weight. Desirably, the collector of the present invention also acts to increase the PF fraction of the powdered medicament that is available at the chamber / nozzle outlet for inhalation by the patient. The term "fraction of fine particle of emitted dose" or Fraction PF (DE) refers to the percentage of particles within a Dose Issued of aerosolized drug that is "breathable" in size, compared to the total emitted dose. A range of particle size of 1-6 μm is generally considered as being of "breathable" size. The Fraction PF (DE) can thus be calculated as a percentage of the Emitted Dose (DE). Thus, in this case, Fraction PF (ED) is calculated as (FPF / DE) x 100%. It is desired that the Fraction PF (ED) be at least 25% by weight, preferably more than 30% by weight of the Dose.

Emitted from available particles in the chamber / nozzle outlet.

The PF Fraction can also be defined as a percentage of the measured dose (DM) contained in the particular blister pack (s) from which the powdered medicament is released. Thus, in this case, Fraction PF (DM) is calculated as (FPF / M D) x 100%. It is desired that the PF (DM) Fraction is at least 25% by weight, preferably more than 30% by weight.

The collector of the present invention is typically disposed (as a constituent part thereof) in a medicament dispensing device that is arranged to receive a blister pack having one or more ampoule bags containing medicament in dry powder form. In one aspect, the blister comprises multiple blister pouches for the containment of the medicament product in dry powder form. The blister pouches are typically arranged in a regular manner to facilitate the release of the medicament therefrom. Blister pouches can have any suitable shape including those with a square, circular, ovular or rectangular profile. The particular shape, which includes configuration and cross-sectional area, of the blister pouch affects the properties of the air flow, and in particular, the resistance to airflow and the pressure drop experienced in the open pouch when a patient inhaled through the manifold of the present invention. By way of example, a typical dose of powdered medicament in a blister pouch is 17 μl. If the blister bag were in the shape of a sphere, to accommodate this dose, it would have a radius of 1.7 mm and a cross-sectional area of 8.0 mm2. A flow of 60 I / min through an area of 8 mm2 is equivalent to an average speed of 125 m / s. The pressure drop due to this flow will be approximately equal to: (where p = air density = 1.3kg / m3, V = average speed = 125m / s and K = a geometric factor). For a sudden contraction of a broad cross section to 8.0 mm2, K = 0.5 (approx.) So that the fall of For a single input-output system (as above) the pressure drop at 60 liters / minute would be 61.2kPa. the resistivity would be 0.130 (kPa) 0 5 minute / liter and the flow for a pressure drop of 2kPa would be 1 1 liters / minute (18% flow). For a blister bag suitable for use with the well-known Diskus device (trademark), the resistivity would be approximately 0.15 (kPa) 0 5 minute / liters and the flow for the pressure drop of 2kPa would be 9.4 liters / minute (16 % flow of 60 liters / minute). In one aspect, the multidose blister comprises various ampules generally arranged in a circular fashion on a disc-shaped blister. An example of a suitable medicament dispensing device for dispensing powdered medicament from a disc-shaped blister is the well-known Diskhaler device (trademark) sold by GlaxoSmithKIine Pie. In another aspect, the blister is of elongated shape, comprising, for example, a strip or a ribbon. Preferably, the blister is defined between two members peelably attached to each other. United States Patents Numbers. 5,860,419, 5,873,360 and 5,590,645 in the name of Glaxo Group Ltd describes medicament packages of this general type. In this aspect, the device is usually provided with an opening station comprising peeling means for separating the members to access each dose of medicament.

Suitably, the medicament dispensing device is adapted for use where the separable members are elongated sheets defining a plurality of medicament containers spaced along their length, the device being provided with indexing means to in turn index each container . More preferably, the medicament dispensing device is adapted to be used where one of the sheets is a base sheet having a plurality of bags in its interior, and the other of the sheets is a cover sheet, defining each bag and the adjacent part of the sheet. the cover sheet a respective container, the medicament dispensing device comprising actuating means for separating the cover sheet and the base sheet at the opening station. An example of a drug dispensing device of this type is the well-known Diskus device (trademark) sold by GlaxoSmithKIine Pie. In one aspect, the ampule-shaped medicine container comprises (a) a base sheet in which the ampoules are formed to define bags therein containing an inhalable dry powder medicament formulation.; (b) a cover sheet that can be sealed against the base sheet in the region of the ampoules and mechanically separated from the base sheet to allow the release of said inhalable dry powder medicament formulation, wherein said base sheet and / or said The cover sheet has a laminar structure comprising (a) a first layer of aluminum foil, and (b) a second layer of polymeric material having a thickness of 10 to 60 microns. The base and cover sheets are typically sealed to one another over their entire width except for the front end portions where they are typically not at all sealed to one another. In this way, the separate end portions of the base and cover sheets are present at the end of the strip. Suitably, the polymeric material has a water vapor permeability of less than 0.6 g / (100 inches2) (24 hours) (mil) at 25 ° C. The water vapor permeability is appropriately measured by the ASTM test method no. ASTM E96-635 (E). Suitably, the polymeric material comprises a matepal selected from the group consisting of polypropylene (for example in oriented or fused form, standard or metallocene); polyethylene (for example in the form of high, low or intermediate density), polyvinyl chloride (PVC); polyvinylidene chloride (PVDC); polychlorotrifluoroethylene (PCTFE); cyclic olefin copolymer (COC); and cyclic olefin polymer (COP). Suitably, the cover sheet comprises at least the following successive layers: (a) paper; attached to (b) plastic film; attached to (c) aluminum foil.

The aluminum foil is typically coated with a layer (e.g., heat seal varnish, film or extrusion coating) to bond the material of the base sheet. The thickness of each of the layers of the covering sheet can be selected according to the desired properties but typically it is of the order of 5 to 200 microns, particularly of 1 to 50 microns. The plastic layer is in one aspect, appropriately selected from polyester (monoaxial oriented or biaxial oriented), polyamide, polypropylene or PVC. In another aspect the plastic film is an oriented plastic film, appropriately selected from oriented polyamide (OPA); oriented polyester (OPET); and oriented polypropylene (OPP). The thickness of the plastic layer is typically from 5 to 40 μm, particularly from 1 to 30 μm. The thickness of the aluminum layer is typically from 1 0 to 60 μm, particularly 15 μ to 50 μm such as 20 to 30 μm. In the aspects, the paper layer comprises a layer of paper / extrusion layer, optimally laminated to the aluminum. In a particular aspect, the cover sheet comprises at least the following successive layers: (a) paper; bonded to (b) polyester; attached to (c) aluminum foil; which is coated with a heat-sealed varnish to join the base sheet. The thickness of each layer can be selected according to the desired properties but typically it is of the order of 5 to 200 microns, particularly of 10 to 50 microns. The bond can in the aspects be provided as an adhesive bond (for example solvent-based adhesive in which the solvent is organic or water-based), adhesive bonding without solvent; extrusion laminated joint, or thermocaladder. Suitably, the base sheet comprises at least the following successive layers: (a) oriented polyamide (OPA), adhesively bonded to (b) aluminum foil, adhesively bonded to (c) a third layer of thickness from 10 to 60 microns comprising a polymeric material. The polymeric material preferably has a water vapor permeability of less than 0.6 g / (100 inches2) (24 hours) (mil) at 25 ° C. The third layer will be bonded with the cover sheet, which is usually treated with a heat seal varnish. The thickness of each non-polymeric layer of the base sheet may be selected according to the desired properties but is typically of the order of 5 to 200 microns, particularly 20 to 60 microns. According to the invention, the thickness of the polymeric layer is selected to reduce the entry of moisture, and is from 10 to 60 microns, particularly from 25 to 45 microns, preferably from 30 to 40 microns. Suitably, the polymeric material is selected from the group consisting of polypropylene (in oriented or molten form, standard or metallocene); polyvinyl chloride (PVC); polyethylene (in the form of high, low or intermediate density), polyvinylidene chloride (PVDC); polychlorotrifluoroethylene (PCTFE); copolymer cyclic olefin copolymer (COC); and cyclic olefin polymer (COP). Other layers of material are optionally present. Various known techniques can be used to join the cover sheet to the base sheet and thus seal the blisters. Such procedures include adhesive bonding, radiofrequency welding, ultrasonic welding and heating rod welding. The base sheet of the present invention is particularly suitable for forming by cold forming processes which are carried out at lower temperatures than conventional processes (for example close to room temperature). Such cold forming processes are of particular utility where the medicament or medicament formulation to be contained within the ampoule is thermosensitive (eg degrades or denatures upon heating). The blister may be appropriately received by a medicament dispenser comprising the manifold of the present invention which also comprises a housing for receiving the package. In one aspect the medication dispenser has a unitary shape and the housing is integral with it. In another aspect, the medication dispenser is configured to receive a refill cartridge and the housing is part of this refill cartridge. Suitably, the interior of the housing is shaped, or alternatively provided with specific guiding features, to guide the ampule-shaped medication container appropriately into the housing. In particular, the guidance ensures that the blister is properly positioned to interact with the internal mechanisms (eg, indexing and opening mechanisms) of the housing. Suitably, the drug dispensing device has an internal mechanism for dispensing the various doses of dry powder medicament carried by the blister packs for administration to the patient (eg, by inhalation).

Appropriately the mechanism comprises; (a) a receiving station to receive the blister; (b) a release station for releasing a different dose of medicament from an ampoule of the blister upon receipt by said receiving station; and (c) an indexing station for individually indexing the different medicament doses of the blister pack, wherein the collector of the present invention is positioned to be in communication with the dose of drug releasable by said release station. The mechanism comprises receiving means (for example a receiving station) for receiving the blister. The mechanism further comprises releasing means for delivering a different dose of medicament from a blister of the blister upon receipt by the receiving station.

The receiving means typically comprise means for mechanically separating the blister strip. A collector of the present invention is positioned to be in communication with the different doses of powdered medicament released by said release means. The distribution of the medicament thus released to the patient for his inhalation by the same, is preferably carried out through a single outlet which communicates with or forms a solidary part with the collector. The output can have any desired shape. In one aspect, it has the shape of a mouthpiece for insertion into a patient's mouth; and in another it has the form of a cannula for its insertion towards the nasal bag of a patient. The mechanism also comprises indexing means for indexing the individual ampoules containing medicament doses of the medicament package in the form of an ampoule. Said indexing typically occurs sequentially, for example by accessing the dose portions sequentially spaced along the length of the ampule-shaped medicine container. Optionally, the medication dispenser also includes counting means for counting each time a dose of medication other than the ampule-shaped medication container is indexed by said indexing means. In one aspect, the counting means are arranged to count each time a dose of medication other than the drug carrier is indexed by said indexing means. Suitably, the indexing means and the counting means are coupled di rectly or directly (for example by a coupling) with each other to allow counting of each indexing. Suitably, the counting means are provided with (or communicated with) a viewer to show the patient the number of remaining doses to be taken or the number of doses taken. In a preferred aspect, the medicament dispenser takes the form of a dispenser for use with a ampule-shaped medicine container of the present invention having multiple distinct pockets for containing doses of inhalable medicament, wherein said pockets are spaced apart along the length of and defined between two separable sheets affixed to each other, said dispenser having an internal mechanism for dispensing the doses of medicament contained within said medication package, said mechanism comprising, (a) a station of opening for receiving a bag from the medication container; (b) a peeler positioned to engage a base sheet and a cover sheet of a bag that has been received at said opening station to peel off such base sheet and such cover sheet, to open such a bag, Including said peel separation means a cover actuator for separating a cover sheet and a base sheet from a bag that has been received at said opening station; and (c) an indexing station for individually indexing the various pouches of the medicament package, wherein the collector of the present invention is positioned to be in communication with an open pouch through which the dose of medicament can be released from such an open bag. Properly, the indexing means comprise a rotary index wheel having bolts in its interior, said index wheel being able to be coupled to a package of medicament in use with said medicament dispenser so that said bags receive each respective bag of the base plate of a blister strip in use with said medicament dispenser. According to another aspect of the present invention there is provided a medicament dispenser comprising (for example loaded with) at least one blister containing dry powder medicament of the invention. The collector of the present invention has been described above in terms of its use with a medicament dispensing device suitable for dispensing medicament from the open bag of a blister. It will be appreciated that the manifold may also be used for use with any suitable medicament dispensing device for dispensing medicine from an open bag.; wherein this bag can, for example, be provided by an open capsule of a capsule-shaped container. Thus, a medicament dispensing device for the delivery of powdered medicament is provided from an open bag of at least one package, the dispensing device (a) comprising a housing, (b) said housing comprising an air inlet; (c) enclosed in said housing, a dispensing mechanism for the dispensing of powdered medicament from an open bag of at least one package that can be received therein; and (d) associated with said dispensing mechanism and in communication with said air inlet, a manifold comprising: (i) a body, (ii) said body defining a chimney having a chimney inlet and a chimney outlet for directing the flow of air from said chimney inlet to said chimney outlet; (iii) further defining the body a chamber having a chamber inlet and a chamber outlet, (iv) wherein the chimney outlet and said chamber inlet rest side by side so that when said bag open of said container is positioned adjacent thereto, said air flow is directed from the chimney outlet to the chamber inlet by the open bag to draw said powdered medicament and allow the transport thereof in the air flow from the camera input to said camera output. where during the use of inhalation of the dispensing device by a patient, the air flow flows into the manifold chimney only through the air inlet arranged in the housing. Appropriately the medicament dispensing device of the invention is packaged inside a container (ie, an outer package, e.g. in the form of a complete wrapper) comprising a packing material that is intended to reduce the entry of ambient moisture into the dispenser (and its medicine package) packaged therein. The package is appropriately formed in any material that is impervious to or substantially impermeable to moisture. The packaging material is preferably permeable to volatile substances which can escape from the plastic forming the body of the inhaler and / or the medicine container in the form of an ampule, by diffusion or not, thereby preventing an increase in pressure. Other aspects and features of the invention are described in the appended claims and in the following detailed description of exemplary embodiments made with reference to the appended figures.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a perspective view of a medicament carrier in the form of a blister in the form of an elongated strip suitable for use with a medicament dispensing device according to the present invention; Figure 2 shows a sectional side view of a medicament dispensing device comprising the medicament carrier of Figure 1, the dispensing device being suitable for adaptation according to the present invention; Figure 3a shows a very schematic sectional side view of the base unit of a second drug dispensing device comprising a pair of medicament carriers of Figure 1 and suitable for use according to the present invention; Figure 3b shows a highly schematic perspective view of a detail of the base unit of Figure 3a; Figures 4a to 4c show in perspective view steps in sequence for preparing a third drug dispensing device for dispensing use by a patient; the device containing a pair of medicament carriers of Figure 1; Figures 5a to 5c show in side view corresponding to sequential steps for preparing the third drug dispensing device for use where the dispensing device is shown without a part of its outer housing; Figure 6 shows in exploded perspective view a gear mechanism of the third medicament dispensing device; Figures 7a to 7c show in side view details of the gear mechanism when it is ready for use in sequential steps corresponding to those of Figures 4a to 4c and 5a to 5c; Figure 8 shows in side perspective view a detail of a ratchet anti-return mechanism of the third medicament dispensing device; Figure 9 shows in side perspective view of the dispensing mechanism and the medicament carriers of the third medicament dispensing device; Figure 10 shows a partially exploded view of the third medication dispensing device, without its nozzle; Figure 1 1 shows a side view of a shell housing half of the third medicament dispensing device having a manifold disposed thereto; Figure 12 shows a sectional view of the third drug dispensing device; Figure 13 shows a sectional view of a nozzle assembly and a first manifold of the third medicament dispensing device; Figure 14a shows a side view of the first collector in Figure 13; Fig. 14b is a cross-sectional side view of the first collector taken on line XlVb in Fig. 15b showing its relation 'in use' with the medicament carriers of the third medicament dispensing device, Figs. 15a and 15b are views in cross-sectional plan of the first manifold taken in lines XVa and XVb in Figure 14a illustrating respectively the flow of primary air and purge therethrough during inhalation by a patient in the nozzle of the third medicament dispensing device; Figure 15c is a schematic cross-sectional side view of the first manifold taken on line XVc in Figure 14b showing the flow of primary and purge air therethrough during inhalation of a patient into the nozzle of the third dispensing device medicament; Figure 16a shows a side view of an alternative manifold suitable for use in the nozzle and cole assembly; ctor of Figure 13; Figure 16b is a cross-sectional side view of the alternative manifold taken on line XVIb of Figure 17b showing its 'in use' relationship with the medicament carriers of the third medicament dispensing device. Figure 17a shows a sectional view of the nozzle assembly and the alternative manifold of the third medicament dispensing device; and Figures 17b and 17c show cross-sectional plan views of the alternative manifold taken in lines XVII and XVIIc of Figure 16b illustrating respectively the flow of primary and purge air therethrough during inhalation of a patient. in the mouthpiece of the third medication dispensing device.

Detailed Description of the Drawings Figure 1 shows a medicament carrier 100 having the shape of an elongated blister strip. The medicament carrier 100, which is of the type used in the dry powder inhaler DISKUS® ADVAI R® of GlaxoSmithKIine Pie, comprises a flexible strip 102 defining a plurality of bags 104, each of which contains a dose (or part of it) of the inhalable powder medicine. The strip 102 is flexible enough to be rolled on a roller, as shown in Figure 1. The strip 102 comprises a base sheet 1 in which the ampoules 106 are formed, by cold forming or deep drawing, to define the bags 104 and a cover sheet 1 12 which is hermetically sealed to the base sheet 1 10, except in the region of the ampoules 106, to hermetically cover the bags 104. The hermetic sealing of the base and cover sheets 1 10, 1 12 is such that the base and cover sheets 1 10, 1 12 can be separated to open the bags 104 to access the powder medication. The sheets 1, 10, 12 are sealed to one another over their entire width except for the front end portions 14, 16 where they are not preferably sealed at all to each other. The cover sheets 1 12 and base 1 10 are each formed by a sheet of plastic / aluminum foil and are adhered to each other by heat sealing. The cover sheet 1 12 comprises, at least the following successive layers: (a) paper, adhesively bonded to (b) polyester; adhesively bonded to (c) aluminum foil, which is coated with at least one heat seal varnish to bond to the base sheet. The base sheet 1 10 comprises at least the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded to (c) a third layer comprising a polymeric material (e.g., polyvinyl chloride). Alternatively, the cover sheet 12 can be constructed as described in the international patent application No. PCT / US06 / 37438 filed on September 26, 2006. all the content of said international application and its application for the national phase of the The United States equivalent is incorporated herein by reference. The bags 104 are identical to each other and, with the exception of a test bag 108 at the front end of the strip 102, are spaced apart and equidistant along the length of the strip. The bags 104 are elongated and extend transversely to the length of the strip 102. This is convenient because it allows a large number of bags 104 to be disposed at a given strip length. The strip 102 may, for example, be provided with thirty, sixty or one hundred bags 104, but it is to be understood that the strip 102 may have any appropriate number of bags 104. Other details of the strip 102 may be found in the US patent. No. 5,590,645, the total content of which is incorporated herein by reference. In the embodiments of the present invention, examples of which come next, various strips 102 are employed in a single drug dispensing device, wherein each strip provides the constituent parts of a drug dose of a drug combination product. Each strip 102 can be of the same dimension and / or contain the same amount of dose (for example volume or mass) or in alternative embodiments, the strips of different dimensions and / or containing different amounts of doses can be used in combination.

Figure 2 shows a first portable and manual drug dispensing device in the form of a dry powder inhaler which can be adapted to comprise a manifold according to the present invention. The inhaler 220 is of the general type sold by GlaxoSmithKIine Foot under the trademark DISKUS®, the details of which are described in the patent of E. U. No. 5590,645 cited above, particularly with reference to figures 13 to 16 thereof. The inhaler 220 contains the medicament carrier of Figure 1 designated therein 202, the other characteristics of the strip being designated with the same assigned numbers. In more detail, the inhaler 220 is arranged to dispense unit doses of powdered medicament from the ampoule bags 204 of the elongated ampoule strip 202. The inhaler is constituted by an outer shell 221 containing the drug strip 202 within the body 222. The patient uses the inhaler by holding the device 220 in his mouth, squeezing the lever 224 and inhaling through the nozzle 226. The tightening of the the lever 224 activates the internal mechanism of the inhaler, so that the covering sheets 212 and base 210 of the wound medicament ampoule strip 202 are separated being removed with an index wheel 228, as a consequence of the pulling action of the lifting wheel of the cover sheet 230. It will be appreciated that once separated, the cover sheet 212 is wound around the lifting wheel. Figure 2 shows a first portable and manual drug dispensing device in the form of a powder inhaler. dry that can be adapted to comprise a manifold according to the present invention. The inhaler 220 is of the general type sold by GlaxoSmithKIine Foot under the trademark DISKUS®, the details of which are described in the above-mentioned U.S. Patent No. 5,590,645, particularly with reference to Figures 13 to 16 thereof. The inhaler 220 contains the medicament carrier of Figure 1 designated therein 202, the other characteristics of the strip being designated with the same assigned numbers. In more detail, the inhaler 220 is arranged to dispense unit doses of powdered medicament from the ampoule bags 204 of the elongated ampoule strip 202. The inhaler is constituted by an outer shell 221 containing the drug strip 202 within the body 222. The patient uses the inhaler by holding the device 220 in his mouth, squeezing the lever 224 and inhaling through the nozzle 226. The tightening of the the lever 224 activates the internal mechanism of the inhaler, so that the covering sheets 212 and base 210 of the wound medicament ampoule strip 202 are separated being removed with an index wheel 228, as a consequence of the pulling action of the lifting wheel of the cover sheet 230. It will be appreciated that once separated, the cover sheet 212 is wound around the lifting wheel 230. In turn, the separate base sheet 210 is wound around the lifting wheel of the base sheet 232. A unit dose of powdered medicament within the open blister pouch 204 'is released in the opening station 238 and can be inhaled by the patient to tr through the collector bag 240 and finally the nozzle 226. The exact shape of the manifold that will be provided to the collector bag 240 is not visible in FIG. 2, but will have a shape according to the present invention and is shown in the posterior figures Figures 3a and 3b are very schematic views of a second portable and manual drug dispensing device according to the present invention which is in the form of a dry powder inhaler and of the type described in US-A-2005/0154491 (Anderson ßt al), whose entire content is incorporated herein by reference. That is, the second medicament dispensing device is provided with two medicament carriers 300a, 300b in the form of the flexible ampoule strips 302a, 302b described above with reference to Figure 1 (identical reference numerals being used to designate the characteristics of the same). The flexible blister strips 302a, 302b are identical, the bags being in each of equal size and shape and being spaced and equidistant along the length of the strip. A first of the 302a strips contains the same powder medication in each of its bags, the amount of active ingredient (s) being the same in each bag of the strip. The other strip 302b also contains a powder drug if mil in each of its bags, each bag having again the same amount of active ingredient (s) in its interior. The powder medication in each strip may contain a single active ingredient or a mixture of active ingredients. However, the powder medication in a strip contains at least one active ingredient that is not in the other strip. As will be detailed below, in operation of the second medicament dispensing device, a bag of each ampoule strip 302a, 302b is peeled open to expose the different powdered medicaments therein. The patient then inhales into the nozzle to simultaneously inhale the powders of the open bags 304a, 304b of the strips 300a, 300b. The patient thus receives a fixed metered dose of powdered medicament from which the different powdered medicaments of each open bag 304a, 304b constitute the respective dose portions. Figure 3a illustrates a base unit 31 of the second medication dispensing device. The first and second ampoule strips 302a, 302b containing medicament are positioned within the respective chambers 323a, 323b, left and right of the base unit 31 9. Each ampoule strip 302a, 302b is attached to an index wheel of multiple respective bags 328a, 328b, and successive bags are thus guided to an opening station 333 commonly located. The rotation of the index wheels 328a, 328b is coupled. In the opening station 333, the metallic foil paper sheet portions 312a, 312b and base sheet 310a, 310b of each strip 302a, 302b are peeled around a respective peak 336a, 336b. The resulting empty base sheet 310a, 310b is wound into the respective base lifting chambers 332a, 332b. The used cover sheet 312a, 312b is directed to its respective peak 336a, 336b and wrapped around a cover lifting spindle 330a, 330b in the cover lifting chamber 331a, 331b. The powder-form medicament released from the open bags 304a, 304b of both the first strip 302a and the second strip 302b is accessible by a collector 350, which is only shown schematically in Figure 3b, but which in this embodiment adopts the form of one of the manifolds 450, 550 shown in Figure 14a or Figure 16a and described in detail with reference to the third medicament dispensing device of Figures 4 to 17. The collector 350 is located at the collector receiving station 341 In use, the released powder is displaced from the manifold 350 to a nozzle (not shown) in fluid communication therewith for its inhalation by the patient. The manifold 350 defines a particular geometry through which the freed powders are displaced to mix before being dispensed to the nozzle. The base unit 319 of Figure 3a allows different types of medication to be stored separately on each of the strips 302a, 302b but they are of simultaneous release and distribution thereof to the patient as a combined 'mixed' multi-active inhaled product. . Figure 3b shows the release of the drug from the open bags 304a, 304b (Figure 3a) in more detail. The patient inhales through the nozzle (not shown) resulting in a negative pressure transmitted through the manifold 350 to the ampoule bags 304a, 304b (FIG. 3a) of the strips 302a, 302b in the opening station 333. This Typically, it results in the creation of a venturi effect which causes the powder contained within each of the open bags 302a, 302b to be expelled through the manifold 350 and therefore to the nozzle for inhalation by the patient. Figures 4 to 15 provide various views of a portable and manual medicament dispensing device according to the present invention. The third drug dispensing device is in the form of a dry powder inhaler and, as will be understood by the qualified reader, is similar in terms of its function and its general principle of operation in the form of the second medication dispensing device mentioned above. That is, the third medicament dispensing device is provided with two medicament carriers 400a, 400b in the form of flexible ampoule strips 402a, 402b, as described above with reference to Figure 1, identical reference numerals being used to designate the characteristics of them. However, in the strips 402a, 402b the test bag is part of the equidistant spaced series of bags 404a, 404b, instead of being more spaced. The number of bags 404a, 404b in each strip 402a, 402b is the same, precise number depends on the days of treatment and the dosage regimen. By way of example, the strips 402a, 402b would have 31 bags for a 30 day treatment program once a day. The extra bag is the test bag. The flexible blister strips 402a, 402b are identical, the bags 404a, 404b being in each of the same shape and dimension and being spaced apart and equidistant along the length of the strip. A first of the strips 402a contains the same medicament powder in each of its bags, the amount of active ingredient (s) being the same in each bag of this strip. The other strip 402b also contains a powder medicine common in each of its bags, each bag having the same amount of active ingredient (s) therein again. The powder medication in each strip may contain a single active ingredient or a mixture of active ingredients. However, the powder medication in a strip contains at least one active ingredient that is not in the other strip. As will be detailed below, when the device has been prepared for use and a patient inhales from a mouthpiece 426 of the device, the patient simultaneously inhales the powder from a single open bag 404a, 404b from each strip 400a, 400b to receive a dose fixed measure of powdered medicament from which the different powdered medicaments of each open pouch constitute the respective dose portions. Figures 4a to 4c and Figures 5a to 5c each show corresponding sequential steps for preparing the third medicament dispensing device for use. As shown, the third medication dispensing device comprises a housing 420 provided with the nozzle 426 and a nozzle cover 438 for covering the nozzle 426. The housing 420 is also provided with a window 424 through which an indication is seen of the dose amount 425 of a dose counter (not shown). As will be described in more detail below, and as will be understood from Figures 6 and 9 to 15, the nozzle 426 interacts with a manifold 450 located in an aperture station 427, the manifold 450 being disposed, in use, for directing the powdered medicament from the single open bag of each strip 400a, 400b at the opening station 427 for inhalation by a patient. As can be seen in Figure 5a, the nozzle cap 438 has an arm 434 provided with an assembly opening 436 for interaction assembly as a ratchet 446 of a complex gear mechanism 40. In use, the nozzle cover 438 is it can rotate about an axis defined by the axis of rotation of the pawl 446. In Figures 4a and 5a, the nozzle cap 438 is in a first position in which the nozzle 426 is covered thereon. In Figures 4b and 5b, the nozzle cap 438 has been rotated to a second position, in which the nozzle 426 and the air intake grille 470 are partially uncovered but in which the gear mechanism 440 and a dispensing mechanism associated, described in more detail below, is not activated so that there is no dose of medication available for inhalation. Additionally, no action of the dose counter (not shown) has taken place whereby the quantity indicator 425 remains the same. The quantity indicator 425 in this particular mode indicates the number of unopened bags 404a, 404b remaining in each strip 402a, 402b. In Figures 4c and 5c, the nozzle cap 438 has been rotated again to a third position to fully discover or open the nozzle 426 and the air intake grille 470. Part of the lid 438 extends almost to the base 421 of accommodation 420 in this position. As a consequence of the subsequent movement from the second to the third position the gear mechanism (described in more detail with reference to Figures 6 and 7a to 7c below) and the dispensing mechanism (described in more detail with reference to Figure 9 more below) have been operated on the dispensing device to make a dose of medicament available for inhalation. In other words, the medication dispensing device is now primed for use. The movement has also resulted in the action of the dose counter (mechanism not visible) of the medication dispensing device so that the dose quantity indicator 425 is reduced in one unit in a new reading of '29'. After use, the nozzle cap 438 returns to the first position (ie, as in Figures 4a a and 5a). This corresponds to the storage position ('protected nozzle') of the dispensing device. Referring now to Figure 6, aspects of the gear mechanism 440 are shown. More in detail, it can be seen that the housing 420 is provided with a support frame 428 for external reception of the parts of the gear mechanism 440. Inside the chassis 428, and as best seen with reference to Fig. 9, there are dispensing mechanisms 448a, 448b arranged in mirror ("left" side and "right" side) to dispense medication. The gear mechanism 440 can be considered to be part of the gear mechanisms 448a, 448b. Referring to Figure 9, in more detail, the first and the second medicament containing blister strips 400a, 400b are positioned towards the left and right cameras, 403a, 403b, of the chassis 428. Each blister strip 400a, 400b it is coupled to the respective multi-bag index wheel 430a, 430b of the type used in the DISKUS® inhaler of GlaxoSmithKine, described and shown in US-A-2005/0126568 (Davies et al) -see figures 16, index wheel 416 - and in the "double strip" inhalation devices of US-A-2005/0154491 (Anderson et al), and the successive bags are therefore guided to a central opening station 427. In the opening station 427 , the cover sheet portions 412a, 412b and base sheet 410a, 410b of each strip 400a, 400b can be peeled off around the peaks 409a, 409b. The resulting empty base sheet 410a, 410b is wound into respective base lifting chambers 415a, 415b. The rotary base lifting spindle 413a, 413b anchors the end 414a, 414b of each respective base sheet 410a, 410b in its chamber 415a, 415b. The progressive rotation of each respective base lifting spindle 413a, 413b results in the 'waste' base sheet 410a, 410b which is wrapped around it in a tight coil. The rotation of each base spindle 413a, 413b is coupled to that of the respective index wheel 430a, 430b. The used cover sheet 412a, 412b is disposed over its respective peak 409a, 409b and wrapped around the cover lifting wheel 417a, 417b, which also rotates to wind the cover sheet 412a, 412b around it. Each cover lifting wheel 417a, 417b comprises a central hub, to which the ends 416a, 416b of the cover sheets 412a, 412b are fixed respectively and around which a central spindle (not shown) is wrapped around which it can rotate and on which a torsion spring (not visible) is mounted. This is described in detail in WO-A-2006/018261 (Glaxo Group Limited), in particular the modality described therein with reference to figures 1 to 4, whose international application, together with the United States patent application in the national phase derived therefrom, is incorporated herein by reference. The function of the torsion spring is to ensure that an approximately constant drive voltage is provided to each strip 400a, 400b by its cover lifting wheel 417a, 417b on the total length strip stroke. In particular, each torsion spring acts to compensate for variation in drive tension associated with the increase in effective winding diameter of each cover lift wheel 417a, 417b since the cover sheet 412a, 412b used is gradually wrapped around Of the same. In this way, the uniform indexing of each strip 400a, 400b can be maintained over the total length of the strip. In use, the dispensing device is primed as shown in Figures 4a to 4c and 5a to 5c by the movement of the lid 438 from the second position (as shown in Figures 4b and 5b) to the third position (as shown in Figures 4c and 5c) for operatingly rotating the index wheels 430a, 430b and the cover lifting wheels 417a, 417b to advance each blister strip 400a, 400b, thereby causing the front non-open bag of them be opened by peeling. To access the contents of the open bags, the patient then aspirates through the nozzle 426. As will be described in more detail with reference to figures 10 to 15, this results in a negative pressure that is transmitted through a manifold 450 to the open bag of each strip 400a, 400b in the opening station 427. This in turn results in the powder medicament contained within each of the open bags being simultaneously expelled through the common commutator 450 to the nozzle 426 and thus to the patient in the form of a dose of inhaled combination medicament. Referring again to Figure 6, it can be seen that the gear mechanism 440 comprises a ratchet gear 442 mounted on the control spindle 431. The ratchet gear 442, like the other gears, is a wheel shape having opposite faces and external faces 441, 443 (relative to the exterior of the dispensing device) and an outer circumferential surface 445a therebetween. The outer face 443 is concave to define an inner circumferential surface 445b in opposite relation to the outer circumferential surface 445a, as can be seen, the outer and inner circumferential surfaces 445a, 445b are provided with a stepped profile to provide respective characteristics 444a, 444b of external and inner ratchet for the ratchet interaction with ratchet 446, whose interaction will be described in more detail with reference to FIGS. 7a to 7c. The ratchet features 444a, 444b are equiangularly spaced ratchet teeth; in this embodiment there are 5 teeth on each circumferential surface 445a, 444b. The teeth 444a on the circumferential surface 445a (the 'outer teeth 444a') are offset from the teeth 444b on the inner circumferential surface 445b (the 'inner teeth 444b'). In other words, none of the inner teeth 444 rest on the same radius of the axis of rotation of the gear 442 as the outer teeth 444a. As will be seen in Figure 7a, the inner circumferential surface 445b comprises surface segments 449 that are each connected adjacent a pair of inner teeth 444b. Each surface segment 449 consists of first and second sections 449a, 449b extending inwardly from opposite ends of segment 449, with first section 449a extending inwardly toward second section 449b from an inner tooth 444b and extending the second section 449a. 449b inward toward the first section 449a from the next adjacent tooth 444b. The radius of curvature of the first section 449a is greater than the second section 449b whereby the second section 449b forms a ramp section with respect to the first section 449a. Referring to Figure 6, it will be appreciated that the base lifting spindles 41 3a, 413b and the spindles (not shown) of the cover lifting wheels 417a, 41 7b are respectively connected to the base lifting gears 462a, 462b and the cover lifting gears 461 a, 461 b. The index wheels 430a, 430b are also provided with gears. The internal face 441 of the ratchet gear 442 is provided with drive gear tooth 447 for driving the interaction (gear) with (i) the gear of a first index wheel 430a, and (ii) a first auxiliary gear. 464. The gear of the first index wheel 430a meshes with one of the cover lifting wheel gears 461 a and the gear of the second index wheel 430b, which in turn meshes with the second lifting gear of the index wheel 430b. coverage 461 b. The first auxiliary gear 464 meshes with a first of the base lifting spindle gears 462b and a second auxiliary gear 465, which in turn meshes with the second base lifting spindle gear 462a. This gear train arrangement provides indexing of the medicament carriers 400a, 400b and the winding on the base and cover plates 41 0a, b, 412a, b as the nozzle cap 438 moves from its second position to its third position. A more detailed description of a counter mechanism suitable for use in the dispensing device is provided in WO-A-2005/079727 (Glaxo Group Limited) which, together with the United States national phase patent application N °. 10 / 597,551 derived therefrom, will be incorporated herein by reference. The base lifting spindle 41 3b can be used to operate this counter mechanism by coupling with the drive wheel / lifting gear wheel thereof. As shown in Figures 6 to 8, the pack 446 comprises a central hub 446a from the outer circumference from which a plurality of circumferentially oriented, equiangularly spaced elastic legs 446b hang. The ratchet hub 446a further comprises a protrusion 446c which, as shown in Fig. 5a, fits into the mounting aperture 436 of the nozzle cover arm 434 to establish a direct drive connection between the nozzle cover 438 and ratchet 446 whereby the rotational movement of nozzle cover 438 between its first and third positions produces the rotational movement of ratchet 446 in the clutch gear 442, as will be described in more detail shortly later. In this particular embodiment, 5 ratchet legs 446b hang from the ratchet hub 446a. In other words, the number of cotter legs 446b is chosen to match the number of front teeth 444b of the lock gear 442. The interaction of the ratchet gear 442 with the ratchet 446 can be better understood with reference to the Figures 7a to 7c, showing a movement of the parts of the gear mechanism 440 of the third medicament dispensing device when it is ready to be used in sequential steps corresponding to those of Figures 4a to 4c. In this rest position of FIG. 7a (ie, the closed nozzle cap 438), the ratchet 446 is angularly disposed in the ratchet gear 442 so that the inner teeth 444b of the ratchet gear 442 are circumferentially spaced apart. of the free ends of the ratchet legs446b. In the second position of Figure 7b (i.e. nozzle cover 438 partially open), pawl 446 has rotated about ratchet gear 442 to slide pawl legs 446b onto adjacent surface segments 449 of the circumferential surface inner 445b for engaging the inner teeth 444b. It will be appreciated therefore that in this second position, the ratchet gear 442 is ready to move but still does not move, and therefore the total gear mechanism 440 and the dispensing mechanisms 448a, 448b do not advance. In the third position of Figure 7c, (ie, the nozzle cap 438 fully open), both the pawl 446 and the pawl gear 442 rotate together (about 72 ° as shown) through the inter-coupling of the paws of gear 446b and inner teeth 444b to advance the total gear mechanism 440 and dispensing mechanisms 448a, 448b to thereby index or advance each medicament carrier 400a, 400b to open a solitary bag of each and make available therefore the powder medicament contained in each bag opened in the manifold 450 in the opening station 427 for the simultaneous inhalation of the patient through the open nozzle 426. Referring to FIG. 8, the dispensing device further comprises an internal retaining plate 481 for covering the gear mechanism 440. The retaining plate 481 is provided with an arcuate sleeper 483 that rests on the driving gear. inlet 442 and pawl 446. One end of sleeper 483 is configured as an elastic finger 484 in which a notch 485 is disposed. Ratchet 446 includes a protrusion 446d which engages in the notch when the pawl (and therefore the pawl nozzle cap 438) is in the first rest position of figure 7a, as shown in figure 8. This inter-coupling of the ratchet protrusion 446d and the notch of the retainer plate 485 acts as a stopper to stop the cover nozzle 438 in the 'closed mouth' or rest position of Figures 4a, 5a, 7a and 8. The retainer plate 481 further comprises a fixed spring detent leg 487 for interacting with the outer teeth 444a of the gear of ratchet 442 to form a 'non-return' feature for the ratchet gear 442. When the nozzle cover 438 is open, to produce the rotation of the pawl 446 and then the tri-gear nip 442 once the ratchet legs 446b mesh with the inner teeth 444b, the fixator leg 487 passes over the outer teeth 444a due to its orientation and the elasticity of the sear leg 487. However, when the cap nozzle 438 is returned to its closed position, in turn turning ratchet 446 back to its rest position, ratchet gear 442 is held against reciprocating return by engagement of sear leg 487 with one of the outer teeth 444a. Accordingly, the reverse rotation of the pawl 446 upon closing the nozzle cap 438 is not transmitted to the gear mechanism 440. In this way, on each occasion the nozzle cover 438 opens and closes completely. The ratchet gear 442 is increased in a rotary direction only. When the nozzle cap 438 is returned to its first covering position (FIG. 4a), to rotate the pawl 446 in the ratchet gear 442 back to its rest position (FIG. 7a) the elastic legs 446b are again slid over. the inner circumferential surface 445b to be spaced behind the different inner teeth 444b ready for the next opening of the nozzle cover 438. An enlarged view of one of the gear teeth of the index wheel 430a is shown in Figure 7a. showing the profile of it. The gear teeth of all the gears in the gear mechanism are provided with this profile. In summary, the manual movement, by the patient, of the nozzle cap 438 of its first position, in which it closes the nozzle 426 (for example figure 4a), to its third position, in which the nozzle is fully opened 426 (e.g., Figure 4c) results in the ratchet 446 driving the drive and control mechanisms 440, 448a, 448b so that each blister strip 402a, 402b is indexed in the dispensing device to make a single bag of ampoule 404a, 404b of each strip 402a, 402b is opened and present in the manifold 450 at the opening station 427 ready for the patient to simultaneously inhale the powder content of each newly opened bag 404a, 404b and thereby receive a fixed dose of a combination of different active drugs. After the patient has inhaled the powder content of each newly opened pouch, the patient manually returns the nozzle cap 438 to its first position ready for its next use. In the next use, the next closed bag 404a, 404b on each strip 402a, 402b will be opened and indexed to the manifold 450 to allow the patient to inhale the next fixed dose of the drug combination. This cycle of opening and closing then continues according to the prescribed regimen for the drug combination (for example once a day, twice a day, etc.) until all the bags 404a, 404b are empty, as can be evidenced by the quantity indicator 425. As described above, the movement of the nozzle cap 438 from its first position to the second intermediate position (e.g. Figure 4b) does not result in the indexing / opening of the blister bags 404a, 404b. A more detailed description of the manifold 450 of the third medicament dispensing device now follows with reference to Figs. 10 to 15. Fig. 10 shows the third medicament dispensing device without its nozzle 426. In more detail, the housing 420 comprises coupling the first 420a and the second 420b shell lid part, which in combination act to house the mechanism of the dispensing device thereof. The manifold 450 is received by the first shell lid part 420a so that a covering defining an inlet 453 to a chimney 452 is received within an inner wall 472 of the first shell lid part 420a which defines the grate 454. air inlet 470. As described above, and as shown in Figures 4a to 4c, the air inlet grate 470 in the first shell cap part 420a is covered by the nozzle cap 438 in its first position or closed position (figure 4a), partially uncovered when the nozzle cap 438 is in its second or partially open position (figure 4b) and fully uncovered when the nozzle cover 438 is in its third or open position (figure 4c) .

In use, the air inlet grate 470 allows the air to pass from the outside of the third medicament dispensing device to the manifold 450 by the entrance of the chime 453 to the chime 452 in response to the inhalation of the patient through of the nozzle 426, as schematically indicated by arrow 483 in FIG. 12. Notably, this air inlet grille 470 provides the single point of intended entry of air from outside to the medication dispensing device when inhalation occurs. of the patient in the nozzle 426. More particularly, the air inlet grating 470 provides the single point of air entry on the outside of the dispensing device to pass to the manifold 450 upon patient inhalation in the nozzle 426. manifold 450 is also received by a second shell cover portion 420b so that its protruding foot 455 sits towards the rec bag collector 475 thereof. The manifold 450 is provided with a pair of wings 456a, 456b which are mounting features that allow the manifold 450 to be pushed over the nozzle 426. As can also be seen by reference to FIGS. 1 2 a 1 5, the manifold 450 has a particular interior structure in which the chi chime 452 is located above a chamber 460 and partially shares a common wall 459, said common wall 459 forms the lower wall of the chime 452 and a part of the upper wall of the chamber 460. The terms "above", "lower" and "upper" are used only to describe the relative positioning of the features in the manifold 450 in the orientation that the manifold 450 is shown in the Figures 12 and 13. The chimney 452 has the chimney inlet 453 and a pair of chimney outlets 454a, 454b. In use the chimney 452 directs inward the air flow (as exclusively received through the air inlet grille 470 upon inhalation of the patient in the nozzle 426) from the chimney inlet 453 to the exhaust outlet pair. chimney 454a, 454b. The camera 460 has a pair of camera inputs 473a, 473b and a camera output 474. The pair of chimney outputs 454a, 454b and the pair of camera inputs 473a, 473b are both defined by a pair of circular holes, in this particular mode of diameter of about 3 mm, and each hole is provided with a respective cruciform element 451, 461. Each chimney outlet 454a, 454b is matched to one of the chamber inlets 473a, 473b by positioning them adjacent to one another. The nozzle 426 is disposed at the chamber outlet 474 and is press-fitted thereto by a press-fit feature 476. As detailed above, when the nozzle cover 438 is fully open in its third position, the mechanisms of gears and dispensing 440, 448a, 448b are actuated to make each blister strip 400a, 400b advance and a single bag 404a, 404b of each strip to be peeled open. As will be understood from Figs. 14b and 15c, the peeled open blister pouch 404a, 404b of each strip 400a, 400b rests adjacent to a respective pair of chimney outlet pairs 454a, 454b and chamber inlets 473a 473b. Specifically, the open blister pouch 404a of the first blister strip 402a is located adjacent to the first chimney outlet 454a and the first chamber inlet 473a (as shown in Figure 15c) and the open blister pouch 404b of the second blister strip 402b is equally adjacent to the other chimney outlet 454b and the other chamber inlet 473b. As described above with reference to Figure 1, the blister bags 404a, 404b are elongated, extending laterally with respect to the longitudinal axis of the strip 402a, 402b. The bags 404a, 404b can therefore be considered as having a first and a second side on opposite sides of the longitudinal axis of the strip. When the bags open 404a404b are presented to the manifold 450 in the opening station 427, the bags 404a, 404b are oriented so that their lateral orientation is aligned with the direction between the respective flue outlets 454a, b and the chamber inlets 473a, b. In this way, as shown in Figure 15c, the chimney outlets 454a, b and the chamber outlets 473a, 473b rest on different sides of the bags 404a, 404b, whereby, in use, the air flows through the bags 404a, 404b in their lateral orientation, ie lateral with respect to the longitudinal axis (or longitudinal direction) of the strip 402a, 402b. As shown in FIGS. 12, 13 and 15, when a patient inhales in the nozzle 426, an air stream 483 flows from the outside of the dispensing device to the manifold 450 only through the air intake grille. 470 towards the chimney 452 by the chimney inlet 453, which is in juxtaposition relationship with respect to the air intake grille 470. As graphically depicted in Figures 1 3, 1 5a and 1 5c, the first portions 485 ( or primary) of this stream of air 483 flow to the open blister pouch 404a, 404b of each strip 400a, 400b in the opening station 427 by the respective chimney outlets 454a, 454b, thereby pulling the medicament into powder contained in the bags in the air stream, and therefore outside the bags 404a, 404b towards the chamber 460 by the chamber inlets 473a, 473b. The air stream with entrained powdered medicament then flows out of the nozzle 426 into the patient's respiratory system. As shown in Figures 12 to 15, a single D-shaped vent hole 480 is provided in the wall 459 that separates the chimney 452 from the chamber 460. The D 480 vent hole is located adjacent to both to the chimney outlets 454a, 454b as the chamber inlets 473a, 473b. As depicted graphically in Figures 13, 15b, and 1 5c, in use, the purge hole 480 acts in such a manner as to direct a second portion 486 of the air stream 483 (the "purge portion") from the chimney 5452 directly into chamber 460 to impact disruptively with first portions 485 of air stream 483 that transport the entrained powdered medicament into chamber 460 and thereby disintegrate any agglomerated powder component thereof. It should be noted that figures 15a and 15b only selectively show the flow paths of first 485 and second 486 portion of air stream 483 for reasons of ease of illustration. As will be appreciated by the person skilled in the art, the first and second portions 485, 486 are created concurrently in the manifold 450 upon inhalation of the patient in the nozzle 426, as indicated in FIGS. 13 and 15c. Figures 16 and 17 show a second manifold 550 for the third medicament dispensing device which is a variation of (and alternative to) the manifold 450 with a hole hole in the 'D' shape. The characteristics of the second collector 550 corresponding to characteristics of the first collector 450 are designated with identical reference numerals. It will be appreciated that the overall shape and shape of this second manifold 550 corresponds to that of the manifold 450 of the D-shaped hole so that it can easily be replaced by the other in the third medicament dispensing device. However, instead of the "D-shaped hole" type vent hole 480, the second manifold 550 has two elongated slot-shaped purge holes 580a, 580b disposed on the wall 559, which separates the chimney 552 from the chamber 560. In more detail, second collector 550 has an internal structure in which chimney 552 is located above chamber 560 and partially shares a wall 559 therewith, said wall 559 forming the lower wall of chimney 552 and a part of the upper wall of chamber 560. The terms "above", "lower" and "upper" are used only to describe the relative positioning of the features in the collector 550 in the orientation that the collector 550 is shown in FIGS. 17a. The wings 556a, 556b are arranged in the collector as before. The chimney 552 has a chimney inlet 553 and a pair of outlets 554a, 554b. In use, the chimney 552 directs inward the air flow 583 (again, as exclusively received through the air inlet grate 470 as shown in Figure 17a) from the chimney inlet 553 to the outlets 554a, 554b. Chamber 560 has a pair of chamber inlets 573a, 573b and a chamber outlet 574. Chimney outlets 554a, 554b and chamber inlets 573a, 573b are both defined by circular holes of diameter of approximately 3 mm, and each The hole is provided with a respective cruciform feature 551, 561. As shown in Figures 17a and 17b, the chimney outlets 554a, 554b and the chamber inlets 573a, 573b are positioned to be adjacent to one another such that when an open blister pouch 404a, 404b (see Figs. 16b and 17a) rest adjacent thereto in an opening station 427 (eg Fig. 11), the first portions 585 of the internal air flow 583 are directed by the open bags 404a, 404b from the chimney outlets 554a, 554b to the chamber inlets 573a, 573b and to the chamber 560. This air flow in the open blister bags 404a, 404b draws the powder content of the respective bags 404a, 404b and allows their transport in the airflow of inhalation 583 from chamber inlets 573a, 573b to chamber outlet 564, and thus inhaler patient through nozzle 426. Bleed holes 580a, 580b in elongated slot form are disposed on wall 559 that separate to the chimney 552 of the chamber 560. The purge holes 590a, 580b in the form of an elongated slot are located remote from both the chimney outlets 554a, 554b and the chamber inlets 573a, 5473b. As graphically depicted in Figures 13a and 17c, in use, the purge holes 580a, 580b act in such a manner as to direct a second portion 586 of the air stream 583 (the "purge portion") from the chimney 552 directly into the chamber 560 to impact disruptively with the first portions 585 of the air flow 583 that transport the entrained powdered medicament into the chamber 460 and thereby disintegrate any agglomerated powder component therefrom. Referring to Figures 16a, each purge hole 580a, 580b has a width at its first end closest to the chamber exit 574 of 1.32 mm (± 0.15mm), a width at the second opposite end opposite at the chimney exit 554a, 554b of 1.1 1 mm (± 0.15mm), and a length from the first end to the second end of 6.465mm (± 0.1 mm). The cross-sectional area of each purge hole 580a, 580b is 7.8mm2. The purge holes 580a, 580b therefore have a conical profile, which tapers from the first end to the second end. Of course, these dimensions may change depending on the drugs to be delivered from the strips 402a, 402b. As will be appreciated, the first and second portions 585, 586 of the air stream 583 are produced concurrently in the manifold 550 as a result of inhaling the patient in the nozzle 426. As will also be seen from FIG. 17c, the Bleeding holes 580a, 580b are configured such that the second portions 586 of the air stream 583 further flow around the boundary surface 591 of the chamber 560, forming a sheath-like air layer adjacent the boundary surface 591. This helps to alleviate the deposition of the powdered medicament on the boundary surface 591 when the powder is brought to the nozzle 426. It will be noted that the internal structure of the manifolds 450, 550 is such that the longitudinal axis of the chimney 452, 552 extending from the chimney inlet 453, 553 to the partition wall 459, 559, is perpendicular or generally perpendicular to the longitudinal axis of the chamber 460, 560, which is extends from the camera inputs 473a, b; 573a, b at the exit of chamber 474; 574. In this way, the purge portions 486; 586 of the inhalation stream 483; 583 impact first, against the 485 portions; 585 who carry medication in chamber 460; 560 forming right angles to it or generally at right angles to it. It will also be noted that the collectors 450; 550 require that all air flow inside the manifold be by the chimney inlet 453; 553, which then acts to 'separate' this total air flow 483; 583 in the air portion 485; 585 'directed open bag' (by the chimney outlets 454a, b; 554a, b and the chamber inlets 473a, b; 573a, b) and a portion of air 486; 586 of 'purge' (by one or more purge holes 480; 580a, b) to chamber 460; 560. Good control over the amount of purge air 486; 586 and, in particular, the percentage thereof (with respect to the total air flow entering the manifold 450, 550 through the chimney inlet 453; 553) is then possible with a manifold having this arrangement. For the third medicament dispensing device, having a pair of medicament carriers 400a, 400b, the purge air portion 486; 586 of the air flow 483; 583 total is ideally 80%, or substantially 80%, with the remainder passing through the open bags 404a, 404b. It will be appreciated that there is probably some air leakage within the manifolds 450; 550 upon inhalation of the patient in the nozzle 426, particularly by the chimney outlets 454a, b; 554a, b and perhaps more particularly by the chimney entries 473a, b; 573a, b, since the blister strips 402a, 402b do not form a complete sealing fit over the openings towards the manifold 450; 550. However, any air leak is negligible compared to the inhalation air flow 483; 583 expected total that flows into the collector 450; 550 through the chimney entrance 453; 553 by the air inlet grate 470. In the above-described embodiments, the manifolds 450; 550 are plastic components molded by injection in one piece. More particularly, the collectors 450; 550 are made from high density polyethylene (HDPE), since this material is suitable for the injection molding of collector 450; 550, in particular high-speed injection molding, although it has a sufficiently high surface energy to minimize or inhibit the deposition of powdered medicament thereon. However, other materials and manufacturing or molding process can be used. Other possible materials include fluoropolymers, for example fluorinated ethylene-propylene (FEP), and other non-fluoropolymers, for example polypropylene (PP). It can be appreciated that any of the parts of the device or any component thereof that comes into contact with the medicament can be constituted of or coated with material such as fluoropolymer materials (e.g. PTFE or FEP) that reduce the tendency of the medicament to adhere to the same. Any moving parts may also have coatings applied thereto that improve their desired movement characteristics. The friction coatings can therefore be applied to improve the friction contact and the lubricants (for example silicone oil) used to reduce the friction contact when necessary. In particular, the collector itself can be totally or partially constituted of or alternatively partially or totally coated with materials that reduce the tendency of the medicament to adhere to it. Such materials may, for example, reduce the surface energy of the relevant surface of the collector Appropriately, the fluoropolymer materials are used High-density polyethylene (HDPE) and / or modified acetal materials are also suitable.

Suitable fluoropolymer materials include those comprising multiples of one or more of the following monomer units: tetrafluoroethylene (PTFE), fluorinated ethylene-propylene (FEP), perfluoroalkoxyalkane (PFA), ethylenetetrafluoroethylene (ETFE), vinylfluorofluoride (PVDF), and chlorinated ethylenetetrafluoroethylene. Fluorinated polymers having a relatively high ratio of fluorine to carbon, such as perfluorocarbon polymers, for example PTFE, PFA and FEP are particularly suitable. Particularly when used as a coating, the fluoropolymer is optionally mixed with a non-fluorinated polymer such as polyamides, polyimides, polyamideimides, polyethersulfones, polyphenylene sulfides, and thermosetting amino-formaldehyde resins. These aggregate polymers often improve the adhesion of the polymer coating to the substrate. Preferred polymer blends are PTFE / FEP / polyamideimide, PTFE / polyether sulfone (PES) and FEP-benzoguanamine. It will also be appreciated that the 'Summary of the invention' section describes additional details, modifications or adaptations for the exemplary drug dispensing devices, medicament carrier (s) and manifolds described with reference to the accompanying figures. Where they are not indicated, the components of the medicament dispensing devices of the present invention may be made from conventional engineering materials, especially conventional plastics engineering materials, more especially those that allow the molding of the component. The medicament dispensing device of the present invention is for dispensing powdered medicament formulations, particularly for the treatment of respiratory disorders such as asthma and chronic obstructive pulmonary disease (EPCOC), bronchitis and chest infection. In particular, the device can be used in the distribution of a drug powder formulation based on one or more of the drugs listed below. Where the collector is to be used with only one package, the medicament formulation in that blister may comprise only one of the listed drugs (a monotherapy) or a plurality of the listed drugs (combination therapy). When the device is to be used with various blister packs (in particular two), each package may contain a powdered medicament formulation comprising one or more of the listed medicaments, containing at least one medicament package not found therein. or at least one of other containers. When the device is for use with two blisters, the formulation of powdered medicament in a package comprises a medicament that is not found in the other package. Typically, each container will have different medications from those of the other container. The appropriate medicaments can thus be selected from, for example, analgesics, for example codeine, dihydromorphine, ergotamine, fentanyl or morphine, anginal preparations, for example diltiazem; antiallergics, for example cromoglycate (for example in the form of a sodium salt) quetotifen or nedocromil (for example sodium salt), antiinfectants for example cephalosporins, penicillins, streptomycin, sulfonamides, tetracyclines and pentamidine; antihistamines, for example metapyrylene; anti-inflammatories, for example beclomethasone (for example the dipropionate ester), fluticasone (for example, the propioonate ester), flunisolide, budesonide, rofleponide, mometasone, for example in the form of fluorate ester), ciclesonide, triamcinilone (for example, acetonide), or S- (2-oxo-tetrahydrofuran-3-yl) ester of 6a, 9 a-difluoro-1 I -hydroxy-1-methyl-S-oxo- ^ a-propionyloxyandrosta-l ^ -dieno- ^ ß-carbothioic; antitussives, for example noscapine; bronchodilators, for example albuterol (for example as a free base or sulfate), salmerterol (for example xinafoate) ephedrine, adrenaline, fenoterol (for example as hydrobromide), salmefamol, carbuterol, mabuterol, entanterol, naminterol, clenbuterol, flerbuterol, bambuterol, indacaterol, formoterol (for example fumarate), isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pibuterol (for example as acetate), reproterol, (for example as hydrochloride), rimiterol, terbutaline (for example as sulphate), isoetarin, tulobuterol or 4-hydroxy-7- [2- [2 [2 - [[3- (2-phenyl-ethoxy) propyl) ] sulfonyl] ethyl] amino] ethyl] -2 (3H) -benzothiazolone; adenosine agonists 2a, for example 2R, 3R, 4S, 5R) -2- [6-amino-2- (1S-hydroxymethyl-2-phenyl-ethyl-amino) -purin-9-yl] -5- (2- eti 1-2 H-tetrazol-5-yl) -tetrahydrofuran-3,4-diol (for example as maleate); Integrin inhibitors for example, (2S) -3- [4- ( { [4- (aminocarbonyl) -1-piperidinyl] carbonyl} oxy) phenyl] -2 - [((2S) -4- methyl-2- { [2- (2-methylphenoxy) acetyl] amino.}. pentanoyl) amino] propanic (for example as free acid or potassium salt), diuretics, for example, amiloride; anticholinergics, for example. , ipratropium (for example, as bromide), tiotropium, atropine or oxitropium; hormones, for example, cortisone, hydrocortisone or prednisolone; xanthines, for example, aminophylline, theophyllinate choline, theophylline or theophylline lysine; therapeutic proteins and peptide, for example, insulin or glucagon; vaccines, diagnostic agents, and gene therapy. It is evident that for the person skilled in the art, when appropriate, the medicaments can be used in the form of salts, (for example, as alkali metal or amine salts or as acid addition salts) or as esters (for example, lower alkyl esters) or as solvates (e.g., hydrates) to optimize the activity and / or stability of the medicament. The formulated pharmacological product may in some aspects be a monotherapy product (i.e. containing a single active drug) or it may be a combination therapy product (ie containing various active medicaments). The drugs or appropriate pharmacological components of a combination therapy product are typically selected from the group consisting of anti-inflammatory agents (eg, a corticosteroid or an NSAI D), anticholinergic agents (eg, an M 2 M 2 receptor antagonist, M ^ M? Or M3), other ß2 adrenoreceptor agonists, anti-infective agents (for example, an antibiotic or an antiviral), and antihistamines. All combinations can be considered. Anti-inflammatory agents include corticosteroids and NSAIs Ds. Suitable corticosteroids that can be used in combination with the compounds of the invention are oral and inhaled corticosteroids and their prodrugs having anti-inflammatory activity. Examples include methyl prednisolone, prednisolone, dexamethasone, fluticasone propionate, S-fluoromethyl ester of 6a, 9a-difluoro-17a - [(2-furanylcarbonyl) oxy] -1 1ß-hydroxy-16-methyl ethyl-3- oxo-androsta- 1, 4-diene-17β-carbothioic acid, S- (2-oxo-tetrahydro-furan-3S-yl) ester of 6a, 9a-difluoro-1 1 -hydroxy-16a-methyl- 3-oxo-17a-propionyloxy-androsta-1,4-diene-17β-carbothioic acid, beclomethasone esters (eg 17-propionate ester or 17,21-dipropionate ester), budesonide esters, flunisolide, mometasone (eg, the furoate ester), triamcinolone acetonide, rofnide, ciclesonide, butixocort propionate, RPR-106541, and ST-126. Preferred corticosteroids include fluticasone propionate, S-fluoromethyl ester of 6a, 9a-difluoro-1β-hydroxy-16a-methyl-17a - [(4-methyl-1,3-thiazole-5-carbonyl) oxy] -3-oxo-androsta-1, 4-diene-17β-carbothioic acid, S-fluoromethyl ester of 6a, 9a-difluoro-17a - [(2-furaniylcarbonyl) oxy] -1 1 ß-hydroxy-16a-methyl -3-oxo-androsta-1, 4-diene-17β-carbothioic acid, S-cyanomethyl ester of 6a, 9a-difluoro-1 1β-hydroxy-16a-methyl-17a- (2,2,3,3 -tetra-mycyclopropylcarbonyl) oxy-3-oxo-androsta-1,4-diene-17β-carbothioic acid, S-fluoromethyl ester of 6a, 9a-difluoro-1β-hydroxy-16a-methyl-17a- (1-mymethocyclopropylcarbonyl) ) oxy-3-oxo-androsta-1,4-diene-17β-carbothioic acid and 9a, 21 dichloro-1β, 17a methyl-1,4, pregnadiene, 3, 20 dione-17- [2 '] furoate (mometasone furoate) ). Other corticosteroids are described in WO02 / 088167, WO02 / 100879, WO02 / 12265, WO02 / 12266, WO05 / 005451, WO05 / 005452, WO06 / 072599 and WO06 / 072600. Non-asteroid compounds having glucocorticoid agonism that can process the selectivity for transrepression upon transactivation and which may be useful in combination therapy through the collector of the present invention are described in WO03 / 082827, WO98 / 54159, WO04 / 005229, WO04 / 009017, WO04 / 018429, WO03 / 104195, WO03 / 082787, WO03 / 082280, WO03 / 059899, WO03 / 101932, WO02 / 02565, WO01 / 16128, WO00 / 66590, WO03 / 086294, WO04 / 026248, WO03 / 061651, WO03 / 08277, WO06 / 000401, WO06 / 000398 and WO06 / 015870. Suitable NSAIs include sodium cromoglycate, nedocromil sodium, phosphodiesterase (PDE) inhibitors (eg, theophylline, PDE4 inhibitors or mixed PDE3 / PDE4 inhibitors), leukotriene antagonists, leukotriene synthesis inhibitors, NOS inhibitors , tryptase and elastase inhibitors, beta-2 integrin antagonists and adenosine receptor agonists or antagonists (eg, adenosine agonists 2a), cytokine antagonists (eg, chemokine antagonists), inhibitors of cytokine synthesis or inhibitors of 5-lipoxygenase. Examples of NOS inhibitors include those described in WO93 / 13055, WO98 / 30537, WO02 / 50021, WO95 / 34534 and WO99 / 62875. Examples of CCR3 inhibitors include those described in WO02 / 26722. Bronchodilators are β2-adrenoreceptor agonists, including salmeterol (which may be a racemate or a simple enantiomer, such as the R-enantiomer), for example salmeterol xinafoate, salbutamol (which may be a racemate or a simple enantiomer such as? -enantiomer), for example salbutamol sulfate or as the free base, formoterol (which may be a racemate or a single diastereomer, such as R, R-diastereomer), for example formoterol fumarate or terbutaline or salts thereof. Other suitable agonists of the β2 adrenoreceptors are 3- (4- {[[6- ( { (2R) -2-hydroxy-2- [4-hydroxy-3- (hydroxymethyl) phenyl] ethyl} amino. ) hexyl] oxy!} butyl) benzenesulfonamido, 3- (3. {[[((({{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{{2}}}}}} ethyl} } -amino) heptyl] oxy} propyl) benzenesulfonamido, 4-. { (1 R) -2 - [(6- { 2- [(2,6-dichlorobenzyl) oxy] ethoxy} hexyl) amino] -1-hydroxyethyl} -2- (hydroxymethyl) phenol, 4-. { (1 R) -2 - [(6- { 4- [3- (Cyclopentylsulfonyl) phenyl] butoxy}. Hexyl) amino] -1-hydroxyethyl} -2- (hydroxymethyl) phenol, N- [2-hydroxyl-5 - [(1 R) -1-hydroxy-2 - [[2-4 - [[(2R) -2-hydroxy-2-phenylethyl] amino ] phenyl] ethyl] amino] ethyl] phenyl] formamido, and N-2. { 2- [4- (3-phenyl-4-methoxyphenyl) aminophenyl] ethyl} -2-hydroxy-2- (8-hydroxy-2 (1 H) -quinolinon-5-yl) ethylamine, and 5 - [(/?) - 2- (2-. {4- [4- (2 -amino-2-methyl-propoxy) -phenylamino] -phenyl.}. -ethylamino) -1-hydroxy-ethyl] -8-hydroxy-1 H -quinolin-2-one. Preferably the β2 adrenoceptor agonist is a long-acting β2-adrenoceptor agonist (LABA), for example a compound that provides effective bronchodilation for 12 hours or more. Other ß2 adrenoreceptor agonists include those described in WO 02/066422, WO 02/070490, WO 02/076933, WO 03/024439, WO 03/072539, WO 03/091204, WO 04/016578, WO 2004/022547. , WO 2004/037807, WO 2004/037773, WO 2004/037768, WO 2004/039762, WO 2004/039766, WO01 / 42193 and WO03 / 042160. Inhibitors of phosphodiesterase 4 (PDE4) include compounds that are known to inhibit the PDE4 enzyme or that have been found to act as a PDE4 inhibitor, and which are only PDE4 inhibitors, not compounds that inhibit other members of the PDE family as well as PDE4. It is generally preferred to use a PDE4 inhibitor having an IC50 ratio of about 0.1 or higher relative to IC50 for the catalytic form of PDE4 that binds rolipram with a high affinity divided by the IC50 for the form that binds to rolipram with a low affinity. For the purposes of this disclosure, the catalytic site of AM Pc that binds R and S rolipram with a low affinity is termed the "low affinity" binding site (LPDE 4) and the other form of this catalytic site that is binds rolipram with a high affinity is called the "high affinity" binding site (HPDE 4). This term "HPDE4" should not be confused with the term "hPDE4" which is used to mean human PDE4. A method for determining IC50 ratio is set forth in U.S. Patent No. 5,998,428 which is incorporated herein by reference in its entirety. See also PCT application of WO 00/51599 for another description of this test. Suitable inhibitors of PDE4 include compounds that have a therapeutic health relationship, ie, compounds that preferably inhibit the catalytic activity AM Pc where the enzyme is in the form of binding to rolipram with a low affinity, thereby reducing the side effects that are apparently linked to the inhibition of the form that binds to rolipram with a high affinity. Another manner of exposure is that in which preferred compounds will have an IC5o ratio of about 0.1 or more relative to IC5o for the catalytic form PDE4 that binds rolipram with a high affinity divided by IC50 for the form that joins the rolipram with low affinity. Another refinement of this standard is that the PDE4 inhibitor has an IC50 ratio of about 0.1 or more, such ratio is the ratio of the IC50 value to compete with the binding of 1 nM of [3H] R-rolipram to a form of PDE4 that binds rolipram with high affinity on the IC50 value to inhibit the PDE4 catalytic activity in a way that binds rolipram with a low affinity using 1 μM [3 H] -AM Pc as the substrate. Most PDE4 inhibitors have an IC50 ratio of greater than 0.5, and particularly those compounds that have a ratio greater than 1.0. Preferred compounds are cis-4-cyano-4- (3-cyclopentyloxy-4-methoxyphenyl) -cyclohexane-1-carboxylic acid, 2-carbomethoxy-4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexane-1 - ona and c / 's- [4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-ol]; these are examples of compounds that preferably bind to the low affinity binding site and have an IC50 ratio of 0.1 or more. Other suitable pharmacological compounds include, c / s-4-ci and ano-4- [3- (cyclopentyloxy) -4-methoxy-1-ene] cyclohexane-1-carboxylic acid (also known as "cilomalast") described in US Patent 5,552,438 and its salts, esters, prodrugs or physical forms; AWD-12-281 elbion (Hofgen, N. et al 15th EFMC I nt Symp Med Chem (Sept 6-10, Edinburgh) 1998, Abst P.98, CAS reference No. 247584020-9); a 9-benzyl adenine derivative called NCS-613 (INSERM); D-4418 of Chiroscience and Schering-Plow; a benzodiazepine PDE4 inhibitor identified as CI-1018 (PD-168787) and attributed to Pfizer; a benzodioxole derivative described by Kyowa Hakko in WO99 / 16766; K-34 of Kyowa Hakko; V-1 1294A by Napp (Landells, L.J. et al., Eur Resp J [Annu Cong Eur Resp Soc (Sept 19-23, Geneva) 1998] 1998, 12 (Suppl 28): Abst P2393); roflumilast (reference CAS No 162401 -32-3) and a phthalazinone (WO99 / 47505, the disclosure of which is incorporated by reference) by Byk-Gulden; Pumafentrine, (-) - p - [(4aR *, 10¿> S *) - 9-ethoxy-1, 2,3,4,4a, 10b-hexahydro-8-methoxy-2-methylbenzo [c] [1, 6] nafthiridin-6-yl] -N, N-diisopropylbenzamide which is a mixed inhibitor of PDE3 / PDE4 which has been prepared and published by Byk-Gulden, now Altana; arophylline under development by Almirall-Prodesfarma; VM554 / UM565 from Vernalis; or T-440 (Tanabe Seiyaku, Fuji, K. et al., J Pharmacol Exp Ther, 1998, 284 (1): 162), and T2585. Other compounds are described in WO04 / 024728, WO04 / 056823 and WO04 / 103998, all by Glaxo Group Limited. Suitable anticholinergic agents are those compounds which act as antagonists at the muscarinic receptor, in particular the compounds, which are antagonists of M receptors, or 3, double antagonists of M t / M3 or M2 / M3 < receptors or antagonists of the M? / M2 / M3 receptors. Exemplary compounds include the alkaloids of the belladonna plants as illustrated by the analogs of atropine, scopolamine, homatropine, hyoscyamine; These compounds are normally administered as a salt, which are tertiary amines. Suitable anticholinergic oxides are muscarinic antagonists, such as (3-eneO) -3- (2,2-di-2-thienylethenyl) -8,8-dimethyl-8-azoniabicyclo [3.2.1] octane iodide, bromide ( 3-eneO) -3- (2-cyano-2,2-diphenylethyl) -8,8-dimethyl-8-azoniabicyclo [3.2.1] octane, 4- [hydroxy (diphenyl) methyl] -1- bromide. { 2- [fhenylmethyl) oxy] ethyl} -1 -azonia bicyclo [2.2.2] octane, (1?, 5S) -3- (2-cyano-2,2-diphenylethyl) -8-methyl-8- bromide. { 2 - [(phenylmethyl) oxy] ethyl} -8-azoniabicyclo [3.2.1] octane, (enoO) -3- (2-methoxy-2,2-di-thiophen-2-yl-ethyl) -8,8-dimethyl-8-azonia-bicyclo-iodide [3.2.1] octane, (enoO) -3- (2-cyano-2,2-diphenyl-ethyl) -8,8-dimethyl-8-azonia-bicyclo [3.2.1] octane iodide, iodide ( enoO) -3- (2-carbamoyl-2,2-diphenyl-ethyl) -8,8-dimethyl-8-azonia-bicyclo [3.2.1] octane, (endo) -3- (2-cyano-) iodide 2,2-di-thiophen-2-yl-ethyl) -8,8-dimethyl-8-azonia-bicyclo [3.2.1] octane, and (en o) -3- bromide. { 2,2-diphenyl-3 - [(1-phenyl-methanoyl) -amino] -propyl} -8,8-dimethyl-8-azonia-bicyclo [3.2.1] octane. Suitable anticholinergics include ipratropium (for example, as the bromide), sold under the name of Atrovent, oxitropium (for example, as the bromide) and tiotropium (for example, as the bromide) (CAS-139404-48-1). Also of interest are: methantheline (CAS-53-46-3), propantheline bromide (CAS-50-34-9), anisotropin methyl bromide or Valpin 50 (CAS- 80-50-2), clidinium bromide ( Quarzan, CAS-3485-62-9), copyrolylate (Robinul), isopropamide iodide (CAS-71 -81-8), mepenzolaromide bromide (US Patent No. 2,918,408), tridihexetyl chloride (Pathilone, CAS-4310 -35-4), and hexcyclic methylsulfate (Tral, CAS-115-63-9). See cyclopentolate hydrochloride (CAS-5870-29-1), tropicamide (CAS-1508-75-4), trihexyphenidyl hydrochloride (CAS-144-11-6), pirenzepine (CAS-29868-97-1), telenzepine (CAS-80880-90-9), AF-DX 116, or methoctramine, and the compounds described in WO01 / 04118. Also of interest are revatropath (for example, as the hydrobromide, CAS 262586-79-8) and LAS-34273 which is described in WO01 / 04118, darifenacin (CAS 133099-04-4, or CAS 133099-07). -7 for the hydrobromide sold under the trademark Enablex), oxybutynin (CAS 5633-20-5, sold under the trademark Ditropan), terodiline (CAS 15793-40-5), tolterodine (CAS 124937-51-5, or CAS 124937 -52-6 for the tartrate, sold under the brand name Detrol), otilonium (for example, as the bromide, CAS 26095-59-0, sold under the name Spasmomen), trospium chloride (CAS 10405-02-4) and solifenacin (CAS 242478-37-1, or CAS 242478-38-2 for the succinate also known as YM-905 and sold under the trademark Vesicare). Other anticholinergic agents include compounds described in USSN 60 / 487,981 and USSN 60 / 511,009. Appropriate antihistamines (also referred to as HT receptor antagonists) include any one or more of the numerous known antagonists that inhibit Hi receptors, and which are safe for human use. All are reversible, competitive inhibitors of histamine interaction with Hi receptors. Examples include ethanolamines, ethyllenediamines, and alkylamines. In addition, other first generation antihistamines include those that can be characterized as based on piperizine and phenothiazines. Second generation antagonists, which are not sedatives, have a similar structure / activity relationship in which they retain the ethylene core group (alkylamines) or mimic the tertiary amine group with piperizine or piperidine. Examples of H1 antagonists include without limitation, amelexanox, astemizole, azatadine, azeiastine, acrivastine, brompheniramine, cetirizine, levocetirizine, efletirizine, chlorpheniramine, clemastine, cyclizine, carebastine, cyproheptadine, carbinoxamine, descarboethoxyloratadine, doxylamine, dimetindene, ebastine, epinastine, efletirizine, fexofenadine, hydroxyzine, ketotifen, loratadine, levocabastine, mizolastine, mequitazine, mianserin, noberastine, meclizine, norastemizole, olopatadine, picumast, pyrilamine, promethazine, terfenadine, tripelennamine, temelastin, trimeprazine and triprolidine, particularly cetirizine, levocetirizine, efletirizine and fexofenadine . Exemplary H1 antagonists are the following: Ethanolamines: carbinoxamine maleate, clemastine fumarate, diphenylhydramine hydrochloride, and dimenhydrinate. Ethylenediamines: pyrilamine maleate, tripelennamine HCl, and tripelennamine citrate. Alkylamines: clofeniramine and its salts such as the maleate salt, and acrivastin. Piperazines: hydroxyzine HCl, hydroxyzine pamoate, cyclizine HCl, cyclizine lactate, meclizine HCl, and cetirizine HCl. Piperidines: Astemizole, levocabastin in HCl, loratadine or its analogue of descarboethoxy, and terfenadine and fexofenadine hydrochloride or another pharmaceutically acceptable salt. Azelastine hydrochloride is another Hi receptor antagonist that can be used in combination with a PDE4 inhibitor. The medication, or one of the medications, may be an H3 (and / or inverse agonist) antagonist. Examples of H3 antagonists include, for example, the compounds described in WO2004 / 035556 and WO2006 / 045416. Other histamine receptor antagonists that can be used include antagonists (and / or agonists and nverses) of the H 4 receptor, for example, the compounds described in Jablonowski et al. , J. Med. Chem. 46: 3957-3960 (2003). With respect to the combination products, the co-formulation capacity is generally determined on experimental bases by known methods and may depend on the chosen type of action of the drug dispensing device. The pharmacological components of a combination product are appropriately selected from the group consisting of anti-inflammatory agents (for example a corticosteroid or an NSAI D), anticholinergic agents (eg, an M-i, M2, M? / M 2 or M3 receptor antagonist), other β2-adrenoceptor agonists, anti-infective agents (eg, an antibiotic or an antiviral), and anti-statins . All appropriate combinations are considered. Suitably, the com- patible components of coformulation comprise a β2-adrenoreceptor agonist and a corticosteroid.; and the incompatible component of coformulation comprises a PDE-4 inhibitor, an anticholinergic or a mixture thereof. Β2-adrenoceptor agonists may for example be salbutamol (for example, with the free base or the sulfate salt) or salt meterol (for example, as the xinafoate salt) or formoterol (for example, as the fumarate salt). The corticosteroid may, for example, be an ester of beclomethasone (for example, dipropionate) or a fluticasone ester (for example, propionate) or budesonide. In one example the compatible coformulation components comprise fluticasone propionate and salmeterol, or a salt thereof (particularly the xinafoatat salt) and the incompatible component of co-formulation comprises a PDE-4 inhibitor, an anticholinergic (e.g. ipratropium or tiotropi bromide o) or a mixture thereof. In another example, compatible coformulation components comprise budesonide and formoterol (eg, as the fumarate salt) and the incompatible component of co-formulation comprises a PDE-4 inhibitor, an anticholinergic (e.g., ipratropium bromide or tiotropium bromide). ) or a mixture thereof. Generally, powdered medicament particles suitable for distribution to the bronchial or alveolar region of the lung have an aerodynamic diameter of less than 10 microns, preferably between 1 and 6 microns. Other sized particles may be used if distribution to other parts of the respiratory apparatus, such as the nasal bursa, the mouth, the throat, is desired. The drug can be distributed as a pure drug, but more appropriately, it is preferred that the drugs be distributed together with excipients (vehicles) that are suitable for inhalation. The excipients include organic excipients such as polysaccharides (ie, starch, cellulose and the like), lactose, glucose, mannitol, amino acids, and maltodextrins, and inorganic excipients such as calcium carbonate or sodium chloride. Lactose is a preferred excipient. The particles of the powdered medicament and / or excipient can be produced by conventional techniques for example by micronization, grinding or sieving. In addition, the medicament and / or the excipient powder can be made with densities, dimension ranges or particular characteristics. The particles may comprise active agents, surfactants, wall-forming materials, or other components considered desirable by those skilled in the art. The excipient may be included with the medicament by well-known procedures, such as mixing, coprecipitation, and the like. Mixtures of excipients and drugs are typically formulated to allow accurate measurement and dispersion of the mixture in doses. A standard mixture, for example, contains 13,000 micrograms of lactose mixed with 50 micrograms of drug, yielding an excipient-drug ratio of 260: 1. Dosage mixtures with excipient-drug ratios of 100: 1 to 1: 1 can be used. However, at very low excipient-drug ratios, the reproducibility of the drug dose can become very variable. The medicament dispensing device described herein is in an aspect suitable for dispensing medicament for the treatment of respiratory disorders, such as disorders of the lungs and bronchial apparatus including asthma and chronic obstructive pulmonary disease (COPD). In another aspect, the invention is suitable for dispensing medicament for the treatment of a condition requiring treatment by the systemic circulation of the medicament, for example migraine, diabetes, analgesic for example, inhaled morphine. Accordingly, there is provided the use of the medicament dispensing device of the present specification for the treatment of a respiratory disorder, such as asthma or COPD. Alternatively, the present invention provides a method for treating a respiratory disorder such as, for example, asthma and COPD, which comprises administering by inhalation an effective amount of the pharmacological product as described herein from the dispensing device of the invention. medicament of the present invention. The amount of any pharmacological compound or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof is required to achieve a therapeutic effect will, of course, vary with the particular compound, the route of administration, the subject under treatment, and the disorder or disease particular treated. The medicaments for the treatment of respiratory disorders cited herein may for example, be administered by inhalation doses of 0.0005 mg to 10 mg, preferably 0.005 mg to 0.5 mg. The dose range for adult humans is generally 0.0005 mg to 100 mg per day and preferably 0.01 mg to 1.5 mg per day. It will be understood that the present description has illustrative effect only and the invention extends to modifications, variations and improvements thereof. The application of which this description and these claims form a part can be used as a basis for priority with respect to any request. later. The claims of such a subsequent request may be directed to any characteristic or combination of features described therein. They may take the form of product, process or use claims and may include, by way of example without limitation, one or more of the following claims.

Claims (54)

1. CLAIMS 1. A medicament dispensing device suitable for dispensing powdered medicament from an open blister pouch of at least one blister, the dispensing device (a) comprising a housing; (b) said housing being provided with an air inlet; (c) enclosed by said housing, a dispensing mechanism for dispensing the powdered medicament from an open ampoule bag of at least one blister that is received therefrom, and (d) associated with said dispensing mechanism and in communication with said dispensing mechanism. said air inlet, a manifold comprising (i) a body, (ii) said body defining a chimney having a chimney inlet and a chimney outlet to direct the flow of air from said chimney inlet to said chimney outlet . (iii) further defining the body a chamber having a chamber inlet and a chamber outlet, (iv) where the chimney outlet and said chamber inlet lie side by side so that when said bag The open blister of said blister is positioned adjacent thereto, said air flow can be directed from the chimney outlet to the chamber inlet by the open blister pouch to draw said powdered medicament and allow the transport of same in the blister. air flow from the chamber inlet to said chamber outlet, where during the inhalation use of the dispensing device by a patient, the air flow passes to the collector chimney only through the air inlet arranged in the housing.
2. 2. A medicament dispensing device according to claim 1, wherein the housing comprises a coupling assembly of two semi-shells.
3. 3. A medication dispensing device according to one of claims 1 or 2, wherein the air inlet is provided with a protective grid.
4. 4. A medicament dispensing device according to any of claims 1 to 3, wherein the air inlet provides the single entry point for the flow of air into the housing during the use of inhalation of the dispensing device by a patient. 5. A medicament dispensing device according to any of claims 1 to 4, wherein, apart from the air inlet, the housing provides a relatively watertight barrier at the air inlet to the air inlet. A medication dispensing device according to any of the preceding claims, wherein at least a part of the air flow flowing through the air inlet and towards the manifold chimney is directed through the chimney outlet to the blister bag open A medication dispensing device according to any of the preceding claims, wherein only a part of the air flow flowing through the air inlet and towards the chi-mene of the manifold is directed through the chimney outlet to the blister bag open A medication dispensing device according to claim 6 or 7, wherein one or more purge holes are arranged between the chimney and the chamber so that a part of the air flow (the purge air flow) will be directed towards the chamber through one or more purge holes to impact di srupively against part of the air flow carried by the entrained powdered medicament. 9. A medication dispensing device according to any of claims 1 to 8 further comprising a nozzle disposed in the manifold. 1. A medication dispensing device according to claim 9 wherein the collector is positioned within said housing in an intermediate position between said nozzle and the dispensing mechanism. eleven . A medicament dispensing device according to any of claims 1 to 10, wherein the dispensing mechanism is for the dispensing of powdered medicament from an open blister pouch of each of the blisters that are received by the same, and the manifold comprises various pairs of chimney outlet and chimney entrance, each pair being associated with an open blister pouch of one of said various blister packs. A medication dispensing device according to claim 8 or any of claims 9 to 11 when dependent on claim 8, wherein the collector is such that from 3 to 50% of a total air flow circulating through from the air inlet and towards the chimney of the collector is directed through the or each chimney outlet towards an open blister pouch and from 97 to 50% of said total air flow is directed through one or more of the chimney holes. purge towards the camera. A medication dispensing device according to claim 12, wherein the collector is arranged in such a way that in use, from 5 to 25% of a total air flow circulates through the air inlet and towards the collector chimney it is directed through the or each chimney outlet towards an open blister pouch and from 95 to 75% of said total air flow is directed through one or more purge holes towards the chamber. 14. A medicament dispensing device according to any of claims 1 to 13, wherein the manifold provides a resistance to air flow of at 5 kPa for a total air flow entering the manifold through the chimney at a rate of 60 liters /minute.
5. 5. A medication dispensing device according to claim 1, wherein the cross-sectional area of the air inlet is greater than the cross-sectional area of any part of the sump, which during inhalation use, the Air flow is expelled through the collector. 16. A medicament dispensing device according to any of claims 1 to 15, wherein the or each chimney outlet and / or chamber inlet defines an essentially circular profile and has a diameter of 1 to 7 mm. 17. A medication dispensing device according to claim 16, wherein the or each chimney outlet and / or chamber inlet is provided with a cross member extending over said substantially circular profile. 1 8. A medication dispensing device according to claim 1 7, wherein said crosspiece is cruciform in shape. 1 9. A medication dispensing device according to claims 1 to 18, wherein the chimney and the chamber are positioned side by side. 20. A medication dispensing device according to any of claims 1 to 1 9, wherein the chimney and the chamber are positioned one above the other. twenty-one . A medicament dispensing device according to claim 8 or any of claims 9 to 20 when dependent on claim 8, wherein the chimney and the chamber share a common wall and at least one of one or more purge holes are disposed in said wall common. 22. A medication dispensing device according to claim 21, wherein all of the one or more purge holes are disposed in said common wall. 23. A medication dispensing device according to claim 8 or any of claims 9 to 22 when dependent on claim 8, wherein one or more purge holes have a total cross-sectional area of 1 to 35 mm2, preferably 10 to 30 mm2. 24. A medication dispensing device according to claim 8 or any of claims 9 to 23 when dependent on claim 8, wherein one or more purge holes define a profile selected from the group consisting of circular, shaped, ovular profiles. of D or elongated slot. 25. A medicament dispensing device according to claim 24, wherein one or more purge holes define a circular or ovular profile and each has a diameter of 1 to 7 mm, preferably 2 to 5 mm. 26. A medicament dispensing device according to claim 24, wherein one or more purge holes define a D-shaped profile and each has a maximum diameter of 1 to 0 mm, preferably 3 to 7 mm. 27. A medicament dispensing device according to claim 24, wherein one or more purge holes define an elongated slot profile and each has a length of 1 to 20 mm, preferably 3 to 10 mm and a width of 0.5 to 3mm, preferably from 0.7 to 2mm. 28. A medicament dispensing device according to claim 8 or any of claims 9 to 27 when dependent on claim 8, comprising two purge holes in the form of an elongate slot disposed in parallel with respect to each other. 29. A medication dispensing device according to claim 8 or any of claims 9 to 28 when dependent on claim 8, wherein one or more purge holes are disposed adjacent the chimney outlet and / or the chamber inlet. 30. A medication dispensing device according to claim 8 or any of claims 9 to 28 when dependent on claim 8, wherein one or more purge holes are spaced from the chimney outlet and / or the chamber inlet. 31 A medicament dispensing device according to claim 30, wherein the spacing of one or more purge holes of the chamber inlet is equivalent to at least 10%, preferably at least 20%, more preferably at least 30% of the length of the chamber measured from the chamber inlet at the exit of the camera. 32. A medication dispensing device according to claim 8 or any of claims 9 to 31 when dependent on claim 8, wherein at least one of the one or more of the purge holes is directed toward an inner wall of the chamber. 33. A medicament dispensing device according to any of claims 1 to 32, wherein the collector is made of high density polyethylene. 34. A medicament dispensing device according to any of claims 1 to 33, wherein the manifold is fully or partially coated with and / or constituted of a fluoropolymeric material. 35. A medicament dispensing device according to claim 34, wherein said fluoropolymeric material comprises multiples of one or more monomer units selected from the group consisting of tetrafluoroethylene (PTFE), fluorinated ethylene-propylene (FEP), perfluoroalkoxyalkane (PFA), ethylenetetrafluoroethylene ( ETFE), vinyldienofluoride (PVDF), chlorinated ethylenetetrafluoroethylene and any mixtures thereof. 36. A medicament dispensing device according to any of claims 1 to 35, wherein said dispensing mechanism comprises: a) a receiving station for receiving the at least one blister; b) a delivery station for delivering a dose of medication other than an ampoule of at least one blister upon receipt thereof by said receiving station; c) an indexing station for individually indexing the different doses of medicament of at least one blister, where the collector is positioned to be in communication with the dose of drug releasable by said release station. 37. A medicament dispensing device according to claim 36 for use with at least one blister pack having multiple different pouches for containing different doses of medicament, wherein said pouches are spaced along the length of and defined between two separable sheets per peel fixed to each other, wherein the release station comprises a peel separator positioned to engage a base sheet and a cover sheet of a bag that has been received in said opening station to peel off such base sheet and such sheet of cover, to open such a bag, said peeling separator including a lid actuator for pulling a cover sheet and a base sheet of a bag that has been received at the receiving station. 38. A medicament dispensing device according to any of claims 1 to 37 comprising at least one blister containing medicament in powder form. 39. A medicament dispensing device according to claim 38, comprising two blisters containing medicament in powder form. 40. A medicament dispensing device according to claim 38 or 39, wherein at least one blister comprises various powdered medicament-containing ampoules disposed in a blister in the form of an elongated strip. 41 A medicament dispensing device according to claim 40, wherein said elongated strip-shaped blister comprises (a) a base sheet in which the blisters are formed to define pockets therein, each powder containing medicament; (b) a cover sheet that can be sealed to the base sheet except in the region of the ampoules and can be peeled off from the base sheet to allow release of said powdered medicament. 42. A medicament dispensing device according to any of claims 1 to 41, wherein the dispensing device is suitable for the simultaneous dispensing of powdered medicament from an open blister pouch of each of the various blister packs. 43. A medication dispensing device according to claim 38 or any of claims 40 and 41 depending on claim 38, comprising a single blister pack, wherein the powdered medicament contained therein comprises both a bronchodilator and an anti-inflammatory as components assets of the medicine. 44. A medicament dispensing device according to any of claims 38 to 42, comprising a first and a second blister, wherein the powder medicament contained in said first blister comprises a bronchodilator as an active component of the medicament and the powder medicament contained in said medicament. said second blister comprises an anti-inflammatorium as the active component of the medicament. 45. A medicament dispensing device according to any of claims 43 or 44, wherein said bronchodilator is a beta-agonist and said anti-inflammatory is a corticosteroid. 46. A medicament dispensing device according to any of claims 1 to 35 or any of claims 38 to 45 when dependent on any of claims 1 to 35, wherein the dispensing mechanism is adapted to open the or each bag of at least one blister and presenting the or each blister bag open to the chimney outlet (s) and the collector chamber inlet (s). 47. A medication dispensing device according to claim 46, wherein said dispensing mechanism comprises an indexer for indexing the bags, each time one, in the collector. 48. A medicament dispensing device according to claim 40 or any of claims 42 to 47 when dependent upon claim 40, wherein at least one blister has a portion that is adapted in use to be longitudinally separated from at least one blister to open the blisters. 49. A medicament dispensing device according to claim 48, wherein the separable portion is a first portion of at least one blister and at least one blister has, in addition, a second portion from which the first portion can be separated, being defined the blisters between the first and the second portion. 50. A medicament dispensing device according to claim 49, wherein the second portion is formed with a series of recesses along its length in which the medicament powder is contained and the first portion provides a cap for each of the holes. 51 A medicament dispensing device according to claim 48, 49 or 50, wherein the separable portion has a first and a second end that are spaced longitudinally from each other and the separable portion can be separated from at least one blister by pulling the first end lengthally along at least one blister towards the second end. 52. A medication dispensing device according to claim 39 or any dependent claim thereto, each package having at least one blister pouch, each containing an inhalable powder medicament, wherein at least one bag of the first package contains at least one medication that is not in at least one bag of the second container. 53. A medicament dispensing device according to claim 52, wherein the inhalable powder medicament in each package is for the treatment of respiratory disease. 54. Use of a medicament dispensing device according to any of claims 1 to 53 for dispensing a medicament product.