MX2008007577A - Manifold for use in medicament dispenser - Google Patents

Abstract

There is provided a manifold (450) for use in a medicament dispenser device for the delivery of medicament powder from an open blister pocket (404a,b) of a blister pack (400a,b). The manifold comprises a body, said body defining a chimney (452) having a chimney inlet (453) and a chimney exit (454a,b) for directing airflow (485) 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). 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 (485) 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 the airflow from the chamber inlet to said chamber exit. One or more bleed holes (480) are provided between the chimney and the chamber such that bleed airflow (486) may be directed into the chamber to disruptively impact the airflow (485) that transports the entrained medicament powder.

Description

DUCT FOR USE IN MEDICATION DISTRIBUTOR Field of the Invention The present invention relates to a conduit which is suitable for use in a dispenser of medicament for distributing medicament in dried powder, for example from a medicament carrier in the form of a blister-type package. The conduit aids in the effective release of medicament powder for inhalation from a patient, for example from an open blister pocket to a dispenser mouthpiece, and therefore for inhalation of a patient. BACKGROUND OF THE INVENTION The use of inhalation devices in the administration of drugs, for example in bronchodilation therapy, is well known. Such devices generally comprise a body or a housing within which a medicament carrier is located. Known inhalation devices include those in which the medicament carrier is a blister-type package containing a number of ampoule-type pockets for the containment of medicament in dry powder form. Such devices commonly contain a mechanism for accessing a dose of medicament by opening one or more blister-type pockets. The mechanism, for example, comprises perforation means or detachment means for detaching a cover sheet of a base sheet of the blister type package. The sprayed medication is then released from the open blister-type pockets for the inhaled delivery to the patient. Inhalation devices of the type described above comprise an element, generally referred to as a conduit, for guiding the flow of air into one or more open blister-type pockets to release the dust contained in the mimes; and then guiding the released powder to a mouthpiece for inhalation of a patient. It is appreciated that the characteristics of the duct are important in ensuring the effective release of the powder and subsequently in the guide of the powder released to the nozzle. The Applicant now appreciates that the shape of the conduit may affect the particle size characteristics of the powder released from medicament, whose characteristics are known to be pharmaceutically important.

Particularly, the Applicant appreciates that the fine particle fraction can be altered by the shape of the conduit. As known in the art, the "fine particle fraction" or fraction of FP generally refers to the percentage of particles within a given dose of aerosolized drug that is of a "breathable" size. It is desirable that the shape of the conduit acts such as to increase the fraction of FP of the released powder that is available in the nozzle for inhalation by the patient. The Applicant now further appreciates that the duct functioning (eg fraction of FP of the medicament powder distributed), can be influenced by the configuration of a chamber through which the drug powder released (i.e. suspended within an air flow) is transported to be available in the mouthpiece. More particularly, the Applicant now appreciates that it is beneficial for the chamber to be configured to promote the separation (eg, disaggregation or deagglomeration) of the released drug powder being transported therethrough. According to one aspect of the present invention, the duct is provided with a chimney with a chimney inlet and a chimney outlet; and a camera with a camera input and a camera output. During use, all air flow in the duct is via the chimney entrance. The chimney outlet and the chamber inlet lie side by side such that when an open blister-type pocket containing medicament powder from a blister-type package is placed adjacent thereto, at least a portion of the air flow can be directed from the chimney outlet to the inlet of the chamber via the open blister-type pocket to suspend medicament powder and allow transport thereof in the airflow of the chamber inlet to the camera entrance. To promote separation of medicament powder, one or more discharge ports are provided between the chimney and the chamber such that the flow of Discharge air can be directed into the chamber to detrimentally affect the air flow carried by the suspended medicament powder. It can be seen that, during use, the total air flow entering the chimney of the duct is "separated" in the portion that is directed in the blister-type open pocket to suspend the drug powder and in the portion that It is directed through one or more discharge orifices while the air is discharged. An advantage of the present conduit is that it can be suitably adjusted to determine the percentage of total air flow constituting each of these "separated" portions and thereby allow adequate adaptation of the conduit operation. The prior art conduits (including those described by the Patent Publications) have been described.

Previous WO98 / 30262, WO98 / 11929, WO02 / 102,444, US-A-2,587,215, US-A-5, 383,850, EP-A-1, 106,196, WO94 / 08552, WO94 / 11044, US-A-5,590,645 and US-A-5, 113,855) comprise discharge orifices in a camera or nozzle type element. These prior art ducts are designed, during use, to extract the discharge air through an air inlet that communicates directly with the external environment (i.e. directly with the outside air). BRIEF DESCRIPTION OF THE INVENTION According to one aspect of the invention, there is provided a conduit for use in a medicament dispensing device for the supply of medicament powder from an open blister-type pocket of a blister-type package, the conduit comprises a body defining a stack having a chimney inlet and an outlet of chimney to direct the air flow from the chimney inlet to the chimney outlet; the body further defines a chamber having a chamber inlet and a chamber outlet, wherein the chimney outlet and the chamber inlet are located side by side with each other such that when the open blister-type pocket of the type package Blister is located adjacent thereto, the air flow can be directed from the chimney outlet to the chamber inlet via the open blister-type pocket to suspend medicament powder and to allow transport thereof in the flow of air from the chamber inlet to the chamber outlet, and wherein one or more discharge orifices are provided between the chimney and the chamber such that the flow of suspension air can be directed into the chamber to detrimentally affect the flow of air. air that carries the powder of suspended medication. A conduit is provided which is convenient for use in a medicament dispensing device for the supply of medicament powder from an open blister-type pocket. a blister-type package. Thus, a convenient device for supplying medicament powder from an open blister-type pocket of a blister-type package is also provided, the dispensing device of the dispenser comprises a housing; wherein a dispensing mechanism for distributing medicament powder from an open blister-type pocket of a blister-type package; and a conduit are received in such a manner as described herein. The conduit comprises a body that is generally dimensioned and formed for reception by a drug delivery device, which commonly comprises a component part. The conduit by itself can be understood as a single integral component or as a partial sub-assembly or as part of an adjacent component, and is commonly formed as a molded part. In some aspects, the conduit is integral with or separable from other components of the medicament dispensing device. In one aspect, the conduit is provided as a separable component press fit to the medicament delivery device, and the conduit and / or the medicament delivery device is provided with pressure adjustment characteristics (eg located in the body of the device). distributor) to allow this adjustment mode.

Conveniently, the conduit is configured to be received by a medicament dispensing device at a location intermediate between a nozzle for the delivery of medicament in inhaled form from a patient; and an open station, in which an open blister-type pocket of the blister-type package is present for the conduit (i.e. where its medicament contents can be reached and suspended). Conveniently, the conduit is provided with pressure adjusting features to allow pressure adjustment thereof to the nozzle such as to form a conduit and nozzle sub-assembly adjusted by pressure. The body of the duct defines a chimney that has a chimney inlet and a chimney outlet. During use, air is drawn through the chimney inlet (e.g. as a result of patient inhalation) to create the air flow in the chimney. The chimney acts to direct the air flow from the chimney inlet to the chimney outlet. The body of the conduit also defines a chamber that has a chamber inlet and a chamber outlet. The air and drug powder suspended in it (see below) can be removed through the chamber inlet at the chamber outlet. A nozzle is generally located adjacent to the chamber outlet. In a particular aspect, the body part defining the chamber outlet and the nozzle comprise a common component.

The chimney outlet and the chamber inlet are located side by side with each other (i.e. adjacently or in proximity), such that when the open blister-type pocket of the blister-type package is located adjacent to them. , the air flow can be directed from the chimney outlet to the chamber inlet via the open blister-type pocket to suspend the drug powder content thereof. The transport of medicament particles suspended in such a manner in the air flow from the chamber inlet to the chamber outlet is allowed. The conduit can define more than one chimney outlet and chamber inlet and would ordinarily be where the conduit is designed for use with a medication dispensing device to distribute the medication from more than one open blister-type pocket at a time. Commonly, a chimney outlet and a chamber inlet located side by side with each other are provided to distribute the powder from each of the open blister-type pockets. In one aspect, the conduit herein is suitable for use in a medicament dispensing device for the delivery of medicament powder from an open blister-type pocket to each of the plural ampule-type packages, the conduit comprises plural pairs. of the chimney exit and chimney entrance, each of the pairs is associated with an open blister-type pocket of one of the type packages plural blister. Thus, for example in a preferred medicament dispensing device here configured to distribute the powder of a pair of blister-type open pockets, each of the pairs associated with a single blister-type pack in the form of an elongated strip, the duct It will be provided with a pair of chimney exits associated with the camera entrances, each located side by side with each other. In some aspects, the geometry of the conduit is configured such that only a ratio of the total air flow entering the conduit through the chimney inlet is directed via the chimney outlet into the open blister-type pocket. Conveniently, from 3 to 50%, preferably from 5 to 25%, more preferably from 15 to 25% of the total air flow (for example approximately 20%) is directed via the chimney outlet to the open blister-type pocket and by therefore, via the camera input in the camera. That is, from 97 to 50%, preferably from 95 to 75%, more preferably from 85 to 75% (for example approximately 80%) of the total air flow is directed through one or more discharge orifices in the chamber. In one embodiment of the invention, where the conduit is for use with two blister-type packages, such as those described below with reference to the accompanying figures, during use 80% or approximately 80% of the total air flow entering The chimney flue (through the chimney inlet) passes through the discharge orifices, the balance goes to through the open pockets. The conduit herein is convenient for use in a drug delivery device in which the patient breathes to create the air flow and the air flow is discharged through the conduit. The conduit and the drug delivery device herein are designed to be convenient for the use of a patient (eg asthmatic) with relatively poor breathing capacity. A common asthmatic patient can achieve a flow rate of approximately 30 to 100 liters / minute through a drug delivery device. Commonly, the duct provides an air flow resistance of 1 to 5 kPa (eg 2-3 kPa) for a common air flow entering the chimney of 60 liters / minute, at which flow about 10% of the flow of air is directed through the open pocket. The air flow that enters the chimney can also vary, commonly from 30 to 100 liters / minutes. It will be appreciated that during use, the pressure decreases and the flow achievable by a patient depends on the level of resistance of the airflow of the conduit and / or of the drug delivery device and the breathing capacity (respiratory effort) of the patient. As will be appreciated from the description below, one or more discharge orifices provided thereto can be particularly used to control the resistance of the total air flow of the conduit.

The resistance of the air flow of a particular drug delivery conduit and / or device can be found by dividing the square root of the pressure decrease (in kPa) by the flow rate (in liters / minutes). The low airflow resistance of the conduit and / or of the medicament delivery device is generally preferable because it allows the patient to take a deep breath and thereby transport the medicament particles (as supplied from the dispensing device) to the lung. It will be appreciated that the exact orientation of the chimney exit and the chamber inlet is determined to a degree by the shape of the blister-type pocket, and that the desired function of suspending the powder particles of medicament in the air flow be directed to the pocket. In one aspect, the blister-type open pocket has a generally elongated oval profile and the chimney outlet and the chamber inlet are located side by side with each other and during use, are placed over opposite ends of the oval open pocket profile elongate. It will also be appreciated that the shape and dimensions of the chimney outlet and the chamber inlet are determined to a degree by the shape of the blister-type pocket, and that the desired function of suspending the medicament particles in the air flow be through your pocket. It has been found that reducing the cross-sectional area of the chimney outlet and the chamber inlet can improve the performance of the fraction of FP at the expense of the increased resistance of the air flow and potentially a reduction of the operation of pocket emptying. 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 chimney exit and chamber entry are also considered to include ovular, rectangular, rectangular with rounded and crescent edges. Conveniently, the chimney of the conduit herein is arranged to create turbulence in the airflow in the blister-type open pocket. That is, the chimney is configured such that during use the turbulent air flow is present in the open blister-type pocket. Such a turbulent air flow has been found to aid in suspending the medicament powder content of the blister-type open pocket, and thereby helping to flush the medicated powder content from the pocket.

In one aspect, turbulence occurs as a result of the creation of cutting voltage, which aids in the suspension of medicament powder by the air flow. The cut-off voltage is generally defined to mean the normal speed gradient for the direction of the air flow. Thus, a high-voltage cutting region ("high cut") is one in which there is a relatively large velocity gradient with respect to a relatively short distance. The Applicant believes that the presence of such turbulence may it is particularly beneficial where the medicament powder comprises the non-cohesive powder components (for example, one that is non-tacky or is only lightly associated for example not agglomerated). The well-known Carr index can be used to quantify the cohesiveness of a particular powder for delivery by the conduit and the medicament delivery device herein. The methods for measuring the Carr index are described in the following 5 references: Carr, R L (1965) 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 herein, turbulent flow is created in the open blister-type pocket providing plural chimney outlets to the chimney, which direct airflow into the open blister-type pocket. In a particular aspect, the plural chimney outlets are located such that during use the plural air flow jets are directed together to produce a turbulent interaction (e.g. high cut). The plural chimney outlets (and therefore, the plural airflow jets) are conveniently located at an angle (?) Relatively to each other where? it is commonly from 150 ° to 30 °, preferably from 120 ° to 60M. In another aspect herein, the turbulent flow is created in the open blister-type pocket forming the chimney and / or the chimney outlets to produce a non-linear air flow. In a particular aspect, the chimney and / or the chimney outlets are formed to produce a helical (e.g. vortex-like) air flow that is intrinsically turbulent. In a further aspect herein, an obstacle is placed within the chimney and / or chimney outlet to detrimentally create a non-linear air flow. In a particular aspect, a transverse piece or a divider (for example in the form of a knife) is provided inside the chimney and / or at the chimney outlet to interrupt the flow of air and to produce turbulent high voltage cutting regions. Conveniently, the chimney of the conduit herein is configured to create regions of acceleration or deceleration in the air flow in the blister-type open pocket. That is, the chimney is configured such that during use, the acceleration or deceleration airflow is present in the open blister-type pocket. Such an accelerating or decelerating air flow (whether turbulent or not) aids in suspending the medicated powder content of the open blister-type pocket, and thereby helps to flush the medicated powder content from the pocket. The chimney outlet and the chamber inlet may each comprise one or more single openings (ie openings) or alternatively, in some aspects, certain features may be provided thereto including a "part". "cross" (for example in the form of a cross) provided in the openings of one or both of them Conveniently, the chimney and the duct chamber are configured to be side by side with each other or one on top of the other as a assist the requirements for (i) the chimney outlet and the chamber inlet to be placed side by side with each other and (ii) so that one or more discharge orifices are provided between the chimney and the chamber, as now described in more detail. The conduit herein provides that the suspended medicament powder is transported via the chamber by the air flow from the chamber inlet to the chamber outlet. One or more discharge orifices (or passages / channels) are provided between the chimney and the chamber such that the flow of suspension air can be directed into the chamber to affect in a damaging manner the airflow carried by the suspended medicament powder . The presence of one or more of the so-called discharge orifices improves the overall performance (eg operation of the FP fraction) of the conduit. Particularly, it is beneficial that the discharge airflow promotes the separation (for example to disaggregate or de-agglomerate) of the drug powder suspended in the chamber. Particularly, exposing the suspended medicament powder to the regions of different strength that occur as a result of the introduction of the discharge airflow of the fireplace to the chamber to help promote the separation of the desired dust in the chamber. The promotion of such separation can be particularly beneficial where the medicament powder comprises the cohesive powder components (for example one comprising the particles that tend to associate with each other or one in which the particles agglomerate). Conveniently, one or more discharge orifices are provided to a wall that is common (and acts as a divider between) the chimney and the chamber. Conveniently, the chimney and the chamber share a common wall and at least one of, preferably all of, one or more discharge orifices are provided to the common wall. One or more discharge orifices commonly have a total cross-sectional area (i.e. the cross-sectional area of all discharge ports aggregated together) of 1-35 mm2, preferably 10-30 mm2, more preferably 15-25 mm2. One or more discharge ports can define any convenient profile including an oval, circular, D-shaped and elongated slot. In one aspect, one or more discharge orifices are circular or oval or each discharge orifice has a diameter of 1-7 mm, preferably 2-5 mm. In another aspect, one or more discharge orifices are D-shaped and have a maximum diameter of 1-10 mm, preferably 3-7 mm. In other aspect, one or more discharge orifices 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 discharge orifices arranged in parallel are provided between the chimney and the chamber. Preferably, the discharge holes in the form of a parallel elongated slot are located parallel to the air flow within the chamber. In one aspect, one or more discharge ports are provided adjacent (i.e. in proximity) to the chimney outlet and / or the chamber inlet. In another aspect, one or more discharge ports are separated from the chimney outlet and / or the chamber inlet. Commonly, the separation of one or more discharge orifices from the chamber inlet amounts to at least 10%, preferably to at least 20%, more preferably to at least 30% of the length of the chamber measured from the inlet from camera to camera output. In one aspect, one or more of the discharge orifices are directed towards a wall of the chamber, thereby creating a high-cut region near the wall and causing the particles to collide with the wall. Preferably, the overall geometry of the chamber is configured for example to direct the air flow in these high cut regions and / or to cause collisions with the wall. An additional advantage of directing the discharge air into the walls of the conduit is to prevent deposition of the medicament particles therein. Where the plural discharge orifices are provided, they are conveniently directed to each other such that the resulting discharge jets interact with each other to create high cut regions. Preferably, the total geometry of the chamber is configured for example to direct the air flow in these high cut regions. Conveniently, during use, one or more discharge ports direct one or more air jets to affect at least one internal surface of the chamber to create at least one high cut zone therein, more than 3 Pa to an index of 60 liters / minute air flow for the air entering the chimney. Conveniently, during use, the medicament powder from the pocket is directed in at least one high cut zone within the chamber to separate any agglomerated particle component therefrom. Conveniently, during use, at least one high cut area acts for example to reduce the deposition of dust on at least one internal surface of the chamber. It will be appreciated that the arrangement of one or more discharge orifices also results in a reduced resistance of the air flow due to an air flow ratio (as extracted). originally inside the fireplace) is not removed through the open blister-type pocket. The arrangement of the discharge orifices can therefore potentially affect the efficacy of emptying the medicament content of the open blister-type pocket. Therefore, a compromise between the creation of accelerating air flow regions must be forceful by providing one or more discharge orifices (good for separating the dust in the chamber) and reducing the airflow resistance (and potentially affecting the emptying of the pocket). As a general rule, the airflow resistance of the duct should not be reduced below a level where pocket emptying is compromised at a minimum flow rate of 30 liters / minute for the air entering the chimney. Commonly, the conduit in the present is configured such that from 3 to 50%, preferably from 5 to 25%, more preferably from 15 to 25% (for example approximately 20%) of the air flow entering the chimney inlet, be directed via the chimney outlet to the open blister-type pocket. The rest of the air flow (for example about 80%) therefore does not go into the open blister-type pocket and rather passes through one or more discharge ports to the chamber. In general terms, for a cohesive powder it is desirable that less air flow is directed through the pocket than for a very cohesive powder. In some aspects in the present, the size and / or the location of any inlet, outlet and / or one or more discharge ports in the conduit are adapted to achieve the desired level of airflow through the pocket and / or airflow resistance and / or cut within the conduit, during the use. It will be appreciated that such an adaptation may consider the cohesiveness or otherwise the medicament powder to be delivered through the conduit. In addition, the separation of the powder in the chamber can be further promoted if the geometry and shape of the chamber are self-configuring, to create regions of high differential force (eg high cut). Suitable high cut regions can be created if the diameter and / or shape of the chamber conveniently varies along its length (ie along the path of the air flow that is defined) such that the flow of air and suspended dust that flows through them tend to find the walls of the chamber. Such encounters with the walls are always regions of high cut (ie high speed or air flow after low air flow velocity) because in the wall itself the velocity of the air flow is effectively zero. In another aspect, the separation of the powder can be further promoted in the chamber, if the chamber is configured such that the regions of acceleration or deceleration of air flow are created therein. That is, dust separation is promoted if an airway and suspended dust experience a region of air flow of acceleration or deceleration when passing through the chamber. Preferably, the overall geometry of the chamber is configured such as to direct the air flow that carries the suspended particles in these regions of accelerating air flow. It will be appreciated that during use, the presence or otherwise the airflow of acceleration or deceleration in the conduit herein may depend on the inhalation profile of the patient or the geometry of the conduit. 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 one hand, a conduit geometry that (for any patient inhalation profile) results in slow-moving air flow regions that are created adjacent to fast-moving air flow regions results in a desired region of acceleration air flow. Alternatively, the conduit may be provided with features such as fins or valves that open in response to a particular airflow pressure thereby creating a zero flow "acceleration" (ie fin or valve closed) for the permitted flow ( that is, fin or valve open). Conveniently, during use, the conduit is configured to modify the effect of a user's inhalation profile to increase the acceleration experienced in the powder when it is aerolized in the blister-type pocket. Conveniently, during use, the conduit is configured to modify the effect of a user's inhalation profile to increase the acceleration experienced in the powder as it travels through the blister-type pocket chamber to the patient. The improved predisposition for a given profile of inhalation of a patient to give rise to regions of accelerating airflow, can be conveniently created if the cross-sectional area (eg diameter) of the chamber is reduced in the direction of flow. It will be appreciated that a smaller cross-sectional area means that the air has a higher velocity for a given flow rate. The acceleration for a given inhalation profile will therefore be proportionally greater. Convenient regions of the acceleration or deceleration airflow can also be created in the conduit if the cross-sectional area (eg diameter) of the chamber is configured to vary in diameter, for example to narrow along its length (i.e. along the path of the air flow that defines it), such that the air flow and the suspended dust flowing through them meet with a narrower or alternatively wider cross section along their length (ie along the path of the airflow that defines it), such that the airflow and suspended dust flowing through them meet with a wider cross section. It will be appreciated that any reduction of the cross-sectional area of the chamber will also result in increased resistance of the air flow, and therefore may potentially affect the efficiency of emptying the medicament content of the open blister-type pocket. Therefore, a compromise between creating regions of accelerating air flow by reducing the cross-sectional area of the chamber (good for dust separation) and increasing the resistance of the air flow (and potentially affecting pocket emptying) must be conclusive. In one aspect, the diameter of a chamber of the circular profile is narrowed from about 14-16 mm at the end of the chamber inlet to about 5-8 mm at the end of the chamber outlet. In another aspect, the diameter of a chamber is about 5-7 mm across its entire length (compared to a conventional diameter of about 14-16 mm). In a further aspect, the dust separation can be further promoted in the chamber if the chamber is configured such that mechanical obstacles are created therein. That is, dust separation is promoted if a suspended air / dust flow experiences mechanical obstacles as it flows through the chamber. The convenient mechanical obstacles that can be provide the camera comprise or consist of deflectors, propellers, blades, blades and diffuser forms. Alternatively, the chamber itself can be formed with features (e.g., with defined surface notches or projections) that provide mechanical obstacles. The operation of the conduit can be further improved if the conduit is configured such as to delay the emptying of the medicament powder content from the ampule-like pocket. In one aspect such a delay is achieved by reducing the amount of air passing through the open blister-type pocket. Such reduction, however, should not be too great since insufficient air flow through the pocket can prevent complete emptying of the medicament content from the open blister-type pocket. Such reduction of air flow through the blister-type open pocket is achieved by providing the conduit with one or more discharge ports positioned such as to "deflect" the air flow from the open pocket. The operation of the conduit can be improved where the conduit is configured to delay the emptying of medicament powder content from the blister-type pocket until the differential force regions (eg high cut / acceleration air) capable of causing separation of the dust is believed in the camera. If the pocket empties too soon the dust Once it is separated, it will have passed through the high differential force areas before they are established to delay the emptying of the pocket, the operation of the duct will be improved by ensuring that more dust experiences a high cut region. Conveniently, the conduit here is configured for example to delay the emptying of medicament powder content from the blister-type pocket until a predetermined flow rate through the conduit chamber (ie not only through the pocket of blister type) is reached by the inhaling patient. While the value for the predetermined flow rate can be conveniently adapted, it is generally desirable to have a value between 5 to 45 liters / minute, preferably 20 to 30 liters / minute. Desirably, the conduit herein generally acts such as to improve the uniformity of the dosage of medicament delivered in such a manner. Desirably, the conduit herein acts completely such as to increase the emitted dose (ED) of drug powder that is available at the chamber / nozzle outlet for inhalation by the patient. The ED is generally measured by collecting the total amount of drug powder emitted from the dispensing device for example, using a dose sampling apparatus such as a Dose Uniformity Sampling Apparatus. The ED also it can be expressed as the percentage (% of ED) of measured dose (MD) contained within the particular ampoules from which the drug powder is released. Thus, in this case, the% of ED is calculated as (ED / MD) x 100%. It is desired that the% ED be at least 95% by weight, preferably more than 98% by weight. Desirably the conduit here also acts to increase the fraction of FP of the medicament powder that is available in the chamber / nozzle outlet for inhalation by the patient. The term "fraction of fine particle of emitted dose" or fraction of FP (ED) refers to the percentage of particles within a given emitted dose of aerosolized drug that is of a "breathable" size, with respect to the total emitted dose . A range of particle size of 1-6 μm is considered to be generally "breathable" in size. The fraction of FP (ED) can be calculated as a percentage of emitted dose. Thus, in this case, the fraction of FP (ED) is calculated as (FPF / ED) x 100%. It is desired that the fraction of FP (ED) be at least 25% by weight, preferably more than 30% by weight of the emitted dose of particles available at the chamber / nozzle outlet. The FP fraction can also be defined as a percentage of the measured dose contained within the particular ampoules from which the medicament powder is released. Thus, in this case, the fraction of FP (MD) is calculated as (FPF / MD) x 100% It is desired that the fraction of FP (MD) be at least 25% by weight, preferably more than 30% by weight. The conduit herein is commonly provided (as a component part thereof) for a medicament dispensing device that is configured to receive a blister-type package having one or more blister-type pockets containing medicament in dry powder form. Conveniently, the medicament dispensing device comprises a housing, which may have any convenient profile or shape. One preferred form is that of a shell-like housing formed by a coupling assembly of two cover halves, which can be hinged or alternatively be completely separable from each other. The housing is formed of any convenient material, but very commonly comprises a polymeric plastic material that is relatively robust but is also easily manufactured by a manufacturing process by volume. The accommodation is conveniently provided with an air intake. This commonly takes the form of a hole or holes of suitable shape and size provided in the wall of the housing. The air inlet is conveniently positioned such as to be located in a position that would not be commonly covered or blocked by the fingers and / or thumbs of a user during normal use thereof. The air inlet is conveniently covered at least in part, by the protective grille or other feature that acted such as to prevent clogging and / or minimize the undesirable entry of dirt and other particulate contaminants thereto. Conveniently, included by the housing, a dispensing mechanism for dispensing medicament powder from an open blister-type pocket of at least one ampule-type package is provided in such a manner. The details of the convenient distribution mechanisms are provided by the subsequent description. Associated with the distribution mechanism and in communication (fluid communication / air flow) with the air inlet, a conduit is provided in the present. Conveniently, the medicament dispensing device provides for the air flow to be drawn into the chimney of the duct only through the air inlet provided in the housing. That is to say, all the air that flows in the duct does it via the air inlet and the flue chimney. Thus, during such use the patient inhales through the mouthpiece, which negative pressure in the duct, which causes the air to be extracted out of the distributor device through the air inlet and into the chimney of the duct via the inlet of chimney, which is in fluid communication with (for example juxtaposed to) the air intake. At least part of the The air flow is then directed from the chimney outlet to the chamber inlet via the open blister-type pocket to suspend the drug powder content thereof. Preferably, the air inlet provides the single entry point for air flow in the medicament dispensing device, and particularly to the open blister-type pocket of the blister-type package, during the inhaled use of a patient's distributing device. Thus, no other air inlet or other air inlet point is conveniently provided in the housing and the housing itself provides relatively a relatively tight air barrier for the intake of outside air thereto by any other means. Conveniently, the transverse air inlet area provided in the housing of the drug delivery device is larger than (eg, at least one and a half times, preferably twice) the cross-sectional area of any part of the duct, which incoming air will experience (descending) in the conduit. Thus, the cross-sectional area of the air inlet is conveniently greater than any cross-sectional area of the chimney; the total cross-sectional area of the chimney outlet and one or more discharge orifices; and the cross-sectional area of the camera. The rationale of this is that the air inlet therefore can not act such as limiting or otherwise affecting the nature of the air flow through the air. distributing device and thus, all the control of the air flow (and air pressure, etc.) is as a result of the geometry and location of the conduit (including the selection of the transverse areas for any part of the conduit). In one aspect, the blister-type package comprises multiple ampoules for the containment of medicament product in dry powder form. The ampoules are commonly configured in the regular manner to facilitate the release of the medication from them. The ampoules can have any convenient shape including those with a square, circular, oval or rectangular profile. The particular shape, including the shape and transverse area, of the blister-type pocket affects the characteristics of the air flow, and particularly the resistance of the air flow and the pressure decrease experienced in the open pocket when a patient inhales through the duct at the moment. As an example: a common dose of medicament powder in a blister-type pocket is 17 μl. If the pocket took the shape of a sphere, to accommodate this dose would have a radius of 1.7 mm and a cross-sectional area of 80 mm2. A flow of 60 l / min through an area of 8 mm2 equals an average speed of 125 m / s. The decrease in pressure due to this flow will be approximately equal to: (where p = air density = 1.3 kg / m3, V = average speed = 125 m / s and K = a geometric factor). For a sudden contraction of a large cross section of 8.0 mm2, K = 0.5 (approximately) thus the pressure drop will be 5.1 KP. For a sudden expansion of 8.0 mm2 at a large cross-sectional area K = 1 (approximately) so the pressure drop will be 10.2 kPa. Thus, a pocket geometry with an input of 8.0 mm2 and an output of 8.0 mm2 would have a resistance of 15.3 kPa to 60 liters / minutes. The pocket strength is = V (15.3) / 60 = 0.065 (kPa) 0 5 min / l so for a pressure decrease of 2 kPa, the flow would be = V (2) /0.065 = 22 l / min, This is about 1/3 of the total flow. In the case of a blister-type pocket suitable for use with the well-known Diskus device (registered trademark) as sold by GlaxoSmithKIine Pie, and as described in detail herein, the medicament powder is more compressed (not in a sphere), the cross section in the pocket is in the region of 4 mm2 so the average speed at 60 liters / minute would be 250 m / s. For a simple input-output system (as above) the pressure drop at 60 liters / minute would be 61.2 kPa, the resistance would be 0.130 (kPa) 0 5 minutes / liters and the flow for a pressure decrease of 2 kPa It would be 11 liters / minutes (18% flow). For a blister-type pocket suitable for use with the well-known Diskus (trademark) device, the resistance would be approximately 0.15 (kPa) 0 5 minutes / liters and the flow for a pressure decrease of 2 kPa would be 9.4 liters / minutes (16% flow of 60 liters / minutes). In one aspect, the multi-dose ampule-type package comprises the plural ampules located in a generally circular fashion in a disc-shaped blister-type package. An example of a convenient drug dispensing device for distributing medicament powder from such a disc-shaped blister-type package is the well-known Diskhaler device (trademark) as sold by GlaxoSmithKine Foot. In another aspect, the elongated shaped blister pack, for example, comprises a strip or tape.

Preferably, the blister-type package is defined between two members releasably secured together. U.S. Patent Nos. 5,860,419, 5,873,360 and 5,590,645 in the name of Glaxo Group Ltd, describe drug packages of this general type. In this aspect, the device is generally provided with an open station comprising detachment means for detaching the members apart to have access to each dose of medicament.

Conveniently, the drug delivery device is adapted for use where the members Detachable are elongated sheets defining a plurality of separate medication packages along the length thereof, the device is provided with indexing means to in turn index each package. Preferably, the medicament dispensing device is adapted for use where one of the sheets is a base sheet having a plurality of pockets therein, and the other of the sheets is a cover sheet, each pocket and the adjacent part of the sheet. the cover sheet respectively define one of the packages, the medicament dispensing device comprises the driving means for separating the cover sheet and the base sheet in the opening station. An example of the drug delivery device of this type is the well-known Diskus device (trademark) as sold by GlaxoSmithKIine Pie. In one aspect, the ampule-shaped medicine package comprises (a) a base sheet in which the ampoules are formed to define pockets therein that contain a medicament formulation of inhalable dry powder; (b) a cover sheet that can be sealed with the base sheet except in the region of the ampoules and is mechanically removable from the base sheet to allow release of the medicament formulation of inhalable dry powder, wherein the base sheet and / or the cover sheet have a laminated 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 commonly sealed to each other over their full width except for the front end portions where they do not commonly seal together at all. Thus, the front end portions spaced apart from the base and cover sheet are presented at the end of the strip. Conveniently, 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 conveniently measured by the ASTM test method No. ASTM E96-635 (E). Conveniently, the polymeric material comprises a material selected from the group consisting of polypropylene (for example in a oriented or molded 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; and olefin cyclic polymer. Conveniently, the cover sheet comprises at least the following successive layers: (a) paper; attached to (b) the plastic film; attached to (c) aluminum foil. The aluminum foil is commonly covered with a layer (for example hot lacquer, film or extrusion coating) to join the base sheet material.

The thickness of each of the cover sheet layers can be selected according to the desired characteristics but is commonly in the order of 5 to 200 microns, particularly 10 to 50 microns. The plastic layer is in one aspect, suitably selected from polyester (non-oriented, monaxially oriented, or biaxial), polyamide, polypropylene or PVC. In another aspect the plastic film is a oriented plastic film, suitably selected from oriented polyamide; oriented polyester (OPET); and oriented polypropylene (OPP) The thickness of the plastic layer is commonly 5 to 40 μm, particularly 10 to 30 μm. The thickness of the aluminum layer is commonly 10 to 60 μm, particularly 15 to 50 μm such as 20 to 30 μm. In some aspects, the paper layer comprises a paper / extrusion layer, laminated optimally to aluminum. In a particular aspect, the cover sheet comprises at least the following successive layers: (a) paper; joined (b) to the polyester; bonded (c) to aluminum foil; which is coated with a hot-seal lacquer to join the base sheet. The thickness of each layer can be selected according to the desired characteristics but is commonly in the order of 5 to 200 microns, particularly 10 to 50 microns. The bond in aspects can be provided as an adhesive bond (for example solvent based adhesive where the solvent is organic or water based); Adhesive bond without solvent; laminated bond by extrusion; or calendared by heat. Conveniently, the base sheet comprises at least the following successive layers: (a) oriented polyamide; adhesively bonded (b) to aluminum foil; adhesively bonded (c) to the 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 joined with the cover sheet, which is usually treated with a hot-seal lacquer. The thickness of each non-polymeric base sheet layer can be selected according to the desired characteristics but is commonly in the order of 5 to 200 microns, particularly 20 to 60 microns. According to the invention, the thickness of the polymer layer is selected to reduce the humidity input, and is from 10 to 60 microns, particularly from 25 to 45 microns, preferably from 30 to 40 microns. Conveniently, the polymeric material is selected from the group consisting of polypropylene (in oriented or molded form, standard or metallocene); polyvinyl chloride (PVC); polyethylene (in the form of high, low or intermediate density); polyvinylidene chloride (PVDC); polychlorotrifluoroethylene (PCTFE); cyclic olefin copolymer; and olefin cyclic polymer.

Optionally, other layers of material are also present.

The various known techniques can be used to attach the cover sheet and the base and therefore seal the blisters. Such methods include adhesive bonding, radiofrequency casting, ultrasonic casting and hot rod sealing. The base sheet herein is particularly convenient to be formed by "cold form" methods, which are conducted at lower temperatures than conventional methods (e.g. at about room temperature). Such "cold form" methods are of particular utility where the medicament or medicament formulation for containment within the ampule is sensitive to heat (eg degrades or denatures upon heating). The blister-type package is conveniently admissible by a medicament dispenser comprising the conduit herein which also comprises a housing for receiving the package. In one aspect, the medicament dispenser has a unitary form and the housing is integral therewith. In another aspect, the medicament dispenser is configured to receive a replacement cartridge and the housing is part of the replacement cartridge. Conveniently, the interior of the housing is formed, or alternatively provided with the specific guide features, to direct the ampule-shaped medication package appropriately into the housing. In particular, the The guide should ensure that the blister-type package is conveniently located to interact with the internal mechanisms (for example, the indexing and opening mechanisms) of the housing. Conveniently, the drug delivery device has an internal mechanism for distributing the various doses of dry powder medicament carried by the ampoules of the ampule-type package for administration to the patient (for example by inhalation). Conveniently, the mechanism comprises, a) a receiving station for receiving the blister-type package; b) a release station for releasing a different dose of medicament from a vial of the blister-type package upon receipt thereof by the receiving station; and c) an indexing station for individually indexing the different drug doses of the blister-type package, wherein the conduit here is positioned so as to be in communication with the dose of releasable medicament by the release station. The mechanism comprises receiving means (e.g., a receiving station) for receiving the blister-type package. The mechanism also comprises release means for releasing a different dose of medicament from a blister of the blister-type package to be received by the receiving station. The release means commonly comprise means for mechanically detaching the strip from the ampoule. A conduit here is positioned to be in communication with the different doses of drug powder releasable by the delivery means. The delivery of the medicament so released to the patient for inhalation in such a manner is preferably through a single outlet which communicates with or forms an integral part with the conduit. The output can have any convenient 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 an injector for the insertion in the nasal cavity of a patient. The mechanism also comprises indexing means for individually indexing the ampoules containing the different dose of medicament from the ampule-shaped medication package. Indexing commonly occurs sequentially, for example by accessing the dose portions sequentially located along the length of the ampule-shaped medication package. Optionally, the medicament dispenser also includes counting means for counting each time a different dose of medicament from the ampule-shaped medication package is indexed by the indexing means.

In one aspect, the counting means is configured to count each time a different dose of drug from the drug carrier is indexed by the indexing means. Conveniently, the indexing means and the counting means are coupled directly or indirectly (for example via a coupler) to each other to allow counting of each indexing. Conveniently, the counting means are provided (or communicated with) an exhibitor to display to the patient the number of different doses that were missed or the number of doses taken. In a preferred aspect, the medicament dispenser takes the form of a dispenser for use with a package of medicament in the form of an ampoule herein having multiple distinct pockets for containing inhalable doses of medicament, wherein the pockets are separated as Along the length of and defined between two detachable sheets secured to each other, the dispenser has an internal mechanism for distributing the doses of medicament contained within the medication package, the mechanism comprising, a) an opening station for receiving a pocket of the medication package; b) a detaching device positioned to attach a base sheet and a cover sheet of a pocket that has been received in the opening station to detach such a sheet base and such cover sheet, for opening such a pocket, the release means include a cap drive for separating a cover sheet and a base sheet from a pocket that has been received at the opening station; and c) an indexing station for individually indexing the distinct pockets of the medicament package, wherein the conduit herein is positioned to be in communication with an open pocket through which the dose of medicament is available from such an open pocket. Conveniently, the indexing means comprise a rotating indexing wheel having slits therein, the indexing wheel is engageable with a medication package, during use, with the medicament dispenser such that the slits each receive a respective pocket of the base sheet of a blister strip during use with the medication dispenser. According to another aspect of the present invention, there is provided a medicament dispenser comprising (eg, loaded with) at least one ampule-type package containing dry powder medicament herein. The conduit herein has been described above in terms of its use with a convenient drug dispensing device for dispensing medicament from the open pocket of a blister-type package. It will be appreciated that the conduit can also be used for use with any convenient drug dispensing device for dispensing medicament from an open cavity, wherein the cavity can for example be provided by an open capsule of a capsule-shaped package. Thus, according to a further aspect of the invention there is provided a conduit for use in a medicament dispensing device for the delivery of the medicament powder from an open cavity of a medicament package, the conduit comprises a body, which defines a fireplace that has a chimney inlet and a chimney outlet to direct the air flow from the chimney inlet to the chimney outlet; the body further defines a chamber having a chamber inlet and a chamber outlet, wherein the chimney outlet and the chamber inlet are located side by side with each other such that when the open cavity is located adjacent to the same, the air flow is directed from the chimney outlet to the chamber inlet via the open cavity to suspend medicament powder and to allow transport thereof in the air flow from the chamber inlet to the chamber outlet , and wherein one or more discharge orifices are provided between the chimney and the chamber such that the discharge air flow can be directed into the chamber to detrimentally affect the air flow that carries suspended drug powder.

Conveniently, the medicament dispenser herein is packaged within a package (i.e. an external package, e.g. in the form of an overwrap) comprising a packaging material that is designed to reduce the ingress of ambient moisture to the dispenser (and package of medication of the same) packaged by the same.

The package is conveniently formed of any material that is impermeable or substantially impervious to moisture. The packaging material is preferably permeable to volatiles that can escape from the plastics that form the body of the inhaler and / or the ampule-shaped medicine package, by diffusion or otherwise, thereby preventing an accumulation of pressure . Additional aspects and features of the invention are described in the appended claims, and in the following detailed description of the 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-type package 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 is suitable for adaptation according to the present invention; Figure 3a shows a highly schematic sectional side view of the base unit of a second drug delivery device comprising a pair of medicament carriers of Figure 1 and convenient for use in accordance with 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 the sequential stages of the perspective view for preparing a third drug delivery device for the use of a patient distribution, the device contains a pair of drug carriers of Figure 1; Figures 5a to 5c show the corresponding sequential steps of the side view for preparing the third drug delivery device for use where the dispensing device is shown without a part of its external housing; Figure 6 shows in an exploded perspective view, a gear mechanism of the third drug delivery device; Figures 7a to 7c show details in the side view of the gear mechanism when it is ready for use in the sequential stages corresponding to Figures 4a to 4c and 5a to 5c; Figure 8 shows in perspective side view, a detail of a ratchet "anti-return" mechanism of the third drug delivery device; Figure 9 shows in perspective side view, the dispensing mechanism and the medicament carriers of the third drug delivery device; Figure 10 shows a partially exploded view of the third drug delivery device, without its nozzle; Figure 11 shows a side view of one half of the cover housing of the third drug delivery device having a conduit provided thereto; Figure 12 shows a cut-away view of the third drug delivery device; Figure 13 shows a cut-away view of a nozzle assembly and a first conduit of the third drug delivery device; Figure 14a shows a side view of the first conduit in Figure 13; Fig. 14b is a cross-sectional side view of the first conduit taken on the line XlVb in Fig. 15b showing its relation "during use" with the medicament carriers of the third distributing device of medicine; Figures 15a and 15b are cross sectional planar views of the first conduit taken on the lines XVa and XVb in Figure 14a illustrating respectively the flow of primary air and discharge through it during inhalation by a patient in the mouthpiece of the third medication distributor device; Fig. 15c is a cross-sectional schematic side view of the first conduit taken on line XVc in Fig. 14b showing the flow of primary air and discharge through it during inhalation of the patient into the mouthpiece of the third drug delivery device; Figure 16a shows a side view of an alternative conduit convenient for use in the nozzle and duct assembly of Figure 13; Fig. 16b is a cross-sectional side view of the alternative conduit taken on line XVIb in Fig. 17b showing its relation "during use" with the medicament carriers of the third drug delivery device; Figure 17a shows a cut-away view of the nozzle assembly and the alternative conduit of the third drug delivery device; and Figures 17b and 17c are cross-sectional plan views of the alternative conduit taken in the lines XVI I b and XVIIc in Figure 16b illustrating respectively the flow of primary air and discharge through it during inhalation by a patient in the nozzle of the third drug delivery device. Detailed Description of the Invention Figure 1 shows a medicament carrier 100 having the shape of an elongated blister-type strip. The medicament carrier 100, which is of the type used in the dry powder inhaler DISKUS® ADVAIR® of GlaxoSmithKIine Pie, comprises a flexible strip 102 defining a plurality of pockets 104 each of which contains a dose (or portion thereof). same) of inhalable drug powder 20. Strip 102 is flexible enough to be rolled on a roller, as shown in Figure 1. Strip 102 comprises a base sheet 110 in which ampoules 106 are formed, by forming in cold or deep extraction, to define the pockets 104 and a cover sheet 112 which is hermetically sealed to the base sheet 110, except in the region of the ampoules 106, to hermetically cover the pockets 104. The hermetic seal of the base sheets and cover 110, 112 is such that base and cover sheets 110, 112 can be peeled off to open pockets 104 to access the medicament powder. The sheets 110, 112 are sealed together over their entire width except for the main end portions 114, 116 where nothing is they preferably seal with each other. The cover sheets 112 and base 110 are each formed of plastics / aluminum laminate and adhered to each other by hot sealing. The cover sheet 112 comprises at least the following successive layers: (a) paper; adhesively bonded (b) to the polyester; adhesively bonded (c) to aluminum foil; which is coated with a hot-seal lacquer to join the base sheet. The base sheet 110 comprises at least the following successive layers: (a) oriented polyamide; adhesively bonded (b) to aluminum foil; adhesively bonded (c) to the third layer comprising a polymeric material (e.g. polyvinyl chloride). Alternatively, the cover sheet 112 can be constructed as described in International Patent Application No. PCT / US06 / 37438 filed on September 26, 2006, the entire contents of the International Application, and its Application for the North American National Phase of Counterpart, is incorporated herein by reference. The pockets 104 are identical to each other and, with the exception of a test pocket 108 at the leading end of the strip 102, are equi-separated along the length of the strip. The pockets 104 are elongated and extend transversely with respect to the length of the strip 102. This is convenient because it allows a large number of pockets 104 to be provided over a given length of the strip. Strip 102 can, for example, be provide with thirty, sixty or hundreds of pockets 104, but it will be understood that strip 102 can have any convenient number of pockets 104. Additional details of strip 102 can be found in US Patent No. 5,590,645, the entire contents of which are incorporated hereby in the present by reference. In the embodiments of the present invention, the following examples herein, such plural strips 102 are used in a single drug delivery device, wherein each strip provides the drug dose component portions of a combination drug product. Each strip 102 can be of the same size and / or contain the same amount of dose (for example volume or mass) or in alternative embodiments, the strips which are of different sizes and / or contain different amounts of doses can be used in the combination. Figure 2 shows a first dispensing device for manually operable and hand held medicament in the form of a dry powder inhaler which can be adapted to comprise a conduit according to the present invention. The inhaler 220 is of a general type sold by GlaxoSmithKIine Foot under the trademark DISKUS®, the details of which are described in US Patent No. 5,590,645 above, particularly with reference to FIGS. 13 to 16 of FIG. same The inhaler 220 contains the medicament carrier of Figure 1, here designated 202 with the other characteristics of the strip that are assigned with similar numbers. In more detail, the inhaler 220 is configured to deliver unit doses of medicament powder from the pockets 204 of the ampule-type elongate strip 202. The inhaler is comprised of an outer box 221 that houses the drug strip 202 within the body 222. The patient uses the inhaler holding the device 220 in his mouth, operating the lever 224, and inhaling through the nozzle 226. Actuation of the lever 224 activates the internal mechanism of the inhaler, such that covering sheets 212 and base 210 of the rolled-up drug-type blister strip 202 are separated by detaching them from the index wheel 228 as a result of the pulling action of the wheel taking the cover sheet 230. It will be appreciated that once it is peeled off, the cover sheet 212 will be roll around the extraction wheel 230. In turn, the separate base sheet 210 is wound around the base sheet extraction wheel 232. A unit dose of Powdered catheter inside the blister-type open pocket 204 'is released in the opening station 238 and can be inhaled by the patient through the cavity of the duct 240 and ultimately through the nozzle 226. The exact shape of the duct that would be provided to the duct cavity 240 it is not visible in figure 2, but it will have a shape according to the present invention and as shown in the later figures herein. Figures 3a and 3b are highly schematic views of a second drug delivery device supported by the manually operated one 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 et al.), Whose entire content is incorporated herein by reference. That is, the second drug delivery device is provided with two medicament carriers 300a, 300b in the form of ampule-type flexible strips 302a, 302b described above with reference to Figure 1 (similar reference numbers are used to designate their characteristics) . The ampoule-type flexible strips 302a, 302b are identical, the pockets in each are of the same shape and size and are equi-separated along the length of the strip. A first strip 302a contains the same drug powder in each of its pockets, also with the same amount of active ingredients in each pocket of the strip. The other strip 302b similarly contains a medicament powder common in each of its pockets, each pocket again having the same amount of active ingredients therein. The drug powder in each strip may contain a single active ingredient or a mixture of active ingredients. Without However, the medicament powder in one strip contains at least one active ingredient different from that of the other strip. As will be further detailed below, in the operation of the second drug delivery device, a pocket of each ampule-type strip 302a, 302b is opened to expose the different medicament powders therein. The patient then inhales into the mouthpiece to simultaneously inhale the powders from the open pockets 304a, 304b of the strips 300a, 300b. The patient thus receives a fixed metered dose of the medicament powder whose different medicament powders from each of the open pockets 304a, 304b make up respective dose portions. Figure 3a illustrates a base unit 319 of the second drug delivery device. The first and second ampoule-type strips containing the drug 302a, 302b are placed within the respective left and right chambers 323a, 323b of the base unit 319. Each ampoule-type strip 302a, 302b is attached to a respective index wheel of multi-pocket 328a, 328b, and the successive pockets are thereby directed towards a commonly located opening station 333. The rotation of the index wheels 328a, 328b is engaged. In the opening station 333, the parts of the cover sheet 312a, 312b and the base sheet 310a, 310b of each strip 302a, 302b are detached over a respective peak 336a, 336b. The resulting empty base sheet 310a, 310b is wound into the respective extraction base chambers 332a, 332b. The used cover sheet 312a, 312b is fed on its respective peak 336a, 336b and wound on a cover removal spindle 330a, 330b in the cover extraction chamber 331a, 331b. The medicament released in powder form from the open pockets 304a, 304b of the first 302a and second strips 302b is accessible via a conduit 350, which is shown only schematically in Figure 3b, but which in this embodiment takes the form of one of the ducts 450, 550 shown in Figure 14a or Figure 16a and is described in detail with reference to the third drug delivery device of Figures 4 to 17. The duct 350 is located in the duct reception station 341. During the In use, the released powder travels from conduit 350 to a nozzle (not shown) in fluid communication therewith for inhalation of the patient. The conduit 350 defines a particular geometry through which the released powders travel to mix prior to delivery into the nozzle. The base unit 319 of Figure 3a allows different types of medication to be stored separately in each of the strips 302a, 302b but are released simultaneously and delivered to the patient as a multi-active "mixed" inhaled product. Figure 3b shows in more detail the release of the drug from the open pockets 304a, 304b (Figure 3a). The patient breathes through the mouthpiece (not shown) giving Resulting negative pressure that is transmitted through conduit 350 to open pockets 304a, 304b (FIG. 3a) of strips 302a, 302b in opening station 333. This commonly results in the creation of a venturi effect that results in to the dust contained within each of the open pockets 302a, 302b is removed through line 350 and thus to the mouthpiece for inhalation by the patient. Figures 4 to 15 provide several views of a third portable and manually operable drug delivery device in accordance with the present invention. The third drug delivery device is in the form of a dry powder inhaler and, as will be understood by the skilled reader, is similar in terms of its function and general principle of operation with respect to the second drug delivery device above. That is, the third drug delivery device is provided with two medicament carriers 400a400b in the form of blister-type flexible strip 402a, 402b, as described above with reference to Figure 1, with similar reference numbers which are used to indicate its characteristics. However, in the strips 402a, 402b the test pocket forms part of the equi-separated series of pockets 404a, 404b, instead of being further separated. The number of pockets 404a, 404b on each strip 402a, 402b is the same, the exact amount depends on how many days of treatment are thought and Dosing regimen As an example, the strips 402a, 402b would have 31 pockets each per day, 30 day treatment program. The additional pocket is the test pocket. The blister-type flexible strips 402a, 402b are identical, the pockets 404a, 404b in each are of the same shape and size and are equi-spaced along the length of the strip. The first of the strips 402a contains the same medicament powder in each of its pockets, also with the same amount of active ingredients in each pocket of the strip. The other strip 402b similarly contains a medicament powder common in each of its pockets, each pocket again having the same amount of active ingredients therein. The drug powder in each strip may contain a single active ingredient or a mixture of active ingredients. However, the medicament powder in one strip contains at least one active ingredient different from that of the other strip. As to what is further detailed herein below, when the device has been prepared for use and a patient inhales in a nozzle 426 of the device, the patient simultaneously inhales the single-walled open powder 404a, 404b of each strip 400a, 400b to receive a fixed metered dose of the medicament powder whose different medicament powders of each open pocket make up respective dose portions.

Figures 4a to 4c and figures 5a to 5c show corresponding sequential steps for preparing the third device distributor of medication for use. As shown, the third drug delivery device comprises a housing 420 provided with the nozzle 426 and a nozzle cover 438 for covering the nozzle 426. A window 424 is also provided to the remote 420 through which an indication of dose counting 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 duct 450 located in an opening station 427, the duct 450 is configured, in use, to direct the single-pocket drug powder opened from each strip 400a, 400b in the opening station 427 for inhalation by a patient. As can be seen in Figure 5a, the nozzle cover 438 has an arm 434 provided with a mounting opening 436 to be mounted for interaction with a ratchet 446 of a complex gear mechanism 440. During operation, the nozzle cover 438 rotatably moves about an axis defined by the rotatable axis of pawl 446. In Figures 4a and 5a, nozzle cover 438 is in a first position in which nozzle 426 is covered therein. In Figures 4b and 5b, the nozzle cover 438 has rotated to a second position, in which the nozzle 426 and a grate air inlet 470 are partially uncovered, but where the gear mechanism 440 and an associated dispensing mechanism, as described in more detail below, are not operated whereby no dose of medicament is available for inhalation. In addition, no actuation of the dose counter (not shown) has occurred whereby the count indication 425 remains the same. The count index 425 in this particular mode indicates the number of unopened pockets 404a, 404b located on each strip 402a, 402b. In Figures 4c and 5c, the nozzle cover 438 has further rotated to a third position to fully open or open the nozzle 426 and the air intake grill 470. The part of the cover 438 almost extends to the base 421 of the accommodation 420 in this position. As a result of the additional movement from the second to the third position of the gear mechanism (described in more detail with reference to figures 6 and 7a to 7c below), the dispensing mechanism (described in more detail with reference to Figure 9 below) has been operated on the dispensing device to make a dose of medicament available for inhalation. In other words, the drug dispensing device is now prepared for use. The movement has also resulted in the dropping of the dose counter (mechanism not visible) of the drug dispensing device such as to decrease the count indication 425 by one unit for a new one. reading "29". During subsequent use, the nozzle cover 438 is returned to the first position (ie as in Figures 4a and 5a). This corresponds to the storage position ("protected nozzle") of the distributor device. Referring now to Figure 6, aspects of the gear mechanism 440 are shown. In more detail, the housing 420 can be observed to be provided with an internal chassis 428 for external reception of the parts of the gear mechanism 440. Within the chassis 428 , and as best seen by reference to Figure 9, opposite distribution mechanisms 448a, 448b ("left" and "right") are provided for the drug distribution. It can be considered that the gear mechanism 440 forms part of the distribution mechanisms 448a, 448b. Referring to Figure 9 in more detail, the first and second medicament-containing blister-type strips 400a, 400b are placed within the respective left and right chambers 403a, 403b of the chassis 428. Each blister-type strip 400a, 400b is attached to the respective multi-pocket index wheel 430a, 430b, of the type used in the DISKUS® inhaler of GlaxoSmithKIine, as described and shown in US-A-2005/0126568 (Davies et al.) see Figure 16, wheel index 416 - and in the "twin strip" inhalation devices of US-A-2005/0154491 (Anderson et al.), and the successive pockets in this way they are directed towards a central opening station 427. In the opening station 427, the parts of the cover sheet 412a, 412b and the base sheet 410a, 410b of each strip 400a, 400b are detachably detached from each other. the peaks 409a, 409b. The resulting empty base sheet 410a, 410b is wound into the respective extraction base chambers 415a, 415b. The rotating base extraction 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 extraction base spindle 413a, 413b results in the "waste" base sheet 410a, 410b being 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 fed over its respective spout 409a, 409b and is wound onto the respective cover removal wheel 417a, 417b, which also rotates to wind the cover sheet 412a, 412b thereon. Each cover removal wheel 417a, 417b comprises a central axis, to which the ends 416a, 416b of the cover sheets 412a, 412b are respectively joined and on which they are wound, a central spindle (not shown) on which the axis rotates and in which a torsion spring (not visible) is mounted. This is described in detail in WO-A-2006/018261 (Glaxo Group Limited), particularly the modality in which it is described with reference to figures 1 to 4, whose International Application, together with the North American National Phase Patent Application derived therefrom, is incorporated herein by reference. The function of the torsion spring is to ensure that a very constant drive tension is provided to each strip 400a, 400b by its cover removal wheel 417a, 417b during the travel of each entire length of the strip. Particularly, each torsion spring acts to compensate for the variation of the drive tension associated with the increase in effective winding diameter of each cover removal wheel 417a, 417b while the used cover sheet 412a, 412b is gradually wound around the same Thus, the uniform indexing of each strip 400a, 400b can be maintained over the entire length of the strip. During use, the dispensing device is prepared as shown in Figures 4a to 4c and 5a to 5c by moving the cover 438 from the second position (as shown in Figures 4b and 5b) to the third position (according to FIG. shown in Figures 4c and 5c) for impulsively rotating index wheels 430a, 430b and cover removal wheels 417a, 417b to advance each blister-type strip 400a, 400b, thereby causing the main unopened pocket thereof to be releasably opened. To access the contents of the open pockets, the patient then breathes through the nozzle 426. As will be described in more detail with reference to figures 10 to 15, this gives place the negative pressure that is transmitted through a conduit 450 to the open pocket of each strip 400a, 400b in the opening station 427. This in turn results in the drug powder contained within each of the open pockets that they are extracted simultaneously through the common passage 450 to the nozzle 426 and therefore to the patient as an inhaled dose of the combination medicament. Referring again to Figure 6, the gear mechanism 440 can be considered to comprise the ratchet gear 442 mounted on the drive spindle 431. The ratchet gear 442, like the other gears, is of a wheel shape having faces opposite internal and external 441, 443 (in relation to the exterior of the distributor device) and an outer circumferential surface 445a therebetween. The outer face 443 is hollow to define an inner circumferential surface 445b in an opposite relationship to the outer circumferential surface 445a. As will be seen, the outer and inner circumferential surfaces 445a, 445b are provided with a stepped profile to give the respective external and internal ratchet characteristics 444a, 444b for progressive interaction with ratchet 446, whose interaction will be described in more detail with reference. to figures 7a to 7c. The features of 444a, 444b are equi-angularly spaced ratchet teeth; in this embodiment there are 5 teeth on each circumferential surface 445a, 445b. Teeth 444a in the outer circumferential surface 445a ("outer teeth 444a") are offset from teeth 444b on inner circumferential surface 445b ("internal teeth 444b"). That is, none of the internal teeth 444b are located in the same radius of the axis of rotation of the gear 442 as the external teeth 444a. As will be seen from Figure 7a, the inner circumferential surface 445b comprises the surface segments 449 that connect each adjacent pair of internal teeth 444b. Each surface segment 449 consists of first and second sections 449a, 449b that extend internally from opposite ends of segment 449, first section 449a extends internally to second section 449b from an internal tooth 444b and the second section 449b extends internally to the first section 449a from the next adjacent internal tooth 444b. The radius of curvature of the first section 449a is greater than that of 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 spindles 413a, 413b and the base removal spindles (not shown) of the cover removal wheels 417a, 417b are respectively connected to the base removal gears 462a, 462b and with the cover removal gears 5 461a, 461b. The index wheels 430a, 430b are also provided with the gears. The inner face 441 of the ratchet gear 442 is provided with the driving gear teeth 447 for the drive interaction (coupling) with (i) the gear of the first index wheel 430a, and with (i) a first gear inactive 464. The gear of the first index wheel 430a engages with the first of the cover removal wheel gears 461a and with the gear of the second index wheel 430b, which in turn engages with the second gear of cover extraction 461b. The first idle gear 464 is coupled with the first of the base extraction spindle gears 462b and with a second idle gear 465, which in turn engages with the second base extraction spindle gear 462a. This gear train arrangement provides indexation of the medicament carriers 400a, 400b and winds the base and cover sheet sheets 410a, b, 412a, b during movement of the nozzle cover 438 from its second position to its third position. A more detailed description of a convenient counter mechanism for use in the distributor device is provided in WO-A-2005/079727 (Glaxo Group Limited) which, together with the US National Patent Application No. 10 / 597,551 derived from it is incorporated herein by reference. The base extraction spindle 413b can be used to drive this mechanism opposite by the coupling with the driving wheel / wheel of lifting gear thereof. As shown in Figures 6 to 8, the pawl 446 comprises a central axis 446a of the outer circumference which depends on a plurality of circumferentially oriented elastic legs in an equi-angular manner 446b. The ratchet shaft 446a further comprises a boss 446c which, as shown in Fig. 5a, fits into the mounting opening 436 of the nozzle cover arm 434 to establish a direct drive connection between the nozzle cover 438 and the ratchet 446 whereby the rotational movement of the nozzle cover 438 between its first to the third position causes the rotational movement of the pawl 446 in the ratchet gear 442, as will be described in more detail below. In this particular modality, 5 ratchet legs 446b depend on the ratchet shaft 446a. That is, the number of ratchet legs 446b is chosen to equal the number of internal teeth 444b of the ratchet gear 442. The interaction of the ratchet gear 442 with the ratchet 446 can be better understood with reference to FIGS. 7a to 7c, which show the movement of the parts of the gear mechanism 440 of the third drug delivery device when it is ready for use in the sequential steps corresponding to those of Figures 4a to 4c. In the immobility position of figure 7a (ie the nozzle cover 438 closed), ratchet 446 is angularly located in ratchet gear 442 to circumferentially separate the inner teeth 444b of the ratchet gear 442 from the free ends of the ratchet legs 446b. In the second position of Fig. 7b (ie the nozzle cover 438 partially open), the ratchet 446 has rotated about in the ratchet gear 442 to slide the ratchet legs 446b onto the adjacent surface segments 449 of the circumferential surface. internal 445b for coupling the internal teeth 444b. It will therefore be appreciated that in this second position, the ratchet gear 442 is ready for movement but still does not move, and therefore that the entire gear mechanism 440 and the dispensing mechanisms 448a, 448b have not advanced. In the third position of Fig. 7c (i.e. nozzle cover 438 fully open), ratchet 446 and ratchet gear 442 rotate together (72 ° as shown) through inter-engagement of ratchet legs 446b and of the internal teeth 444b such as to advance the entire gear mechanism 440 and the dispensing mechanisms 448a, 448b such as to index and advance each medicament carrier 400a, 400b to open a single pocket of each and such way to make the medicament powder contained in each open pocket available in line 450 at opening station 427 for simultaneous inhalation by the patient through the open nozzle 426. Referring to Figure 8, the dispensing device further comprises an internal retaining plate 481 for covering the gear mechanism 440. The retainer plate 481 is provided with an arched platform 483 which is located on the ratchet gear 442 and the pawl 446. One end of the platform 483 is configured while an elastic finger 484 on which a notch 485 is provided. The pawl 446 includes a projection 446d which engages the notch when the pawl (and thus both the nozzle cover 438) is in its first immobility position of figure 7a, as shown in figure 8. This inter-engagement of the ratchet protrusion 446d and the notch of retaining plate 485 acts as a brake for notching the nozzle cover 438 in the "closed nozzle" or in the immobile position of figures 4a, 5a, 7a and 8. The retaining plate 481 still further comprises a fixed elastic trigger leg 487 for interaction with the outer teeth 444a of the ratchet gear 442 to form an "anti-return" feature for the ratchet gear 442. When the nozzle cover 438 is opened, causing the ratchet 446 to rotate and after the ratchet gear 442 once the ratchet legs 446b engage the internal teeth 444b, the trigger leg 487 is not an impediment to the rotational movement of the ratchet gear 442 while the trigger leg 487 travels over the external teeth 444a due to its orientation and the elasticity of the trigger leg 487. However, when the nozzle cover 438 returns to its closed position, in turn rotates the pawl 446 back to its immobile position, the ratchet gear 442 is held against the return turn by the engagement of the trigger leg 487 with one of the outer teeth 444a. Accordingly, the reverse rotation of the pawl 446 upon closing the nozzle cover 438 is not transmitted to the gear mechanism 440. Thus, on each occasion the nozzle cover 438 is fully opened and closed, the ratchet gear 442 is increased by only a rotating direction. When the nozzle cover 438 returns to its first cover position (FIG. 4a) to rotate the pawl 446 in the gear 442 back to its immobile position (FIG. 7a), the spring legs 446b slide again onto the inner circumferential surface 445b to be separated behind different internal teeth 444b ready for the next opening of the nozzle cover 438. In figure 7a an enlarged view is shown to one of the gear teeth of the index wheel 430a showing the profile thereof . The gear teeth of all the gears in the gear mechanism are provided with this profile. Briefly, the manual movement, by the patient, of the nozzle cover 438 of its first position, in which closes the nozzle 426 (for example figure 4a), to its third position, in which the nozzle 426 is completely opened (for example figure 4c), gives rise to the ratchet 446 that drives the gear and the distribution mechanisms 440, 448a, 448b for indexing each blister-type strip 402a, 402b in the dispensing device to cause a single ampule-type pocket 404a, 404b of each strip 402a, 402b to open and present for duct 450 at opening station 427 ready for The patient simultaneously inhales the powder content of each newly opened pocket 404a, 404b and thus receives a fixed dose of a combination of different drug actives. After the patient has inhaled the powder content of each newly opened pocket, the patient manually returns the nozzle cover 438 to its first position ready for the next use. During the next use, the next closed pocket 404a, 404b on each strip 402a, 402b will be opened and indexed in line 450 to allow the patient to inhale the next fixed dose of drug combination. This closing and opening cycle then continues, in accordance with the prescribed regimen for drug combination (for example once a day, twice a day, etc.), until all pockets 404a, 404b, are empty, as it will be. as evidenced by the count index 425. As described above, the movement of the nozzle cover 438 from its first position to the second intermediate position (e.g. figure 4b) does not result in the indexing / opening of blister-type pockets 404a, 404b. A more detailed description of the duct 450 of the third drug delivery device now continues with reference to Figures 10 to 15. Figure 10 shows a third drug delivery device without its nozzle 426. In more detail, the cover 420 comprises coupling the first 420a and the second parts of the housing cover 420b, which in the combination acts to contain the mechanisms of the distributor device thereof. The conduit 450 is received by the first housing cover part 420a such that a flange defining an inlet 453 in a chimney 452 is received within an inner wall 472 of the first housing part 420a defining the entrance grate of air 470. As described above, and as shown in Figures 4a to 4c, the air intake grill 470 in the first housing cover part 420a is covered by the nozzle cover 438 when in its first position or closed position (figure 4a), is partially uncovered when the nozzle cover 438 is in its second or semi-open position (FIG. 4b) and is fully revealed when the nozzle cover 438 is in its third open position or position (FIG. 4c). During use, the air inlet grill 470 allows the air to pass from the outside of the third distributor device of medication to conduit 450 via chimney inlet 453 to chimney 452 in response to patient inhalation through nozzle 426, as indicated schematically by arrow 483 in Figure 12. Notably, this air intake grill 470 provides the only intended point of entry of outside air into the medicament dispensing device during inhalation of the patient in the nozzle 426. More particularly, the air inlet grate 470 provides the single point of air entry out of the dispensing device for passing into conduit 450 during inhalation of the patient in nozzle 426. Conduit 450 is also received by the second housing cover part 420b such that its projecting leg 455 is seated within the conduit receiving cavity 475 thereof. The conduit 450 is provided with a pair of wings 456a, 456b which are mounting features that allow the conduit 450 to be pushed over the nozzle 426. As can also be observed by reference to FIGS. 12 to 15, the conduit 450 has a structure particular internal in which the chimney 452 is located on a chamber 460 and partially shares a common wall 459 therewith, the common wall 459 forms the lower wall of the chimney 452 and the part of the upper wall of the chamber 460. terms "on", "inferior" and "superior" are used only to describe the relative location of the characteristics in the duct 450 in the orientation in which duct 450 is shown in Figures 12 and 13. Chimney 452 has chimney inlet 453 and a pair of chimney outlets 454a, 454b. During use, the chimney 452 directs the internal air flow (while it is received exclusively through the air inlet grill 470 during patient inhalation at the nozzle 426) of the chimney inlet 453 to the output pairs of chimney 454a, 454b. The camera 460 has a pair of camera inputs 473a, 473b and camera outputs 474. The pair of chimney outputs 454a, 454b and the pair of camera inputs 473a, 473b are defined by a pair of circular holes, in this case. particular mode of a diameter of about 3 mm, and each hole is provided with a respective cross shape 451, 461. Each chimney outlet 454a, 454b forms a pair with one of the chamber inlets 473a, 473b by placing them adjacently between yes. The nozzle 426 is provided in the chamber outlet 474 and is press-fitted thereto via the pressure mounting fitting 476. As detailed above, when the nozzle cover 438 is fully opened in its third position, the gear and the dispensing mechanisms 440, 448a, 448b are operated to cause each strip 400a, 400b to advance and a single blister-type pocket 404a, 404b of each strip to be releasably opened. As will be understood from FIGS. 14b and 15c, the open blister-type removable pocket 404a, 404b of each strip 400a, 400b is located adjacent to the pairs of chimney outlets 454a, 454b and chamber inlets 473a, 473b. Specifically, the blister-type open pocket 404a of the first blister-type strip 402a is located adjacent to the first chimney outlet 454a and the first chamber inlet 473a (as shown in Figure 15c) and the blister-type open pocket. 404b of the second blister type strip 402b is also located adjacent to the other chimney outlet 454b and camera input 473b. As previously described with reference to Figure 1, the type pockets 404a, 404b are elongated, which extend laterally relative to the longitudinal axis of the strip 402a, 402b. The pockets 404a, 404b can therefore be considered to have first and second sides on opposite sides of the longitudinal axis of the strip. When open pockets 404a, 404b are presented in conduit 450 at opening station 427, the pockets 404a, 404b are oriented to align the lateral orientation thereof with the direction between the respective chimney outlets 454a, b and chamber inlets 473a, b. Thus, as shown in Figure 15c, the chimney outlet 454a, b and the chamber outlets 473a, 473b are located on the different sides of the pockets 404a, 404b, whereby, during use, the air passes through the pockets 404a, 404b in the oblique orientation thereof; that is, laterally in relation to the longitudinal axis (or to the length direction) of the strip 402a, 402b. As shown in Figures 12, 13 and 15, when a patient inhales in the nozzle 426, an air stream 483 flows out of the distributor device in the duct 450 only through the air intake grill 470 in the chimney 452 via the chimney inlet 453, which is in a juxtaposed relationship with the air intake grill 470. As graphically depicted in Figures 13, 15a and 15c, the first (or primary) portions 485 of this air stream 483 flow into the blister-type open pocket 404a, 404b of each strip 400a, 400b at the opening station 427 via the respective chimney outlet 454a, 454b, thereby suspending medicament powder contained in the pockets in the air stream, and so both outside the pockets 404a, 404b in the chamber 460 via the camera inputs 473a, 473b. The air stream with the suspended medicament powder then flows out of the nozzle 426 into the patient's airway. As shown in Figures 12 to 15, a single D-shaped discharge hole 480 is provided to the wall 459 that separates the chimney 452 from the chamber 460. The D-shaped discharge orifice 480 is located adjacently. to both chimney outlets 454a, 454b and chamber inlets 473a, 473b. As depicted graphically in Figures 13, 15b and 15c, during use, the discharge orifice 480 acts by example for directing a second portion 486 of the air stream 483 (the "suspension portion") of the chimney 452 directly to the chamber 460 to detrimentally affect the first portions 485 of the air stream 483 transporting the medicament powder suspended in the chamber 460 and thereby separate any agglomerated powder component therefrom. It should be noted that Figures 15a and 15b show only selectively the flow paths of the first 485 and second 486 portions of the air stream 483 to facilitate illustration. As the skilled artisan will appreciate, the first and second portions 485, 486 are concurrently created in conduit 450 during patient inhalation in mouthpiece 426, as indicated in Figures 13 and 15c. Figures 16 and 17 show a second duct 550 for the third drug delivery device which is a variation (and alternative) of the duct 450 with a discharge orifice of the "D-shaped orifice" type 480. Those characteristics in the second duct 550 which correspond to the characteristics in the first conduit 450 are designated with similar reference numerals. It will be appreciated that the profile and the overall shape of this second duct 550 correspond to those of the "D-shaped hole" type duct 450 such that it can be easily replaced by another in the third medication dispensing device. However, instead of the "D-shaped hole" type discharge port 480, the second conduit 550 has two elongated slit-shaped discharge ports 580a, 580b provided to the wall 559, which separates the chimney 552 from the chamber 560. In more detail, the second conduit 550 has an internal structure in which the chimney 552 is located on the chamber 560 and partly shares a wall 559 with it, the wall 559 forms the lower wall of the chimney 552 and the part of the upper wall of the chamber 560. The terms "on", "lower" and "upper" are used only to describe the relative location of the features in the duct 550 in the orientation in which the duct 550 is shown in Figure 17a. The wings 556a, 556b are provided to the conduit as before. The chimney 552 has a chimney inlet 553 and dual chimney outlets 554a, 554b. In use, the chimney 552 directs the internal air flow 583 (again, as received exclusively through the air inlet grill 470 as shown in figure 17a) from the chimney entrance 553 to the chimney outlets 554a, 554b. The camera 560 has dual chamber inputs 573a, 573b and one chamber outlet 564. The chimney outlets 554a, 554b and chamber inlets 573a, 573b, both are defined by the circular holes of diameter of approximately 3 mm, and each one 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 adjacent to each other such that when an open pocket Ampoule type 404a, 404b (see Figs. 16b and 17a) is located adjacent to the same adjacent ones in an opening station 427 (e.g. Fig. 11), the first portions 585 of the internal air flow 583 are directed via the open pockets 404a, 404b of the chimney outlets 554a, 554b to the chamber inlets 573a, 573b and to the chamber 560. This airflow in the blister-type open pocket 404a, 404b suspends the powder content of the respective pockets 404a, 404b and allows the transport thereof in the inhalation air flow 583 of the chamber inlets 573a, 573b to the chamber outlet 564, and therefore for the inhalation of the patient via the nozzle 426. The orifice Slot-shaped elongated discharge ports 580a, 580b are provided to wall 559, which separates chimney 552 from chamber 560. Slot-shaped elongated discharge ports 580a, 580b are located distally from both chimney outlets 554a, 554b and camera inputs 573a, 573b. As depicted graphically in Figures 17a and 17c, during use, discharge orifices 580a, 580b act such as to direct the second portions 586 of the flow air 583 ("unloading portions") of chimney 552 directly to chamber 560 to adversely affect the first portions 585 of airflow 583 that transport the suspended medicament powder and thereby separate any agglomerated component from the powder of the same. Referring to Figure 16a, each discharge orifice 580a, 580b has a width at its first end very close to the chamber outlet 574 of 1.32 mm (± 0.15 mm), a width at the second opposite end very close to the exit of the chamber. chimney 554a, 554b of 1.11 mm (± 0.15 mm), and a length of the first end to the second end of 6.465 mm (± 0.1 mm). The cross-sectional area of each discharge orifice 580a, 580b is 7.8 mm2. The discharge ports 580a, 580b therefore have a taper profile, which narrows from the first end to the second end. Of course, these dimensions can be changed depending on the drugs that will be supplied from the ampule-type strips 402a, 402b. As will be appreciated, the first and second portions 585, 586 of the air stream 583 occur concurrently in the duct 550 as a result of inhaling the patient in the nozzle 426. As will also be seen from FIG. discharge 580a, 580b are configured and located so that the second portions 586 of air stream 583 flow additionally around the boundary surface 591 of the chamber 560, forming an envelope-type air cover adjacent to the boundary surface 591. This helps alleviate the deposition of medicament powder on the boundary surface 591 while the powder is brought to the nozzle 426. It will be noted that the internal structure of the conduits 450, 550 is such that the longitudinal axis of the chimney 452; 552, which extends 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 extends from the chamber inlets 473a, b, 573a , at the chamber outlet 474, 574. Thus, the discharge portions 486; 586 of the inhalation air stream 483, 583 first affect the portions carrying the medicament 485, 585 in the chamber 460, 560 at right angles thereto or generally at right angles thereto. It will also be noted that the ducts 450; 550 require all air flow in the conduit via the chimney inlet 453; 553, for example that then acts to "separate" the total air flow 483; 583 in the "directed" open air ampoule portion 485; 585 (via chimney exits 454a, b; 554a, b and chamber inlets 473a, b; 573a, b) and a "discharge" air portion 486; 586 (via one or more discharge ports 480; 580a, b) to chamber 460; 560. Good control over the amount of discharge air 486; 586 and, particularly, the percentage of it (in relation to the flow of total air entering duct 450; 550 via the chimney entrance 453; 553) is therefore possible with a conduit having this configuration. For the third drug delivery device, which has a pair of medicament carriers 400a, 400b, the discharge air portion 486; 586 of the total air flow 483; 583 is ideally 80%, or substantially 80%, the balance passes through the open pockets 404a, 404b. It will be appreciated that there will probably be some leakage of air in the conduits 450; 550 during inhalation of the patient in the nozzle 426, particularly via the chimney outlets 454a, b; 554a, b and, perhaps more particularly, via the chimney entries 473a, b; 573a, b, since blister-type strips 402a, 402b will not form a complete seal fit over these openings in conduit 450; 550. However, any leakage of air is negligible compared to the expected total inhalation air flow 483; 583 extracted in line 450; 550 through the chimney entrance 453; 553 via the air inlet grill 470. In the modes described above, the ducts 450; 550 are plastic components molded by injection in one piece. More particularly, the conduits 450; 550 are made of high density polyethylene (HDPE), since this material is suitable for the injection molding of duct 450; 550, particularly high injection molding speed, while having a surface energy sufficiently low to minimize or inhibit the deposition of drug powder therein. However, other materials and manufacturing or molding processes could be used. Since other possible materials can be mentioned fluoropolymers, for example fluorinated ethylene-propylene (FEP), and other non-fluoropolymers, for example polypropylene (PP). It can be appreciated that any part of the device or any component thereof that comes into contact with the medicament can be comprised of or coated with materials such as fluoropolymer materials (e.g. PTFE or FEP) that reduce the tendency of the medicament to adhere the same. Any movable part may also have coatings applied thereto that improve its desired movement characteristics. Frictional coatings can therefore be applied to improve frictional contact and lubricants (eg silicone oil) used to reduce frictional contact as necessary. In particular, the duct itself may be completely or partially comprised of or coated alternatively partially or completely with materials that reduce the tendency of the drug to adhere thereto. Such materials can, for example, decrease the surface energy of the relevant duct surface.

Conveniently, fluoropolymer materials are used. High density polyethylene (HDPE) and / or modified acetal materials are also convenient. Suitable fluoropolymer materials include those comprising multiples of one or more of the following monomer units: tetrafluoroethylene (PTFE), fluorinated ethylene propylene, perfluoroalkoxyalkane (PFA), ethylene tetrafluoroethylene (ETFE), vinylidene fluoride (PVDF), and ethylene tetrafluoroethylene chlorinated Fluorinated polymers, which have a relatively high ratio of fluorine to carbon, such as perfluorocarbon polymers, for example, PTFE, PFA and FEP are particularly convenient. Particularly when used as coatings, the fluoropolymer is optionally mixed with a non-fluorinated polymer such as polyamides, polyimides, polyamide imides, polyethersulfones, polyphenylene sulfides, and thermoset amine-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 further be appreciated that the "brief description of the invention" section describes additional details, modifications or adaptations of the examples of drug dispensing devices, medicament carriers and conduits described with reference to the appended figures.

Where not indicated, the components of the drug dispensing devices herein can be manufactured from conventionally designed materials, especially conventionally designed plastic materials, more especially those that allow the molding of the component. The conduit herein is suitable for use in a medicament dispensing device for dispensing the powdered formulations of medicament, particularly for the treatment of respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD), bronchitis and chest infections. Particularly, the conduit can be used in the delivery of a drug powder formulation based on one or more of the drugs listed below. Where the conduit is used with only a single blister-type package, the formulation of medicament in the package may comprise only one of the listed drugs (a monotherapy) or a plurality of listed drugs (combination therapy). Where the conduit for use with plural blister packs (particularly two), each pack may contain a medicament powder formulation comprising one or more of the listed drugs, a packet containing at least one medicament not found in, or at least one of another package. Where the conduit for is for use with two blister-type packages, the formulation of Drug powder in a package comprises a medicament not found in the other package. Commonly, each package will have different medications than the other package. 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 as sodium salt), cetotifen or nedocromil (for example as sodium salt); anti-infectives for example; cephalosporins, penicillins, streptomycin, sulfonamides, tetracyclines and pentamidine; antihistamines, for example, metapyrylene; anti-inflammatories, for example beclomethasone (for example as dipropionate ester), fluticasone (for example as propionate ester), flunisolide, budesonide, rofleponide, mometasone (for example as furoate ester), ciclesonide, triamcinolone (for example as acetonide) or ester (2-oxo-tetrahydro-furan-3-yl) of 6a, 9a-difluoro-11β-hydroxy-16a-methyl-3-oxo-17a-propionyloxy-androsta-1,4-dienic acid 17ß-carbothioic; antitussives, for example, noscapine; bronchodilators, for example, albuterol (for example as a free base or sulfate), salmeterol (for example as a xinafoate), ephedrine, adrenaline, fenoterol (for example as a hydrobromide), salmefamol, carbuterol, mabuterol, etanterol, naminterol, clenbuterol, flerbuterol, bambuterol, indacaterol, formoterol (for example as fumarate), isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (for example example as acetate), reproterol (for example as hydrochloride), rimiterol, terbutaline (for example as sulfate), isoetarin, tulobuterol or 4-hydroxy-7- [2 - [[2 - [[3- (2-phenylethoxy) propyl] ] sulfonyl] ethyl] amino] ethyl-2 (3H) -benzothiazolone: adenosine 2a agonists, for example (2R, 3R, 4S, 5R) -2- [6-amino-2- (1S-hydroxymethyl-2-phenyl -ethylamino) -purin-9-yl] -5- (2-ethyl-2H-tetrazol-5-yl) -tetrahydro-furan-3,4-diol (for example as maleate); inhibitors of integrin a4 for example (2S) -3- [4- ( { [4- (aminocarbonyl) -1-piperidinyl] carbonyl} oxy) phenyl] -2 - [((2S) -4- methyl-2- { [2- (2-methylphenoxy) acetyl] amino.} pentanoyl) amino] propanoic (for example as free acid or potassium salt), diuretic, eg, amiloride; anticholinergics, for example, ipratropium (for example as bromide), tiotropium, atropine or oxitropium; hormones, for example, cortisone, hydrocortisone or prednisolone; xanthines, for example, aminophylline, choline theophyllinate, usin theophyllinate or theophylline; proteins and therapeutic peptides, for example, insulin or glucagon; vaccines, diagnostics, and genetic therapies. It will be clear to one skilled in the art that, when appropriate, the medicaments may be used in the form of salts, (for example, as alkali metal or amine salts or as acid addition salts) or as esters (e.g. lower alkyl esters) or as solvates (eg, hydrates) to optimize the activity and / or stability of the medicament. The product of the formulated medication can in aspects, be a monotherapy product (that is, a single product that contains the active drug) or it can be a combination therapy product (ie it contains plural active drugs). Suitable medicaments or drug components of a combination therapy product are commonly selected from the group consisting of anti-inflammatory agents (e.g., a corticosteroid or NSAID), anticholinergic agents (e.g., an M, M2 receptor antagonist, Mt / M2 or M3), other ß2 adrenoreceptor agonists, anti-infective agents (for example an antibiotic or antiviral), and antihistamines. All are considered convenient combinations. Suitable antiinflammatory agents include corticosteroids and NSAIDs. 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 6a, 9a-di fluoro-17a - [(2-fura nylcarbonyl) oxy] -11β-hydroxy-16a-met il-3- oxo-androsta-1,4-dien-17β-carbothioic, S- (2-oxo-tetrahydrofura n-3S-yl) ester of 6a, 9a-difluoro-11β-hydroxy-16a-methyl-3 -oxo-17a-propionyloxy-androsta-1,4-dien-17β-carbothioic acid, esters of beclomethasone (for example ester of 17-propionate or ester of 17,21-dipropionate), budesonide, flunisolide, esters of mometasone (for example furoate ester), triamcinolone acetonide, rofleponide, ciclesonide, butyxocort propionate, RPR-106541, and ST-126. Preferred corticosteroids include fluticasone propionate, S-fluoromethyl ester of 6a, 9a-di-fluoro-11-hydroxy-16a-methyl-17a - [(4-methyl-1,3-thiazole-5-carbonyl) oxy] - 3-oxo-androsta-1,4-dien-17β-carbothioic acid, S-fluoromethyl ester of 6a, 9a-difluoro-17a - [(2-furanylcarbonyl) oxy] -11β-hydroxy-16a-methyl-3-oxo- androsta-1,4-dione-17β-carbothioic acid, S-cyanomethyl ester of 6a, 9a-difluoro-11β-h id roxi-16a-met i-3-oxo-17a- (2, 2,3 , 3-tetramethoxypropylcarbonyl) oxy-androsta-1,4-diene-17β-carbothioic acid, S-fluoromethyl ester of 6a, 9a-difluoro-11β-hydroxy-16a-methyl-17a- (1-meticyclopropylcarbonyl) oxy- 3-oxo-androsta-1,4-diene-17β-carbothioic acid and 9a, 21-dichloro-11β, 17a-methyl-1,4-pregnadiene-3,20-dione-17- [2 '] furoate (furoate of mometasone). Additional corticosteroids are described in WO02 / 088167, WO02 / 100879, WO02 / 12265, WO02 / 12266, WO05 / 005451, WO05 / 005452, WO06 / 072599 and WO06 / 072600. Non-spheroidal compounds having glucocorticoid agonism which may possess the selectivity for transrepression during transactivation and which may be useful in combination therapy through the conduit herein 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 NSAIDs 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 inhibitors and elastase, beta-2 integrin antagonists and adenosine receptor agonists or antagonists (e.g., adenosine agonists 2a), cytokine antagonists (e.g. chemokine antagonists), cytokine synthesis inhibitors or 5-lipoxygenase inhibitors. 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. Suitable bronchodilators are β2 adrenoreceptor agonists, including salmeterol (which may be a racemate or a single enantiomer, such as R-enantiomer), for example salmeterol xinafoate, salbutamol (which may be a racemate or a single enantiomer, such as R-enantiomer). ), for example salbutamol sulphate or as the free base, formoterol (which may be a racemate or a single diastereomer, such as an R, R-diastereomer), for example formoterol fumarate or terbutaline and salts thereof. Other suitable β 2 -adrenoceptor agonists are 3- (4-. {[[6- ( { (2R) -2-hydroxy-2- [4-hydroxy-3- (hydroxymethyl) phenyl] ethyl} amino) hexyl] oxy] butyl) benzenesulfonamide, 3- (3. {[[((({(2 (R) -2-hydroxy-2- [4-hydroxy-3-hydroxymethyl) phenyl] ethyl]} -amino) heptyl] oxy} propyl) benzenesulfonamide, 4-. { (1R) -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-hydroxy-5 - [(1 R) -1-hydroxy-2 - [[2-4 - [[(2R) -2-hydroxy-2-phenylethyl ] amino] phenyl] ethyl] amino] etl] phenyl] formamide, and N-2. { 2- [4- (3-phenyl-4-methoxyphenyl) aminophenyl] ethyl} -2-hydroxy-2- (8-hydroxy-2 (1H) -quinolinon-5-yl) ethylamine, and 5 - [(R) -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 approximately 12 hours or more. Other ß2 adrenoreceptor agonists include those described in WO 02/066422, WO02 / 070490, WO02 / 076933, WO03 / 024439, WO03 / 072539, WO03 / 091204, WO04 / 016578, WO2004 / 022547, WO2004 / 037807, WO2004 / 037773, WO2004 / 037768, WO2004 / 039762, WO2004 / 039766, WO01 / 42193 and WO03 / 042160. Suitable phosphodiesterase 4 (PDE4) inhibitors include compounds that are known to inhibit the PDE4 enzyme or that are discovered 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 a Cl50 ratio of about 0.1 or greater with respect to Cl50 for the catalytic form of PDE4 that binds rolipram with a high affinity divided by Cl50 for the form that binds to rolipram with a low affinity. For purposes of this disclosure, the cAMP catalytic site that binds to rolipram R and S with a low affinity is termed the "low affinity" binding site (LPDE 4) and the other form of this catalytic site that binds to rolipram with high affinity is termed as the "high affinity" binding site (HPDE 4). This term "HPDE4" should not be confused with the term "hPDE4" which is used to denote the Human PDE4 A method for determining the Cl50s ratios is set forth in U.S. Patent No. 5,998,428 which is incorporated herein by reference in its entirety as if it were found herein. See also the PCT Application WO00 / 51599 for another description of the analysis. Suitable PDE4 inhibitors include compounds that have a healthy therapeutic relationship, i.e., compounds that preferentially inhibit the catalytic activity of cAMP where the enzyme is in the form that binds rolipram with a low affinity, thereby reducing the side effects that are apparently linked to the inhibition of the form that binds rolipram with a high affinity. Another way of indicating this is that the preferred compounds have a Cl50 ratio of about 0.1 or greater as far as Cl50 is concerned for the catalytic form of PDE4 that binds rolipram with a high affinity divided by Cl50 for the form that binds to rolipram with a low affinity. Another modification of this standard is that of one in which the PDE4 inhibitor has a Cl50 ratio of about 0.1 or greater; the ratio is the ratio of the Cl50 value to compete with the binding of 1 nM of [3H] R-rolipram to a form of PDE4 that binds rolipram with a high affinity to the Cl50 value to inhibit the catalytic activity of PDE4 from a form that binds rolipram with a low affinity using 1 μM [3 H] -cAMP as the substrate. The most convenient are PDE4 inhibitors that have a Cl50 ratio greater than 0.5, and particularly those compounds that have a ratio greater than 1.0. Preferred compounds are c / 's-4-cyano-4- (3-cyclopentyloxy-4-methoxyphenyl) cyclohexane-1-carboxylic acid, 2-carbomethoxy-4-cyano-4- (3-cyclopropylmethoxy) 4-difluoromethoxyphenyl) cyclohexan-1 -one and c / s- [4-cyano-4- (3-cyclopropylmethoxy-4-d, fluoro-methoxy-phenyl) cyclohexan-1-ol]; these are examples of the compounds that preferably bind to the low affinity binding site and have a Cl50 ratio of 0.1 or higher. Other suitable drug compounds include: c / s-4-cyano-4- [3- (cyclopentyloxy) -4-methoxyphenyl] cyclohexane-1-carboxylic acid (also known as cilomalast) described in U.S. Patent No. 5,552,438 and its salts, esters, prodrugs or physical forms; AWD-12-281 by elbion (Hofgen, N. et al 15th EFMC Int Symp Med Chem (Sept. 6-10 Edinburgh) 1998, Abst P.98; CAS reference No. 247584020-9); a 9-benzyladenine 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-11294A 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 (CAS reference No. 162401-32-3) and ptalazinone (WO99 / 47505, the disclosure of which is incorporated herein by reference) by Byk-Guilden; Pumafentrine, (-) - p [(4aR *, 10bS *) - 9-ethoxy-1,2,3,4,4a, 10b-hexahydro-8-methoxy-2-methylbenzo [c] [1,6] naphthyridin -6-yl] -N, N-diisopropylbenzamide which is a PDE3 / PDE4 mixed inhibitor which has been prepared and published by Byk-Gulden, now Altana; arophylline under the development of 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 the compounds that act as antagonists at the muscarinic receptor, particularly the compounds, which are antagonists of the M or M3 receptors, dual antagonists of M? / M3 or M2 / M3, receptors or pan-antagonists of the receptors M? / M2 / M3. Exemplary compounds include the alkaloids of the belladonna plant as illustrated by the like of atropine, scopolamine, homatropine, hyoscyamine; These compounds are normally administered as salt, which are tertiary amines. Other suitable anti-cholinergic agents are muscarinic antagonists, for example (3-epdo) -3- (2,2-di-2-thienylethenyl) -8,8-dimethyl-8-azoniabicyclo [3.2.1] octane iodide, (3-e /? do) -3- (2-cyano-2,2-diphenylethyl) -8,8-di-ethyl-8-azoniabicyclo [3.2.1] octane bromide, 4- [hydroxy (diphenyl ) methyl] -1-. { 2 - [(phenylmethyl) oxy] ethyl} -1-azonia-bicyclo [2.2.2] octane, (1 R, 5S) -3- (2-cyano-2, 2-d-phen-methylene) -8-methyl-8-bromide -. { 2 - [(phenylmethyl) oxy] ethyl} -8-azoniabicyclo [3.2.1] octane, (eA? UO) -3- (2-methoxy-2,2-d, thiophene-2-yl-ethyl) -8,8-dimethyl-8-iodide -azonia-bicyclo [3.2.1] octane, (endo) -3- (2-cyano-2,2-diphenyl-ethyl) -8,8-dimethyl-8-azonia-bicyclo [3.2.1] iodide ] octane, iodide (endo) -3- (2-carbamoyl-2,2-diphenyl-ethyl) -8,3-dimethyl-8-azonia-bicyclo [3.2.1] octane, iodide (enc / o) -3- (2-cyano-2,2-di-thiophen-2-yl-ethyl) -8,8-dimethyl-8-azonia-bicyclo [3.2.1] octane, and bromide of (enoO) -3-. { 2,2-Diphenyl-3 - [(1-phenyl-methanoyl) -amino] -propyl} -8,8-dimethyl-8-azonia-bicyclo [3.2.1] octane. Particularly convenient anticholinergics include ipratropium (for example as bromide), sold under the name Atrovent, oxitropium (for example as bromide) and tiotropium (for example as bromide) (CAS-139404-48-1). Also of interest are: metantelin (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), copyrrolate (Robinul), iopropamide iodide (CAS-71-81-8), mepenzolate bromide (U.S. Patent No. 2,918,408), tridihexetyl chloride (Pathilone, CAS-4310 -35-4), and hexocrylic metiisulfate (Tral, CAS-115-63-9). See also 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 (eg, as hydrobromide, CAS 262586-79-8) and LAS-34273 which is described in WO01 / 04118, darifenacine (CAS 133099-04-4, or CAS 133099-07-7 for the hydrobromide sold under the name Enablex), oxybutynin (CAS 5633-20-5, sold under the name Ditropan), terodiline (CAS 15793-40-5), tolterodine (CAS 124937-51-5, or CAS 124937-52-6 for the tartrate, sold under the name Detrol), otilonium (for example, as 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 name Vesicare). Other anticholinergic agents include the compounds described in USSN 60 / 487,981 and USSN 60 / 511,009. Suitable antihistamines (also referred to as HT receptor antagonists) include any of one or more of the numerous known antagonists that inhibit H-i receptors, and are safe for human use. All are reversible and competitive inhibitors of the interaction of histamine with H ^ receptors. Examples include ethanolamines, ethylenediamines, and alkylamines. In addition, other first generation antihistamines include those that can be characterized based on piperazine and phenothiazines.

The second generation antagonists, which are not sedatives, have a similar structure-activity relationship in that they retain the ethylene base group (alkylamines) or mimic the tertiary amine group with piperazine or piperidine. Examples of Hi antagonists include, without limitation, amelexanox, astemizole. azatadine, azelastine, acrivastine, brompheniramine, cetirizine, levocetirizine, efletirizine, chlorpheniramine, clemastine, cyclin, carebastine, cyproheptadine, carbinoxamine, descarboethoxyloratadine, doxylamine, dimetindena, ebastine, epinastine, efletirizine, fexofenadine, hydroxyzine, ketotifen, loratadine, levocabastine, mizolastine, mequitazine, mianserin, noberastine, meclizine, norastemizole, olopatadine, picumast, pyrilamine, promethazine, terfenadine, tripelenamine, temelastine, trimeprazine and triprolidine, particularly cetirizine, levocetirizine, efletirizine and fexofenadine. Exemplary H antagonists are as follows: Ethanolamines: carbinoxamine maleate, clemastine fumarate, diphenylhydramine hydrochloride, and dimenhydrinate. Ethylenediamines: pyrilamine amleate, tripelenamine HCl, and tripelenamine citrate. Alkylamines: chlorpheniramine and its salts such as maleate salt, and acrivastine. Piperazines: hydroxyzine HCl, hydroxyzine pamoate, cyclizine HCl, cyclizine lactate, meclizine HCl, and cetirizine HCl. Piperidines: Astemizole, levocabastine HCl, loratadine or its analogue of descarboethoxy, and terfenadine hydrochloride and fexofenadine or another pharmaceutically acceptable salt. Azelastine hydrochloride is yet another receptor antagonist \ - which can be used in combination with an inhibitor PDE4. The medication, or one of the medications, may be an H3 antagonist (and / or inverse agonist). Examples of the 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 inverse agonists) of the H4 receptor, for example, the compounds described in Jablonowski et al., J. Med. Chem. 46: 3957-3960 (2003) . As far as the combination products are concerned, the compatibility of the co-formulation is generally determined on an experimental basis by known methods and may depend on the chosen type of action of the drug delivery device. The drug components of a combination product are conveniently selected from the group consisting of anti-inflammatory agents (e.g., a corticosteroid or NSAID), anticholinergic agents (e.g., an M (, M2, M-, / M2 or M3), other ß2 adrenoreceptor agonists, anti-infective agents (for example an antibiotic or antiviral), and antihistamines All suitable combinations are considered Conveniently, compatible components of co-formulation comprise a β2 adrenoceptor agonist and a corticosteroid, and the incompatible component of co-formulation comprises a PDE-4 inhibitor, an anticholinergic, or a mixture thereof, β2 adrenoceptor agonists may for example be salbutamol (eg, as the free base or sulfate salt) or salmeterol (for example as a xinafoate salt) or formoterol (for example as a fumarate salt).

The corticosteroid may, for example, be an ester of beclomethasone (eg, dipropionate) or an ester of fluticasone (eg, propionate) or budesonide. In one example, the compatible components of co-formulation comprise fluticasone propionate and salmeterol, or a salt thereof (particularly the xinafoate salt) and the incompatible component of co-formulation comprises a PDE-4 inhibitor, an anticholinergic (eg, example, ipratropium bromide or tiotropium bromide) or a mixture thereof. In another example, the compatible components of co-formulation comprise budesonide and formoterol (for example 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 delivery to the bronchial or alveolar region of the lung have an aerodynamic diameter of less than 10 microns, preferably 1-6 microns. Other sized particles can be used if delivery to other portions of the respiratory tract is desired, for example the nasal cavity, mouth or throat. The drug can be given as a pure drug, but more appropriately, it is preferred that the drugs be given together with excipients (carriers) that are convenient for inhalation. Suitable 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 powdered medicament and / or excipient can be produced by conventional techniques, for example by micronization, grinding or sieving. In addition, the medicament and / or excipient powders can be designed with densities, size ranges, or particular characteristics. The particles may comprise active agents, surfactants, wall-forming materials, or other components considered desirable by the experts. The excipient can be included with the medicament via well-known methods, for example by mixing, co-precipating and the like. Mixtures of excipients and drugs are commonly 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, thus producing an excipient to drug ratio of 260: 1. Dosage mixtures with drug to drug ratios of 100: 1 to 1: 1 can be used. At very low ratios of excipient to drug, however, the reproducibility of drug doses may reach be more variable. The drug delivery device described herein is in a convenient aspect for the delivery of medicament for the treatment of respiratory disorders such as disorders of the lungs and bronchial tracts including asthma and chronic obstructive pulmonary disorder (COPD). In another aspect, the invention is suitable for the distribution of medicament for the treatment of a condition that requires treatment by systemic circulation of medicament, for example migraine, diabetes, pain relief eg inhaled morphine. Accordingly, the use of the medicament delivery device is provided herein for the treatment of a respiratory disorder, such as asthma and 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 medicament product as described herein of a medicament delivery device in accordance with the present invention. the present. The amount of any particular drug compound or a pharmaceutically acceptable salt, solvate or functional physiological derivative thereof that is required to achieve a therapeutic effect will, of course, vary with the particular compound, route of administration, subject under. treatment, and particular disorder or disease that is treated. Medications for the treatment of respiratory disorders herein may for example be administered by inhalation at a dose of 0.0005 mg to 10 mg, preferably 0.005 mg to 0.5 mg. The dose range for adult humans is generally from 0.0005 mg to 100 mg per day and preferably from 0.01 mg to 1.5 mg per day. It will be understood that the present disclosure is for purposes of illustration only and the invention extends to modifications, variations and improvements thereof. The Request for this description and claims form part of a basis for priority with respect to any subsequent Request. The claims of such subsequent Application may be directed to any feature or combination of features described therein. They may take the form of claims of a product, method or use and may include, by way of example and without limitation, one or more of the following claims.

Claims (56)

1. A conduit for use in a medicament dispensing device for the supply of medicament powder from an open blister-type pocket of a blister-type package, the conduit comprises a body, the body defines a stack having a chimney inlet and a chimney outlet to direct the air flow from the chimney inlet to the chimney outlet; the body further defines a chamber having a chamber inlet and a chamber outlet, wherein the chimney outlet and the chamber inlet are located side by side with each other such that when the blister-type open pocket of the type package blister is placed adjacent to them, the air flow is directed from the chimney outlet to the chamber inlet via the open blister-type pocket to suspend medicament powder and to allow transport thereof in the airflow of the chamber inlet to the chamber outlet, and wherein one or more discharge orifices are provided between the chimney and the chamber such that the suspension air flow can be directed into the chamber to adversely affect the air flow that it carries the medicine powder suspended.

2. A conduit according to claim 1, for use in a dispensing device of medicament for the supply of medicament powder from an open blister-type pocket of each of the plural ampule-type packages, the conduit comprises plural pairs of outputs of chimney and chimney outlets, each of the pairs is associated during use to an open blister-type pocket of a different one from the plural blister-type packs.

A conduit according to any of claims 1 or 2, wherein the conduit is configured such that during use, from 3 to 50% of the total air flow entering the conduit through the chimney inlet, is directed via each chimney outlet to an open blister-type pocket and such that 97 to 50% of the total air flow is directed through one or more discharge orifices to the chamber.

A conduit according to claim 3, wherein the conduit is configured such that during use, from 5 to 25% of the total air flow entering the conduit through the chimney inlet is directed via each outlet of the conduit. chimney to an open blister-type pocket and such that 95 to 75% of the total air flow is directed through one or more discharge orifices to the chamber.

A conduit according to any one of claims 1 to 4, wherein the conduit provides an air flow resistance of 1 to 5 kPa for a total air flow It enters the duct through the chimney entrance at an index of 60 liters / minutes.

6. A conduit according to any of claims 1 to 5, wherein each chimney outlet and / or chamber inlet defines an essentially circular profile, optionally of a diameter of 1 to 7 mm.

7. A conduit according to any of claims 1 to 6 wherein each chimney outlet and / or chamber inlet is provided with a transverse piece passing through it.

8. A conduit according to claim 7, wherein the crosspiece is of a cruciform profile.

A conduit according to any of claims 1 to 8, wherein the chimney and the chamber are located side by side with each other.

A conduit according to any of claims 1 to 8, wherein the chimney and the chamber are located one above the other.

A conduit according to any of claims 1 to 10, wherein the chimney and the chamber share a common wall and at least one or more discharge orifices are provided to the common wall.

12. A conduit according to claim 11, wherein one or more discharge orifices are provided to the common wall.

13. A conduit according to any of claims 1 to 12, wherein one or more discharge orifices have a total cross-sectional area of 1 to 35 mm2, preferably from 10 to 30 mm2.

A conduit according to any one of claims 1 to 13, wherein one or more discharge orifices define a profile selected from the group consisting of circular, D-shaped, oblong-shaped, elongated, and elongated groove profiles.

15. A conduit according to claim 14, wherein one or more discharge orifices define a circular or oval profile and each has a diameter of 1 to 7 mm, preferably 2 to 5 mm.

16. A conduit according to claim 14, wherein one or more discharge orifices define a D-shaped profile and each has a maximum diameter of 1 to 10 mm, preferably 3 to 7 mm.

A conduit according to claim 14, wherein one or more discharge orifices define an elongated groove type profile and each has a length of 1 to 20 mm, preferably 3 to 10 mm and a width of 0.5 to 3 mm, preferably from 0.7 to 2 mm.

18. A conduit according to any of claims 1 to 17, comprising two elongated slot-shaped discharge orifices located parallel to each other. YES.

A conduit according to any of claims 1 to 18, wherein one or more discharge orifices is provided adjacent the chimney outlet and / or the chamber inlet.

A conduit according to any of claims 1 to 18, wherein one or more discharge orifices are separated from the chimney outlet and / or the chamber inlet.

21. A conduit according to claim 20, wherein the separation of one or more discharge orifices from the chamber inlet amounts to at least 10%, preferably to at least 20%, more preferably to at least 30% of length of the camera measured from the camera input to the camera output.

22. A conduit according to any of claims 1 to 21, wherein at least one or more discharge orifices is directed towards an inner wall of the chamber.

23. A conduit according to any of claims 1 to 22, wherein the conduit is made of high density polyethylene.

24. A conduit according to any of claims 1 to 22, wherein the conduit is fully or partially comprised of and / or is coated with a fluoropolymer material.

25. A conduit according to claim 24, wherein the fluoropolymer material comprises multiples of one or more monomer units selected from the group consisting of tetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), perfluoroalkoxyalkane (PFA), ethylene tetrafluoroethylene. (ETFE), vinyldienfluoro (PVDF), tetrafluoroethylene ethylene and any mixture thereof.

26. A conduit according to any preceding claim, wherein the chimney and the chamber are oriented generally perpendicular to each other.

27. A conduit according to any preceding claim, wherein the air flow (suspension air flow) and the discharge air flow are respective portions of the air flow of an inhalation air flow that is withdrawn into the air. conduit through the chimney inlet when an inhalation force is applied to the chamber outlet.

28. A conduit according to any preceding claim, adapted such that in the application of an inhalation force to the chamber outlet, the discharge air flow is greater than the suspension air flow.

29. A conduit according to any preceding claim, wherein the only air entry points in the chamber are one or more chamber inlets, one or more discharge orifices and the chamber outlet.

30. A conduit according to any claim above, where the only air entry points in the chimney are the chimney inlet, one or more discharge orifices and one or more chimney outlets.

31. A conduit according to any preceding claim, which is a one-piece article.

32. A conduit according to any preceding claim which is a molded article.

33. A sub-assembly of the conduit and nozzle comprising a conduit according to any of claims 1 to 32, and a nozzle adjustment thereto which is in communication with the chamber outlet such that inhalation in the nozzle directs the Air flow in the duct through the chimney inlet.

34. An assembly according to claim 33, wherein the nozzle is releasably fitted to the conduit.

35. An assembly according to claim 33 or 34 wherein the conduit and the nozzle are in a snap-fit coupling.

36. A convenient drug dispensing device for the supply of medicament powder of at least one ampule-type package having at least one ampule-type pocket, the dispensing device comprising a conduit according to any of claims 1 to 32

37. A drug delivery device according to claim 36, further comprising a nozzle provided to the conduit.

38. A drug dispensing device according to claim 37, wherein the conduit is located within the housing in an intermediate position between the nozzle and a station to present an open blister-type pocket of at least one blister-type package thereto.

39. A medicament delivery device according to any of claims 36 to 38, further comprising a housing and, within the housing, a mechanism for opening each ampule-type pocket of at least one ampule-type package and presenting each Blister-type open pocket in the chimney exits and in the chamber entrances.

40. A medicament dispensing device according to any of claims 36 to 39, wherein the mechanism comprises an indexing device for indexing the blister-type pockets, one at a time, in the conduit.

41. A medicament delivery device according to claim 40, for use with at least one ampule-shaped package in the form of an elongated strip and having multiple distinct pockets for containing different doses of medicament, wherein the pockets are separated into series along the length of the strip.

42. A medicament delivery device according to any of claims 36 to 41, wherein the The dispensing device is suitable for the simultaneous supply of medicament powder from an open blister-type pocket of each of the plural ampule-type packages.

43. A medicament delivery device according to any of claims 36 to 42, comprising at least one blister-type package containing the medicament in powder form.

44. A medicament delivery device according to claim 43, wherein at least one blister-type package comprises plural ampoules containing the medicament powder.

45. A medicament delivery device according to claim 43 or 44, wherein at least one ampule-type package comprises the plural ampoules containing the medicament powder located in a serial manner in an elongated ampule-type package in Strip shape.

46. A medicament dispensing device according to claim 45, wherein the elongated blister-type package in strip form comprises (a) a base sheet in which the ampoules are formed to define the pockets therein, each contains the powder of medication; (b) a cover sheet that is sealed to the base sheet except in the region of the ampoules and mechanically detached from the base sheet to allow the release of the drug powder.

47. A medicament delivery device according to any of claims 43 to 46, comprising a blister-type package, wherein the medicament powder contained therein comprises a bronchodilator and an anti-inflammatory as active drug components of the drug. same.

48. A medicament delivery device according to any of claims 43 to 46, comprising the first and second blister-type packages, wherein the medicament powder contained in the first blister-type package comprises a bronchodilator while the component Active medicament and medicament powder contained in the second ampule-type package comprise an anti-inflammatory as the active component of medicament.

49. A drug delivery device according to any of claims 47 or 48, wherein the bronchodilator is a beta agonist and an anti-inflammatory is a corticosteroid.

50. A medicament dispensing device according to claim 45, wherein at least one blister-type package has a portion that is adapted during use, which will be longitudinally separated from at least one blister-type package to open the blisters.

51. A medication distributor device in accordance to claim 50, wherein the separable portion is a first portion of at least one blister-type package and at least one blister-type package further has a second portion from which the first portion is separated, the blisters are defined between the first and second portions.

52. A medicament delivery device according to claim 51, wherein the second portion is formed with a series of slits along its length wherein the medicament powder is contained and the first portion provides a cover for each of the cracks.

53. A medicament delivery device according to claim 50, 51 or 52, wherein the separable portion has the first and second ends that are longitudinally separated from each other and the separable portion is separated from at least one blister-type package. extracting the first end longitudinally along at least one blister-type package towards the second end.

54. A medicament delivery device according to any of claims 43 to 46 and 50 to 53, comprising a first and second blister-type packs, each pack having at least one pocket, each containing a medicament powder. inhalable, wherein at least one pocket of the first pack contains at least one medicament that is not in at least one pocket of the second pack.

55. A medication distributor device in accordance to claim 54, wherein the powder of inhalable medicament in each packet is for the treatment of a respiratory disease.

56. Use of a medicament delivery device according to any of claims 36 to 55 for distributing a medicament product.