Powder dispensing and sensing apparatus and methods

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DESCRIPTION

Dust detection and dispensing apparatus and procedures.

Field of the invention

This invention relates to methods and apparatus for dispensing and detecting powder, and more particularly to methods and apparatus for dispensing precisely controlled amounts of powder into multiple cartridges and for individually detecting the fill status of each. cartridges. Such a method and apparatus is known from US 4127054. The powder can contain a medicament and the cartridges can be used in an inhaler. However, the invention is not limited to this application.

Background of the invention

It has been proposed to deliver certain types of drugs to patients by inhalation of powder as a delivery mechanism. A particular example uses diketopiperazine microparticles known as Technosphere microparticles^®. Technosphere particles have a platelet surface structure and can be loaded with a drug. See, for example, US Patent No. 5,352,461, issued October 4, 1994 to Feldstein et al .; US Patent No. 5,503,852, issued April 2, 1996 to Steiner et al .; US Patent No. 6,071,497, issued June 6, 2000 to Steiner et al .; US Patent No. 6,428,771, issued August 6, 2002 to Steiner et al .; US Patent No. 6,444,226, issued September 3, 2002 to Steiner et al .; and US Patent No. 6,652,885, issued November 25, 2003 to Steiner et al. One use for these microparticles is the delivery of insulin by inhalation. An inhaler featuring a replaceable cartridge or capsule containing the drug powder is used for the delivery of drugs.

Administering medications by inhalation typically requires a very small amount of powder in the inhaler cartridge. As an example, insulin delivery using Technosphere particles may require as little as 10 milligrams of powder. Also, the dosage of the drug must be quite accurate. A lower than specified dose may not have the desired therapeutic effect, while a higher than specified dose may have a negative effect on the patient. Additionally, although Technosphere microparticles are highly effective for inhalation drug delivery, their platelet surface structure makes Technosphere powder cohesive and somewhat difficult to handle.

In the commercialization of the supply of medicinal products by inhalation, a large number of cartridges containing the medicinal product must be produced efficiently and economically. A precise dose of powder must be delivered in each cartridge and the dose of medication must be verified in each cartridge. Manufacturing techniques and equipment must have high production capacity to meet demand and must be able to handle powder that is cohesive and therefore does not flow freely. Current manufacturing techniques and equipment have not proven adequate to meet these demands.

Therefore, novel methods and apparatus are needed to detect and dispense the powder.

Summary of the invention

Systems and procedures are provided to simultaneously dispense precisely controlled doses of powder into multiple cartridges. The powder can contain a medicine and the cartridges can be used in inhalers. The fill status of each cartridge, typically the weight of the powder, is sensed during filling, and the powder dispensing modules are individually controlled in response to the sensed weight to ensure an accurate dose. The system operates at high speed and can be very compact to allow filling operations with minimal space requirements.

According to a first aspect of the invention, a powder dispensing and detecting apparatus comprises a tray support structure for housing a cartridge tray containing cartridges, a powder dispensing assembly including powder dispensing modules for dispensing powder on respective cartridges from a batch of cartridges in the cartridge tray, a powder transport system for supplying powder to the powder dispensing modules, a detection module that includes detection cells for detecting respective fill states of each of the cartridges of the cartridge batch, wherein the detection cells are configured to individually detect the fill status of each of the cartridges during powder dispensing, and a control system for controlling the powder dispensing modules in response to the respective sensed fill states of each of the cartridges in the cartridge batch, so that powder dispensing can end when a quantity of powder has been dispensed. desired on each cartridge.

The powder dispensing modules, the powder transport system, and the sensing cells can be configured to concurrently dispense the powder in the batch of cartridges and to concurrently detect the fill status of each of the cartridges in the batch of cartridges. The detection cells may comprise weight detection cells. The cartridge tray can be configured to support the cartridges in a two-dimensional array of rows and columns.

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The powder transport system may include a blower assembly for moving a transport gas, a powder aerator for supplying powder to the powder dispensing assembly, and a hopper assembly for supplying powder to the powder aerator. The powder transport system may further include a manifold that couples the transport gas from the powder dispensing assembly to the blower assembly to form a closed loop recirculating gas transport system. The powder transport system may include a transport gas conditioning system to control the relative humidity, temperature, or both, of the transport gas.

Each of the powder dispensing modules may include a housing that defines a powder inlet for receiving powder from the powder transport system, a powder outlet, and a powder supply conduit that connects the powder inlet and the powder outlet, and a feed mechanism to move the powder through the chute from the powder inlet to the powder outlet.

The feed mechanism may include a feed rod to move the powder through the conduit, an actuator to operate the feed rod, a valve to control the output, and an actuator to operate the valve. The feed rod may include a shaft and a helical three-dimensional structure that includes separate bars attached to the shaft. The spaced bars may have a helical arrangement on the shaft. The feed rod may further comprise an arrangement of one or more wires attached between some or all of the spaced bars. The wires can include one or more helical arrangements attached between the ends of the bars and one or more chevron arrangements attached between the bars at selected radial locations. In some embodiments, each wire is slidably attached through holes in intermediate bars and is coupled at each end to one of the bars.

The feed rod further includes a discharge element attached to the shaft below the helical three-dimensional structure. In different embodiments, the discharge element can be implemented as a modified rod having a double helix configuration, a cylindrical pin and a support element used in combination with a hole element or auger blades used in combination with a hole element. .

The powder dispensing assembly may include a die block having a vertical hole die. The powder dispensing modules can be mounted in respective vertical holes of the die block. The die block may include channels for supplying powder to the powder dispensing modules. The powder dispensing modules may be provided with powder inlets aligned with the channels of the die block so that the powder is supplied to a row of powder dispensing modules through a channel of the die block. Each channel of the die block can pass through the die block to circulate new transport gas to the blower assembly. The channels of the die block may have sufficient capacity to store powder during one or more powder dispensing cycles of the powder dispensing modules.

The hopper assembly may include a hopper body that defines a powder bin and a granulator at the bottom of the powder bin. The granulator may comprise a first and a second agglomeration roller and a first and a second motor for driving the first and second agglomeration rollers, respectively. Each of the agglomeration rollers may be provided with a plurality of pins or with a plurality of separate discs.

The blower assembly may include a blower for moving a transport gas through a recirculating transport gas system and a gas particle separator for removing dust agglomerates from the recirculating transport gas. In some embodiments, the gas particle separator is implemented as a cyclone separator and in other embodiments the gas particle separator is implemented as a vane separator. The blower may include an impeller to move the transport gas, an impeller motor to rotate the impeller, and a blower housing containing the impeller and having a discharge port for supplying the transport gas to the dust aerator. The blower assembly may further comprise an induction rod for introducing the conditioned transport gas into the flow of the transport gas.

The dust aerator may include a collector block that defines a dust inlet, dust outlet ports coupled to the powder dispensing assembly, and a gas inlet coupled to the blower assembly. The dust aerator may further include an air broom for supplying dust through risers to the dust outlet ports and a dump valve for supplying a quantity of dust from the dust inlet to the air broom. The drain valve also seals the closed loop transport gas system from the outside environment. The dust aerator may further include a bypass manifold coupled to the dust outlet ports and a bypass valve that directs selected portions of the transport gas from the gas inlet to the air broom and bypass manifold.

According to a second aspect of the invention, there is provided a method for dispensing and detecting powder. The method comprises placing cartridges in a cartridge tray, concurrently dispensing powder into a batch of cartridges from the cartridge tray, and concurrently detecting a fill status of each of the cartridges in the cartridge batch during dispensing of the powder, so that powder dispensing can end when a desired amount of powder has been dispensed into each cartridge.

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According to another aspect of the description, a dust aerator comprises a collector block defining a dust inlet, dust outlet ports and a transport gas inlet; a pneumatic broom for supplying powder to the powder outlet ports; a dump valve for supplying a quantity of powder from the powder inlet to the air broom; a bypass collector coupled to the powder outlet ports; and a bypass valve for directing selected portions of the transport gas from the gas inlet to the air broom and the bypass manifold.

According to another aspect of the description, a powder dispensing assembly comprises a die block that includes a matrix of vertical holes and horizontal channels crossing each of the vertical holes; and powder dispensing modules mounted in respective vertical holes of the die block, each of the powder dispensing modules presenting powder inlets communicating with the channels of the die block, wherein the powder supplied to the channels of the die block die block are dispensed by each of the powder dispensing modules.

According to another aspect of the description, a powder transport system comprises a powder dispensing assembly for dispensing powder into cartridges; a blower assembly for moving a transport gas; and a powder aerator for supplying entrained powder in the transport gas to the powder dispensing assembly.

According to another aspect of the description, a powder dispensing module comprises a housing defining a powder inlet for receiving powder, a powder outlet, and a powder supply conduit connecting the powder inlet and the powder outlet; a feed rod for moving powder through the powder supply conduit; an actuator for operating the feed rod; a valve to control the output of powder; and an actuator to operate the valve.

According to another aspect of the description, a blower assembly comprises an impeller for displacing a transport gas; an impeller motor for rotating the impeller; a blower housing containing the impeller and having a discharge port for the transport gas; a manifold to receive transport gas; and a gas particle separation device attached to the manifold to accumulate agglomerates entrained by the transport gas.

According to another aspect of the description, a dust treatment apparatus comprises a tray support structure for housing a cartridge tray containing at least a first batch of cartridges and a second batch of cartridges; a dispensing subsystem for dispensing powder into a batch of the cartridges from the cartridge tray; and a tray positioning mechanism for moving the cartridge tray to sequentially position the first and subsequent batches of cartridges from the cartridge tray in alignment with the dispensing subsystem.

According to another aspect of the description, a method of dispensing powder into a cartridge comprises placing a cartridge under a dispensing module having a hopper containing powder, opening a valve that controls the hopper, operating a feed rod in the hopper to dispense powder to the cartridge through the valve, and close the valve when the desired fill state of the cartridge has been reached.

Operation of the feed rod may include rotating the feed rod and reversing the rotation of the feed rod to condition the powder in the hopper. The feed rod can be rotated at variable speeds and can be shaken during rotation. The feed rod can reciprocate, causing the rod to rotate rapidly clockwise and counterclockwise for some portion of one or more revolutions. The procedure may include sensing the weight of the powder in the cartridge and closing the valve when the sensed weight is equal to or greater than a target weight. Opening the valve may include rotating a valve member in a selected direction, and closing the valve may include rotating the valve member in the same direction. Opening the valve may include placing the valve member posterior to the dispensing nozzle opening.

The feed rod may be rotated at a selected maximum speed during a first portion of a fill cycle and then rotated at a reduced speed during a second portion of the fill cycle. The second portion of the fill cycle can be started when the amount of powder dispensed into the cartridge is equal to or greater than a selected weight. Proportional control and / or integral control can be used during any portion of the fill cycle.

According to another aspect of the invention, the powder dispensing and detecting apparatus is a highly compact modular system that can be operated both in a research laboratory and in a production plant. This feature facilitates regulatory approval for a common machine resulting in reduced costs due to common technical support and reduced refinement and parts inventories.

According to another aspect of the invention, the powder dispensing and detecting apparatus has the ability to fill inhaler cartridges, single-use inhalers, and multi-use compact inhalers. This capability can be achieved by relatively minor changes to the system supplying containers to be filled with the powder detecting and dispensing apparatus.

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Brief description of the drawings

For a better understanding of the present invention, reference is made to the attached drawings that are incorporated herein by reference and in which:

fig. 1 is a perspective view of a powder detecting and dispensing apparatus according to an embodiment of the invention;

fig. 2 is an exploded view of the powder detecting and dispensing apparatus of FIG. 1;

fig. 3 is a partial vertical cross-sectional view of the powder dispensing and detecting apparatus;

fig. 3A is a schematic block diagram of the powder dispensing and detecting apparatus;

fig. 4 is a perspective view of powder dispensing modules, cartridges, a cartridge tray, and weight sensing cells;

fig. 5 is a perspective view of a powder transport system;

fig. 6 is a cross-sectional diagram of a die block and a powder transport system;

fig. 7 is a cross-sectional diagram of a cartridge tray and tray positioning system;

fig. 8 is a perspective view of a die block;

fig. 9 is an exploded view of the die block of FIG. 8;

fig. 10 is a perspective view of a powder dispensing module;

fig. 11 is an exploded view of the powder dispensing module of FIG. 10;

fig. 12 is a schematic cross-sectional diagram of the lower end of the powder dispensing module;

figs. 13A and 13B illustrate a feed rod according to one embodiment of the invention;

figs. 14A through 14F illustrate a feed rod according to another embodiment of the invention;

figs. 15A to 15D illustrate a feed rod according to a further embodiment of the invention;

figs. 16A and 16B illustrate a fill valve in the open and closed positions, respectively;

fig. 17 is a block diagram of a control circuit for a single powder dispensing module and a weight sensing cell;

fig. 18 is a flow chart of a powder dispensing process;

fig. 19 is a flow chart of a cartridge fill cycle;

fig. 20 is a perspective view of the detection module;

fig. 21 is an exploded view of the detection module of FIG. twenty;

fig. 22 is a perspective view of a first embodiment of a weight sensing probe;

fig. 23 is a perspective view of a second embodiment of a weight sensing probe;

fig. 24 is a perspective view of a first embodiment of a dust aerator;

fig. 25 is an exploded view of the dust aerator of FIG. 24;

fig. 26 is a perspective view of an air broom used in the dust aerator of FIG. 24;

fig. 27 is an exploded view of the air broom of FIG. 26;

figs. 28A through 28C are cross-sectional views of the dust aerator of FIG. 24;

ES 2 332 292 T3 FIG. 29 is a perspective view of a second embodiment of a dust aerator;

fig. 30 is an exploded view of the dust aerator of FIG. 29;

fig. 31 is a perspective view of an air broom used in the dust aerator of FIG. 29;

fig. 32 is an exploded view of the air broom of FIG. 31;

fig. 33 is a perspective view of a first embodiment of a hopper assembly;

fig. 34 is an exploded view of the hopper assembly of FIG. 33;

fig. 35 is a perspective view of a second embodiment of a hopper assembly;

fig. 36 is an exploded view of the hopper assembly of FIG. 35;

fig. 37 is a perspective view of a first embodiment of a blower assembly;

fig. 38 is an exploded view of the blower assembly of FIG. 37;

fig. 39 is a perspective view of a second embodiment of a blower assembly;

fig. 40 is an exploded view of the blower assembly of FIG. 39;

fig. 41 is a schematic diagram of a gas conditioning system;

fig. 42 is a perspective view of a powder supply system incorporating a detection chamber; fig. 43 is an exploded view of the detection chamber shown in FIG. 42;

fig. 44 is an illustrated representation of a filling process for an inhaler cartridge; and fig. 45 is an illustrated representation of a filling process for a compact inhaler.

Detailed description

Figs. 1 to 7 show a powder dispensing and detecting apparatus 10 according to one embodiment of the invention. An object of the apparatus is to dispense powder into multiple cartridges 20 and to detect and control a fill state of each of the cartridges so that each of the cartridges receives a precisely controlled amount of powder. As used herein, the term "cartridge" refers to any container or capsule that can contain powder, typically powder containing a drug. As used herein, the term "filled" includes full and partially full, as each cartridge is not normally filled to its full capacity and, in fact, can only be filled to a small fraction of its capacity. As will be described later, the apparatus can be used to fill an inhaler cartridge or compact inhaler, but is not necessarily limited to the type of container to be filled.

Cartridges 20 may be arranged in a cartridge tray 22 that is located on a tray support structure 24 for processing. The cartridges can be arranged in a matrix of rows and columns. In one example, a cartridge tray 22 contains forty-eight cartridges 20 in a 6x8 matrix. The configuration of the cartridge tray 22 and the corresponding configuration of the apparatus 10 are provided by way of example only and do not limit the scope of the invention. It should be understood that the cartridge tray 22 may be configured to contain a different number of cartridges and that the cartridge tray 22 may have a different matrix configuration within the scope of the invention. In another embodiment described later, the cartridge tray can hold 192 cartridges. The cartridge tray 22 can be placed on a support frame 24 and removed from the support frame 24 by a robot.

The components of the powder dispensing and detecting apparatus 10, in addition to the tray support structure 24, include a powder dispensing assembly 30 for dispensing powder into cartridges 20, a powder conveying system 32 for supplying powder to the assembly. 30 dispensing powder and a detection module 34 for detecting a fill status of each of the cartridges 20. The powder sensing and dispensing apparatus 10 further includes a frame 40 for mounting the tray support frame 24, the powder dispensing assembly 30, the powder conveying system 32 and the sensing module 34, and actuators 42 to move the powder dispensing assembly 30 and the powder transport system 32 relative to the cartridges 20.

The powder dispensing assembly 30 includes a die block 50 having a vertical hole die 52 and a powder dispensing module 54 mounted in each of the vertical holes in the die block 50. The die block 50 may be configured to match the cartridge die 20 in the tray.

ES 2 332 292 T3 cartridges or with a subset of the cartridges in the cartridge tray. In the above example of a cartridge tray containing forty-eight cartridges, die block 50 may have a 6x8 die of vertical holes 52 and provides support for forty-eight powder dispensing modules 54. In this embodiment, the powder dispensing modules 54 are mounted on 2.54 cm (one inch) centers. It should be understood that a different separation arrangement may be used within the scope of the invention. As shown in fig. 8, matrix block 50 further includes powder transport and storage channels 60a, 60b, 60c, 60d, 60e, 60f, 60g, and 60h, with one channel for each row of six powder dispensing modules 54 in this embodiment. The powder is supplied by the powder transport system 32 to the powder dispensing modules 54 through each channel of the die block 50, as will be described later. Preferably, each channel has a volume sufficient to store powder for several powder dispensing cycles.

In the embodiment of Figs. 1 to 7, the powder transport system 32 includes a first powder transport system 32a for supplying powder to a first group of four channels 60a, 60b, 60c, and 60d of the die block 50 and a second powder transport system 32b. powder for supplying powder to a second group of four channels 60e, 60f, 60g and 60h of the matrix block 50. Each of the powder conveying systems 32a and 32b includes a blower assembly 70 for moving a conveying gas through the powder conveying system, a powder aerator 72 for supplying powder to the powder dispensing assembly 30, and an assembly 74 hopper for supplying powder to a powder aerator 72. In other embodiments, a single powder transport system or more than two powder transport systems may be used.

Blower assembly 70 is coupled via tube 76 to gas inlet 78 of dust aerator 72 and generates a flow of transport gas through gas inlet 78. The dust aerator 72 includes a dust inlet 80 for receiving dust from the hopper assembly 74. The powder is supplied by the powder aerator 72 through four powder outlet ports 82 to respective channel inlet ends of the die block 50. The powder is conveyed through the respective channels to the powder dispensing modules 54 of each row of the powder dispensing assembly 30. The powder is individually dispensed into cartridges 20 via powder dispensing modules 54 as will be described later.

Channels 60a to 60h traverse die block 50 and a matched suction manifold 84 is coupled to outlet ends of the channels. The suction manifold 84 of the first powder transport system 32a is connected to outlet ends of the channels 60a to 60d, and the suction manifold 84 of the second powder transport system 32b is connected to the outlet ends of the channels. 60e to 60h. Suction manifold 84 returns transport gas to blower assembly 70 thereby forming a closed loop recirculating gas transport system. In other embodiments, the powder transport system can use an open loop gas transport system. Any amount of powder not supplied to the powder dispensing modules 54 or stored in the channels returns to the blower assembly 70 through the suction manifold 84. As will be discussed later, the blower assembly 70, in some embodiments, may include a gas particle separator to retain large agglomerates of powder, while small agglomerates of powder are circulated back to the aerator 72. of powder for supply to the powder dispensing assembly 30. As will be discussed further below, each powder transport system may include a gas conditioning unit to control the relative humidity and / or temperature of the recirculating transport gas.

The powder transport system 32 may include detectors to determine the level of powder in different components of the powder transport system. The hopper assembly 74 may include a hopper level detector to detect the level of dust in the reservoir of the hopper assembly 74. The dust aerator 72 may include a dump valve level detector to determine the level of dust in the dust aerator 72 dump valve. Blower assembly 70 may include a large agglomerate level detector. A dispensing fill level detector may be located in the suction manifold 84 of the blower assembly 70. Dust level detectors can use optical techniques to detect dust level, for example. The powder level detectors can be used to monitor the operation of the powder supply system 32 and charge the powder dispensing modules 54 with powder.

The detection module 34 (FIG. 20) may include a detection housing 100 (FIG. 21) and an array of detection assemblies 110 mounted in the detection housing 100. In the illustrated embodiment, each of the sensing assemblies 110 includes two sensing cells 114 (FIG. 3) and associated circuitry. Therefore, a detection assembly 110 is used with two powder dispensing modules 54. In other embodiments, each detection set can include a single detection cell or more than two detection cells. The number of sensing assemblies 110 and the arrangement of sensing assemblies 110 in the array may be such that sensing cells 114 match the configuration of cartridges 20 in cartridge tray 22 or a subset of the cartridges of the cartridge tray. For the example of a cartridge tray 22 containing forty-eight cartridges 20 in a 6x8 matrix on 2.54 cm (one inch) centers, the sensing module 34 may include twenty-four sensing assemblies 110 providing forty-eight Detection cells 114 in a 6x8 array on 2.54 cm (one inch) centers. In the embodiment of Figs. 1 through 7, each of the detection cells 114 is a weight detector for detecting the weight of the powder supplied to the respective cartridge 20. A weight sensing probe 112 is attached to each of the sensing cells 114 and contacts a lower end of the cartridge 20 through an opening in the cartridge tray 22.

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The sensing cells 114 individually detect the fill status of each of the cartridges 20 during powder dispensing, so that powder dispensing can end when the desired amount of powder has been dispensed into each cartridge 20. Detection cells 114 are preferably weight detectors that monitor the weight of the cartridge 20 during the powder dispensing process and have an accuracy of 5 to 10 micrograms in the present embodiment. An electrical balancing beam is typically used as a weight detector in applications that require high precision, high speed, and repeatability with very small weights.

The physical configuration of the weight sensing assembly 110 is a consideration in systems where the powder dispensing modules 54 are in close proximity to each other, such as on 2.54 cm (one inch) centers. Preferably, the weight sensing assemblies 110 may be placed in a matrix that matches the configuration of the cartridge tray 22 and the powder dispensing modules 54. In a preferred embodiment, the sensing assemblies 110 have a vertical configuration and two sensing cells 114 that are packed together to form a sensing assembly. The weight sensing mechanical components are located at the top of the assembly, the electrical circuitry is located below the mechanical components, and an electrical connector is located at the bottom. The sensing assemblies can be mounted in a die to detect weight in 2.54 cm (one inch) centers.

In another embodiment, a commercially available weight sensing module has a horizontal configuration and can be used in a tiered arrangement of three different levels for an array that has six cartridges per row. In the tiered arrangement, probes of different lengths are used to make contact with the cartridges.

Dust sensing and dispensing apparatus 10 has been described featuring powder dispensing modules 54 and sensing cells 114 mounted on 2.54 cm (one inch) centers. It should be understood that greater or lesser spacing between the components may be used within the scope of the invention. Furthermore, the components of apparatus 10 are not necessarily assembled in a uniform matrix. For example, the component spacing in the x direction may be different from the component spacing in the y direction, or a row in the matrix may be offset from an adjacent row.

In operation, the cartridge tray 22 containing cartridges 20 is positioned on the tray support structure 24, preferably by a robot or other automatic mechanism. Cartridge tray 22 descends such that cartridges 20 rise from cartridge tray 22 via weight sensing probes 112 of respective sensing assemblies 110 and are supported by probes 112. Cartridge tray 22 may be provided with openings at each cartridge location to allow probes 112 to pass through cartridge tray 22 and lift cartridges 20. Thus, each cartridge 20 can be weighed by one of the sensing cells 114 No interference with cartridge tray 22. In some embodiments (Figs. 22 and 23), probe 112 includes and a three-point holder for cartridge 20. In other embodiments, probe 112 includes a cylindrical holder for cartridge 20. Powder dispensing assembly 30 descends to a dispensing position. In the dispensing position, each powder dispensing module 54 is positioned slightly above and aligned with one of the cartridges 20.

As shown in fig. 2, a frame 40 may include a lower frame 40a, a central frame 40b, and an upper frame 40c. The lower structure 40a and the central structure 40b are fixed to a base plate 41. The upper structure 40c provides a support for the tray support structure 24, for the powder dispensing assembly 30, and for the powder transport system 32. Die block 50 is connected to actuators 42 and moves up or down when actuators 42 are activated. Detection module 34 is mounted in a fixed position on lower frame 40a and central frame 40b.

As will be discussed later, the powder transport system 32 can be operated continuously or at intervals. Powder dispensing modules 54 are activated to dispense powder to cartridges 20. Powder dispensing to cartridges 20 occurs concurrently, such that all cartridges in cartridge tray 22 or a subset of cartridges in tray of cartridges receive powder simultaneously. As powder dispensing progresses, the weight of cartridges 20 is sensed by respective sensing cells 114. The output of each detection cell 114 is coupled to a controller. As will be discussed later, each controller compares the detected weight with a target weight that corresponds to the desired amount of powder. The powder dispensing process continues as long as the detected weight is less than the target weight. When the detected weight is equal to or greater than the target weight, the controller commands the corresponding powder dispensing module 54 to end the powder dispensing operation. If the detected weight exceeds a maximum allowable weight after the fill cycle, the corresponding cartridge may be marked as defective. Therefore, powder dispensing and weight detection are carried out concurrently for a batch of cartridges from the cartridge tray 22. The lot can include all of the cartridges in cartridge tray 22 or a subset of the cartridges in the cartridge tray. A powder dispensing cycle may include concurrent dispensing of powder into and weight detection of a batch of cartridges and achieving 100% inspection and control of powder dispensing.

In one embodiment, the number and spacing of cartridges in cartridge tray 22 match the number and spacing of powder dispensing modules 54 in apparatus 10. In other embodiments, the cartridge tray may have a different number. cartridges and a gap between cartridges that is different from

ES 2 332 292 T3 the configuration of the powder dispensing modules 54. For example, the cartridge tray may be configured to hold a multiple of the number of powder dispensing modules 54 and have a smaller spacing between cartridges than the spacing between powder dispensing modules 54. By way of example only, the cartridge tray can be configured to hold 192 cartridges 20 spaced on 1/2 inch centers. With this arrangement, a 12x16 array of cartridges on 1/2 inch centers occupies the same area as a 6x8 array of cartridges on 2.54cm (one inch) centers.

As shown in fig. 7, the cartridge tray 22 can be moved in a horizontal direction by a tray positioning mechanism 120 to align different batches of cartridges with the powder dispensing modules 54. The cartridge tray 22 is positioned on a tray support structure 24 for processing. The tray positioning mechanism 120 includes an X direction actuator 230 coupled to tray support structure 24 and a Y direction actuator 232 coupled to tray support structure 24. Therefore, the tray support structure 24 and the cartridge tray 22 can move in a horizontal XY plane to position the cartridge batches with respect to the powder dispensing modules 54 and sensing cells 114.

The cartridge tray with 192 cartridges can be processed as follows. The cartridge tray is moved from a neutral position to a first XY position (0,0) such that a first batch of 48 cartridges is vertically aligned with the matrix of 48 powder dispensing modules 54. The powder is dispensed into the first batch of cartridges and then the cartridge tray is moved to a second XY position (0.50) to align a second batch of 48 cartridges with the 48-module array 54 of powder dispensing. The powder is dispensed into the second batch of cartridges and then the cartridge tray is moved to a third XY position (0.5, 0) to align a third batch of 48 cartridges with the 48-module array 54 of powder dispensing. The cartridge tray is then moved to a fourth XY position (0.5, 0.5) to align a fourth batch of 48 cartridges with the array of 48 powder dispensing modules 54. The powder is dispensed into the fourth batch of cartridges to complete processing of all 192 cartridges. In the example above, the order of the tray positions and the order of the cartridge batches can be changed.

It should be understood that this process can be applied to different tray arrangements with a different spacing between cartridges, with a different number of cartridges, etc. In these embodiments, the cartridge tray is moved in the horizontal plane to achieve alignment between the cartridge batches and the array of powder dispensing modules. The cartridge lot typically matches the array of powder dispensing modules 54. However, in some applications, the batch may have fewer cartridges than the number of powder dispensing modules.

Figs. 8 and 9 show matrix block 50. As previously described, the matrix block 50 is provided with channels 60a, 60b, 60c, 60d, 60e, 60f, 60g and 60h for transporting and storing powder, one channel corresponding to each row of the matrix of modules. 54 powder dispensing. Each of the channels 60a to 60h extends through the die block 50 and crosses the vertical holes 52 of the corresponding row of the die. In the embodiment of Figs. 1 At 7, the powder transport system 32a supplies powder to one side of the die block 50, and the powder transport system 32b supplies powder to the opposite side of the die block 50. Thus, figs. 8 and 9 show the inlet ends of channels 60a through 60d and the outlet ends of channels 60e through 60h.

In the embodiment of Figs. 8 and 9, channels 60a to 60h have slot-shaped cross sections and are parallel. As shown in fig. 10, each of the powder dispensing modules 54 is provided with a powder inlet 130 in the form of a slot-shaped opening through the powder dispensing module. When the powder dispensing modules 54 are mounted in the die block 50, the powder inlets 130 are aligned with the corresponding channel of the die block 50. The dust inlets 130 and channels 60a through 60h preferably have cross sections of the same size and shape and are polished to provide smooth interior surfaces. Each channel of the matrix block 50 and the corresponding powder inlets 130 of the powder dispensing modules 54 define a passage through the matrix block 50 for the supply of powder to each of the powder dispensing modules 54. Powder is supplied to each of the powder dispensing modules 54 through the powder inlet 130. The powder inlet 130 is configured as a through opening such that some of the powder carried through the channel is supplied to the first powder dispensing module 54 and some of the powder is conveyed through the powder inlet 130 and the channel from matrix block 50 to successive powder dispensing modules 54.

In addition, channels 60a to 60h have a powder storage function. Channels 60a to 60h can store a quantity of powder greater than is necessary for dispensing in a single batch of cartridges. In one embodiment, the powder transport system 32 operates at intervals. A sufficient quantity of powder for a plurality of batches of cartridges 20 is supplied from hopper assembly 74 to channels 60a through 60h. The powder is then dispensed to several batches of cartridges 20 until the supply of powder in the dispensing modules 54 becomes low. In other embodiments, the powder is constantly supplied to channels 60a through 60h, and channels 60a through 60h serve as intermediate reservoirs for storing non-dispensed powder in cartridges 20.

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The closed loop pneumatic powder transport system 32 introduces the agglomerate particles into the die block 50 from the powder aerator 72. The transport gas is then circulated back to the dust aerator 72. The transport gas can be conditioned by a secondary process control gas that is supplied to the blower assembly 70.

The matrix block 50 functions as a dynamic powder storage device that introduces batch loads or continuous loads of drug powder into individual powder dispensing modules 54. More generally, die block 50 includes one or more channels that are used to convey powdered aerosols and / or drug powder agglomerate slurries to an array of powder dispensing modules. The die block 50 can be operated in an open loop or closed loop gas transport system. The powder aerator 72 and die block 50 fluidize, entrain, and transport drug powder into the channels of die block 50.

Die block 50 can provide the primary structural support for associated components and subsystems, such as dust aerator 72, hopper assembly 74, suction manifold 84, and pump assembly 70. In addition, die block 50 contains an array of powder dispensing modules 54 for dispensing powder into a cartridge array. In a preferred embodiment, the die block includes a main block 132, an upper plate 134, and a lower plate 136. Plates 134 and 136 include O-rings that serve as guides and seals for powder dispensing modules 54. This die block further includes bearings 140 and clamping handles 142 for coupling the die block to frame members.

In operation, the powder is transported through each of the channels 60a to 60h by the transport gas and supplied to each of the powder dispensing modules 54 in a controlled particle deposition process. The powder falls under the action of gravity into each of the powder dispensing modules 54. Any powder that passes through the channel without falling into one of the powder dispensing modules 54 and that is not stored returns through the suction manifold 84 to the pump assembly 70.

Each powder dispensing module 54 dispenses powder into a cartridge 20. The powder dose is typically within a range of 5 to 30 milligrams, but the dose is not limited to this range.

As shown in detail in figs. 10 to 16B, the powder dispensing module 54 includes a powder dispensing housing 150 having a lower housing section 150a, a central housing section 150b, an upper housing section 150c, and a cover 150d. The powder dispensing housing 150 may have an elongated configuration with a small cross section to allow a short gap distance in the die block 50. As noted above, the powder dispensing modules 54 can be mounted on 2.54 cm (one inch) centers. The central housing section 150b includes a powder inlet 130 and a cylindrical conduit 152 that extends downwardly from the powder inlet 130 to the lower housing section 150a. The lower housing section 150a includes a tapered conduit 154 that extends downwardly to a dispensing nozzle 158 that is dimensioned to be compatible with cartridge 20. Tapered conduit 154, which may have a conical shape, provides a transition from the dimension of cylindrical conduit 152 to the dimension of dispensing nozzle 158. Together, cylindrical conduit 152 and tapered conduit 154 define a dispensing hopper 156 that contains the powder to be dispensed. The powder in the dispensing hopper 156 is referred to as a bulk powder bed. Dispensing nozzle 158 is configured to dispense powder into cartridge 20.

Powder dispensing module 54 further includes a feed wand 160 for moving powder down in a controlled manner through dispensing hopper 156 to nozzle 158, a wand actuator 162 for actuating wand 160, a valve Dispense fill 180 at the lower end of hopper 156, and a valve actuator 182 for opening and closing valve 180. Rod actuator 162 and valve actuator 182 may be miniature motors. Rod actuator 162 may be coupled to feed rod 160 by flexible coupling 186 or other coupling that can provide displacement, vertical agitation of the rod, or both, in addition to rotation. The powder dispensing module 54 further includes a circuit board 184 that contains circuitry for controlling the wand actuator 162 and the valve actuator 182 and for communicating with the control circuitry that controls the operation of the module 54. of powder dispensing.

The fill valve 180 may include a valve member 190 implemented as a gear provided with an eccentrically located valve opening 191. Valve member 190 can be mounted in lower housing section 150a to rotate about an axis so that valve opening 191 can rotate to align with dispensing nozzle 158, as shown in FIG. 16A, and can be rotated to be misaligned with the dispensing nozzle 158, as shown in FIG. 16B. When the valve opening 191 and the dispensing nozzle 158 are aligned or partially aligned, the fill valve 180 opens and the powder is dispensed into a cartridge. When the valve opening 191 is not aligned with the dispensing nozzle 158, the fill valve 180 closes and the powder is not dispensed. Preferably, the fill valve 180 is a partially openable type, as will be described later.

The valve member 190 of the fill valve 180 may be coupled to the valve actuator 182 by a drive assembly that includes a lower gear 192 meshed with the gear of the valve member 190

ES 2 332 292 T3 valve, a drive shaft 193 extending from a lower part of the dispensing module 54 to an upper part thereof where the valve actuator 182 is mounted, an upper gear 194 coupled to the upper end of the shaft 193 drive and an upper gear 195 coupled to valve actuator 182. Upper gears 194 and 195 are meshed with each other so that valve member 190 is rotated when valve actuator 182 is activated.

Gear 195 may be aligned with valve member 190, and gear 194 may be aligned with gear 192. Therefore, the position of gear 195 is indicative of the position of valve member 190 and the position of the valve. valve opening 191 with respect to nozzle 158. A magnet coupled to upper gear 195 rotates with respect to open and close detectors 220 (fig. 17) to indicate the open and closed positions, respectively, of the fill valve 180.

Fig. 12 shows a schematic cross-sectional diagram of the lower end of the powder dispensing module 54, between the powder inlet 130 and the dispensing nozzle 158. As shown, the dispensing hopper 156 can be considered to have a powder bed preparation zone 156a, a powder bed compression zone 156b, and a discharge zone 156c. The powder bed preparation zone 156a is located in the cylindrical conduit 152 below the powder inlet 130. The powder bed compression zone 156b is located in an upper portion of the tapered conduit 154, and the discharge zone 156c is located in a lower portion of the tapered conduit 154.

Feed rod 160 may include a rod-shaped shaft 170 that extends axially through dispensing hopper 156. The feed rod 160 further includes one or more feed elements attached to the shaft 170. The feed elements move the powder from the powder inlet 130 to the dispensing nozzle 158 in a controlled manner. In the embodiment of fig. 12, the feed rod 160 includes a powder bed preparation element 164 in the powder bed preparation zone 156a, a powder bed compression element 165 in the powder bed compression zone 156b, and an element 166 discharge in discharge zone 156c. Examples of feed elements 164, 165 and 166 will be described later.

One embodiment of feed rod 160 is shown in FIGS. 13A and 13B. In the feed rod embodiments described herein, the powder bed preparation element 164 and the powder bed compression element 165 are implemented as a helical three-dimensional structure that includes a plurality of separate bars 172 mounted on the shaft 170 and one or more wires attached to bars 172 and shaft 170. Bars 172 can extend radially from shaft 170 into cylindrical conduit 152 and tapered conduit 154. Bars 172 can extend near the interior wall of hopper 156 without contacting the interior wall. Bars 172 in tapered conduit 154 vary in length to accommodate the tapered inner wall of tapered conduit 154. Bars 172 are mounted on shaft 170 in different radial directions. In a preferred embodiment, the ends of the bars 172 define a double helix.

In the embodiment of Figs. 13A and 13B, the feed rod 160 includes ten bars. In this example, adjacent bars are spaced along shaft 170 at 0.125 inch intervals, and each bar is rotated 45 degrees from the adjacent bar, except for the last two bars in the part. lower shaft 170 that are rotated 22.5 degrees. The diameter of the bars can be the preferred agglomerate size, on the order of 0.63 to 1.9 mm (0.025 to 0.075 inches). The material of the bars can be stainless steel or other structurally rigid inert material that is resistant to corrosion, such as metal, ceramic, plastic, etc. The feed rod can be manufactured from a conductive or non-conductive material, depending on the morphology of the powder. Non-conductive materials such as ceramics, plastics, and elastomers can be metallized to provide a conductive outer surface. Too many rods will compact the powder with the rotation of the rod, while too few rods will not support the double helix configuration. The spacing between the bars and the angle between adjacent bars can be inversely proportional to the number of bars used.

As noted above, feed rod 160 includes wires attached to rods 172. In the embodiment of FIGS. 13A and 13B, the wires define a double helix 174, a first chevron 176, and a second chevron 178. As shown, the double helix 174 includes a helix-shaped wire 174a at or near one end of each bar 172 and a helix-shaped wire 174b at or near the opposite end of each bar 172. Each helix wire 174a, 174b is directed downward from rod to rod in a clockwise direction as viewed downward from rod actuator 162.

The first chevron 176 may include a first chevron-shaped wire 176a attached to the bars 172 at a first spacing from the shaft 170, and the second chevron 178 may include a second chevron-shaped wire 178a attached to the bars 172 at a second spacing from shaft 170. First chevron wire 176a passes through hole 176b in shaft 170, and second chevron wire 178a passes through hole 178b in shaft 170. It should be understood that the helix-shaped wires and the chevron-shaped wires are not necessarily attached to each bar of the feed rod 160. In particular, the first chevron-shaped wire 176a is attached to the first bar (the uppermost bar) and to the fifth bar. The second chevron-shaped wire 178a is attached to the third bar and the seventh bar. The first and second chevrons can be 90 ° apart from each other.

ES 2 332 292 T3

In the embodiment of Figs. 13A and 13B, the helix-shaped wires and the chevron-shaped wires are threaded into holes in the respective bars and are coupled at each end. The helix-shaped wires are located at or near the ends of the bars, and the chevron-shaped wires are located at desired distances from the shaft 170. The holes in the bars 172 can be tool drilled, laser drilled, or drilled by electrical discharge machining (EDM). In a preferred embodiment, the holes in the bars 172 are edm drilled at angles that avoid significant bending of the wires. Therefore, the holes in each bar are roughly aligned with the adjacent bars. This arrangement allows the wires to slide through the holes more or less freely so that the powder loading forces are distributed along the entire length of the wires, thereby reducing the stress concentration. on the wires that could cause breakage. In other embodiments, the wires can be attached to the bars by laser welding, for example. In this example, the helix wires and the chevron wires have a diameter of 0.2 mm (0.008 inches).

The double helix 174 can be formed by joining the outer ends of the helically mounted bars 172 with the helix-shaped wires 174a and 174b. Looping the bars 172 to the wires at both outer ends creates a double helix wire pattern. The double helix wire pattern performs three main functions. First, the perimeter wire prevents the compressed powder from adhering to the conduit walls, particularly the walls of tapered conduit 154. Second, when the rod 160 rotates clockwise (facing down from the drive shaft), the double helix raises the powder up to the contact surface of the conduit wall and further reduces it to the preferred agglomerate flow size range. Third, when rod 160 rotates counterclockwise, the double helix pulls bulk powder down along shaft 170, as well as along free chevron-shaped wire paths. , into the dispensing nozzle 158. In addition, this rotary bulk powder feeding operation tends to break up compressed powder discs that are formed horizontally between the rotating bars 172.

The feed rod 160 uses a helical three-dimensional structure that includes the shaft 170 as a central support, the bars 172 as structural cross elements that form a helical pattern with a tapered bottom end geometry in a conical shape, and the wires that form the double helix 174 and first and second chevrons 176 and 178, as described above. The inverted conical shape allows the bars to transition from a larger diameter conduit to a smaller diameter powder discharge nozzle. The wires are attached to the bars to reduce the compression effects of the bulk powder and to promote the flow of the agglomerate slurry. The feed rod 160 can convey highly cohesive powder with microgram dispensing precision, while controlling the compaction tendency of the bulk powder. The compaction of the powder causes a blockage by the compression of the powder and this causes a jam in the dispensing. The helical three-dimensional structure provides an optimal bulk powder conveying element that can accurately transport and dispense all types of powder morphologies from easily flowable to highly cohesive. This ability is achieved by allowing only a small portion of the helical mechanical forces to be directed downward into the bed of bulk powder, thereby controlling compression effects appropriately for the individual characteristics of the powder being dispensed. Due to this compression control, it is possible to transport cohesive powder from a large diameter conduit to a smaller diameter conduit in an efficient manner.

Shaft 170 forms the central drive shaft of feed rod 160. Shaft 170 supports rods 172, double helix 174, and first and second chevrons 176 and 178 which, in turn, carry the bulk powder for precise dispensing. The central drive shaft allows the fine powder to flow along its smooth surface into the dispensing nozzle 158.

Bars 172 are cross-sectional structural elements that break up the compacted powder agglomerate bed. The bars 172 also support the helix-shaped and chevron-shaped wires. In addition, the bars 172 provide the helical scroll mechanism necessary to transport the bulk powder bed in a controlled, low-compression manner.

The chevron-shaped wires 176a and 178a provide cutting patterns in the bulk powder bed. The wires are positioned to reduce compacted powder and to open a temporary free path in the powder bed that allows small amounts of powder agglomerates to flow down through the powder bed under the action of gravity. In addition, the chevron-shaped wires cut through the bulk powder disk that forms between the bars 172. These discs are created by progressive compaction forces and form suspended structures of agglomerated powder. By cutting the discs, preferably in half, the discs become structurally unstable and begin to crumble and flow downward under the mechanical forces of the helically arranged rods 172.

Discharge element 166 (FIG. 12) is contoured and positioned to crumble a powder compression disk located in dispensing nozzle 158. The powder disk is formed when the feed valve 180 is closed and the wand 160 performs conditioning and raking operations of the bulk powder. Without the discharge element 166 to start and shrink the disc, the disc would jam the nozzle or fall into the cartridge when the valve is opened, likely causing overfilling of the cartridge. The dust disk has a great tendency to block the nozzle when the ambient humidity is above 50 percent.

ES 2 332 292 T3

Embodiments of discharge element 166 are shown in FIGS. 13A and 13B, 14A to 14F and 15A to 15D. Each of the embodiments uses the helical three-dimensional structure of bars and wires described above, but uses different discharge elements. The powder is dropped into the powder bed preparation zone 156a by rotating the helical three-dimensional structure described above. The outer helical wires break the attractive forces between the powder and the cylindrical conduit wall, and lift and aerate the powder bed when they rotate in the opposite direction. The chevron-shaped wires cut and further reduce the powder bed as the helical three-dimensional structure rotates. The powder bed preparation zone 156a improves the fluidity of the powder bed as it enters the tapered passage of the powder bed compression zone 156b. The flowability of the powder is enhanced by the ability of the helical three-dimensional structure to form natural agglomerates that allow the powder to flow when induced by the forces of the helical three-dimensional structure. In the powder bed compression zone 156b, the agglomerated powder bed undergoes compression due to the reduction in volume of the tapered conduit. The compression zone constantly increases the consolidation of the powder bed, while the bars and wires continue to reduce and aerate the powder bed. In discharge zone 156c, clumps of powder agglomerates are further reduced and discharged through nozzle 158. The discharge element controls the reduction and dispensing characteristics of the powder. An improper dust reduction control causes the discharge port to clog. An inadequate dust reduction control also prevents dispensing of the powder within a specified time limit without overdosing. The discharge element determines the final powder dispensing rate and the consistency of the powder agglomerates.

In the embodiment of figs. 13A and 13B, the discharge element 166 is configured as a modified bar 181. The two sides 181a and 181b of the modified rod 181 extend downward in a half helix that rotates counterclockwise, thereby forming a double helix. The modified double helix bar 181 and double helix 174 have opposite slopes. In other embodiments, one side of the modified bar is turned upward in a helical shape. The modified bar can be used as a clockwise or counterclockwise helix. In some embodiments, the modified stick can be constructed in an inverted U-shape or an S-shape. The U-shape works best for free-flowing powder, while the S-shape works best for cohesive powder. In the U-shape, both sides of the modified bar are turned toward the dispensing nozzle. In the S-shape, one side of the modified bar is turned toward the dispensing nozzle and the other side is turned up.

The modified double helix bar 181 of FIGS. 13A and 13B function as a rotatable biasing element at the lower end of the tapered conduit. Modified rod reverse tilt geometry adds lift and aeration to powder to control powder dispensing and improve powder consistency. The reverse tilt geometry also directs dust into the nozzle during the rake cycle. This creates an initial 2 to 4 milligram powder drop at the beginning of the dispense cycle and allows a longer fill time at the end.

Another embodiment of feed rod 160 is shown in FIGS. 14A to 14F. In the embodiment of Figs. 14A to 14F, the discharge member 166 is implemented as a cylindrical pin 183 mounted on the shaft 170 by a support member 185 having an inverted U shape. In the embodiment of Figs. 14A through 14F, an optional multi-slot deflector disk 189 may be located on top of tapered conduit 154 and attached to lower housing section 150a.

The powder dispensing module 54 54 further includes an orifice element 187 mounted to the lower end of the tapered conduit 154. The orifice element 187 may have one or more slot-shaped holes. In an embodiment shown in FIG. 14D, a craft element 187a includes two slot-shaped holes that intersect to form a cross. In other embodiments, the hole elements 187b and 187c include three intersecting slot-shaped holes, as shown in FIGS. 14E and 14F. The holes can be relatively wide, as shown in fig. 14E, or relatively narrow, as shown in FIG. 14F. Lead rod 160 is positioned such that cylindrical pin 183 is spaced from hole member 187 by a distance less than the natural agglomerate size. In operation, the cylindrical pin 183 rotates relative to the orifice element 187, causing the powder to be discharged through the holes of the orifice element 187.

Deflector disk 189 can be used to control the advance rate of the powder bed and to further reduce powder agglomerates as they enter the tapered conduit. In the discharge zone 156c, the clumps of powder agglomerates are reduced and then extruded by the rotating cylindrical pin 183 through the holes of the orifice element 187. The mechanism including the support member 185, the cylindrical pin 183, and the orifice member 187 controls the reduction and dispensing characteristics of the powder. Improper dust reduction control causes discharge port to clog. An inadequate dust reduction control also prevents dispensing of the powder within a specified time limit without overdosing. Support member 185 and cylindrical pin 183 determine the final powder dispensing rate and the consistency of the powder agglomerates. The mechanism including support member 185, cylindrical pin 183, and orifice element 187 can be configured to provide optimal powder flow and agglomerate size for a particular powder morphology. Support member 185 travels through a perimeter notch in lower housing section 150a to self-center feed rod 160. The cylindrical pin 183 in combination with the orifice element 187 produces a dispensing of agglomerates of

ES 2 332 292 T3 low strength powder. Orifice element 187 provides consistency to powder agglomerates within a more precise agglomerate size range.

A further embodiment of feed rod 160 is illustrated in FIGS. 15A to 15D. Discharge element 166 is implemented as helical auger blades 240 and 242 attached to shaft 170. Each auger blade 240, 242 performs approximately one half turn around shaft 170. The axial length of auger blades 240 and 242 may be approximately half the axial length of tapered conduit 154. As shown, the feed rod of FIGS. 15A to 15D uses fewer rods than the embodiment of FIGS. 13A through 13B, and the helix-shaped wires and the chevron-shaped wires may be attached to the upper edges of the auger blades 240 and 242. Auger blades 240, 242 and double helix 174 may have opposite pitches.

The powder dispensing module 54 shown in FIGS. 15A through 15D further includes an orifice element 244 mounted to the lower end of tapered conduit 154. In the embodiment of FIGS. 15A to 15D, the orifice element 244 has an inverted conical shape and is provided with a plurality of holes 244a for discharge of powder through the nozzle 158. In addition, the lower edges of the auger blades 240 and 242 are sloped to accommodate the inverted tapered bore element 244. A bearing 246 mounted on the lower end of shaft 170 engages an opening in orifice element 244 and establishes a desired spacing between auger blades 240, 242 and orifice element 244. The bearing 246 can be a jewelry material, such as a ruby ​​or sapphire, that is not contaminating to the dispensed drug powder. In operation, the auger blades 240 and 242 rotate with respect to the orifice element 244, causing the powder to be discharged through the orifices of the orifice element 244. In other embodiments, the orifice element may be flat, as shown in FIGS. 14D through 14F, and the bottom edges of the auger blades 240 and 242 are flat to accommodate the orifice element.

This embodiment rotates opposite to the feed rods shown in FIGS. 13A to 13B and 14A to 14F. In the discharge zone 156c, the powder agglomerates are forced to flow through the reverse pitch auger blades and then extruded and granulated by the rotating auger tip through the orifices of the orifice element 244. The mechanism formed by the auger blades and the orifice element controls the reduction and dispensing characteristics of the powder. Improper dust reduction control causes discharge port to clog. An inadequate dust reduction control also prevents dispensing within a specified time limit without overdosing. The mechanism formed by auger blades 240, 242 and orifice element 244 can compensate for variability in the height of the powder bed fluidic head, thereby reducing the sensitivity of the dispensing process to head conditions. from the powder bed. The half-turn double helix of the auger blades isolates the vertical forces of the fluidic bed against the dust in the nozzle, thereby eliminating force vectors that tend to compact the dust in the nozzle. The mechanism formed by auger blades 240, 242 and orifice element 244 can be configured to provide optimal monotonic powder agglomerate sizes. The mechanism provides consistency to powder agglomerates within a more precise agglomerate size range. Bearing 246 provides support and alignment to the bit while maintaining a powder membrane thickness from bit to hole.

In some embodiments, the discharge element 166 is mounted in a hole in the tip of the shaft 170. In other embodiments, the discharge element 166 is implemented in a removable tip of the shaft 170. For example, a double helix discharge element it can be formed into a removable tip that is snapped into the end of shaft 170. The removable tip can be changed to allow for different powder morphologies.

The following description of the operation of the powder dispenser module 54 refers to raking operations and dispensing operations for the embodiments of FIGS. 13A and 13B and 14A to 14F. Raking is an operation to prepare and recondition a bed of powder in a uniformly aerated matrix of preferred agglomerate size, thereby providing better flow characteristics for the transport of bulk powder. The preferred agglomerate size is the stable and natural size of the cohesive powder agglomerates created by a powder bed tumbling operation and is typically in a range of 0.63 to 1.9 mm (0.025 to 0.075 inches) of spherical diameter. Raking the powder bed can be done in the up mode or in the down feed mode. However, cohesive powder prefers upward raking for optimal aeration and improved flowability. Dispensing is an operation for conveying dry bulk powder in a spray-like manner, falling under the force of gravity without compression, such as a matrix of preferred agglomerates, discharging from a dispensing powder nozzle into a cartridge. The powder detection and dispensing apparatus described herein can operate with powder agglomerates in a range of 0.13 to 1.9 mm (0.005 to 0.075 inches) in spherical diameter, but is not limited to this range.

Feed rod 160 rotates clockwise as viewed from the top of dispensing module 54 to rake, condition, and aerate the bed of bulk powder. The clockwise rotation raises the dust due to an upward flux vector created by the double helix. In this operation, the rod can be seen as a screw, arranged vertically caught by the head, rotating towards the interior of the powder. The double helix rubs the walls of the conduit and also displaces the outer agglomerates towards the center of the dispensing hopper. As the rod rotates, the bars cause the large agglomerates to crumble evenly. This aerates the bed of bulk powder, creating a better consistency in the bed.

ES 2 332 292 T3

To dispense the powder, the wand 160 preferably rotates counterclockwise. Bars 172 and chevrons 176, 178 break up the powder bed and open a free path for the powder to flow along shaft 170. Double helix 174 adds a downward compression vector to drive the powder down and through dispensing nozzle 158. In other embodiments, the wand 160 rotates clockwise to dispense the powder.

However, agglomerates tend to be larger and the tendency for overfilling is much greater for powder dispensing by clockwise rotation.

In the embodiments described above, the helix-shaped rods and wires have a clockwise configuration as viewed from the top. It should be understood that the arrangement of the bars and wires of the feed rod may be reversed within the scope of the invention. Therefore, the helix-shaped rods and wires can have an anti-clockwise configuration as viewed from the top. In this configuration, the wand preferably rotates clockwise to dispense the powder.

The following description of the operation of the powder dispensing module 54 refers to raking operations and dispensing operations for the embodiments of FIGS. 15A to 15D. The feed rod 160 is rotated counterclockwise as viewed from the top of the dispensing module 54 to condition the bed of bulk powder and fill the auger. The double helix 174 adds a downward compression vector to draw the powder down and into the dispensing nozzle 158. At the same time, the auger blades 240, 242 supply upward force vectors to the powder to cause the powder in the auger to rise to the upper bed for aeration.

To dispense the powder, the feed rod 160 preferably rotates in a clockwise direction. Clockwise rotation lifts the powder from the upper bed due to an upward flow vector created by the double helix of the helical three-dimensional structure. In this operation, the upper rod can be seen as a screw, arranged vertically caught by the head, rotating towards the interior of the powder. The double helix rubs the walls of the conduit and also displaces the outer agglomerates towards the center of the dispensing hopper. As the rod rotates, the bars cause the large agglomerates to crumble evenly. This aerates the bed of bulk powder, creating a better consistency in the bed. Bars 172 and chevrons 176, 178 break up the dust bed and open a free path for the dust to flow along the shaft 170.

When dispensing is started, the powder from the auger is passed through the nozzle by the downward force vectors of the auger. During dispensing, additional powder is supplied due to aerated powder falling from the upper bed.

In the embodiment described above, the helix-shaped rods and wires have a clockwise configuration as viewed from the top. It should be understood that the arrangement of the bars and wires of the feed rod may be reversed within the scope of the invention. Therefore, the helix-shaped rods and wires can have an anti-clockwise configuration as viewed from the top. In this configuration, the wand preferably rotates counterclockwise to dispense powder.

In fig. 17 shows a block diagram of a controller for a single powder dispensing module 54 and corresponding sensing cell 114. Preferably, the powder dispensing controls provide redundant computing power, at the lowest level, strategically concentrated. The powder dispensing module 54 includes a dispensing controller 200 (FIG. 17) on a circuit board 184 (FIG. 11). Dispensing controller 200 may include three processors. A processor is provided for the rod actuator 162 and for the valve actuator 182, and a processor is used to control the control status LEDs 224 and the optional analog detector inputs. A control processor 210 is located on a rear panel of the detection module 34 as will be described later. The system uses a control processor 210 for each dispensing module 54 and its associated sensing cell 114. Processor 210 controls communications between sensing module 34 and dispensing module 54, as well as external communication. When fill parameters and a "start" command are provided, the control processor 210 provides the intelligence to read the sensing cell and commands the dispensing module actuators to fill the cartridges. Control processor 210 further communicates with supervisory processor 212 through a network interface. Supervisory processor 212 provides high-level control of all powder dispensing modules and sensing cells.

The controller in fig. 17, except for the monitoring processor, is repeated for each dispensing module 54 and associated detection cell 114 of the system. In the above example of a 6x8 array of dispensing modules, the system includes 48 controllers. This arrangement provides individual control and monitors the dispensing of powder in each cartridge.

In one embodiment, the powder dispensing module 54 is configured and controlled to accurately dispense 10.0 mg (milligrams) of powder in ten seconds. Average flow rate is 1.0 mg per second at precision

ES 2 332 292 T3 of +/- 0.3 mg, or 3 percent. The control circuit makes at least 20 decisions per second for filling at this flow rate. In other embodiments, the control circuit makes more than 20 or less than 20 decisions per second to achieve a desired accuracy. The geometry of the feed rod provides sufficient flow consistency to achieve this performance. The feed wand splits powder clumps into small agglomerate particles. Mechanically fed agglomerate slurry exhibits flow characteristics that allow the powder to stop when the feed wand stops, with minimal powder spillage, causing overfilling of the cartridge.

The control circuit can provide the following controls and functions.

1. The speed of the rod can vary from 0.1 revolutions per second to 5 revolutions per second at 50 different speeds.

2. The rod can be shaken during filling. During shaking, the rod rotates alternately clockwise and then counterclockwise, such as, for example, with a two-step forward / one step forward type of movement. back based on a programmable stirring factor. A "shake under weight" function performs the shake motion when the fill weight is less than a selected weight. A "shake over weight" function performs the shake motion when the fill weight is greater than the selected weight. A "stir between" function performs the shake motion when the fill weight is between two selected weights. A stirring index is the selected rotation speed during stirring. A stirring weight is the weight selected to start or stop stirring, and a minimum stirring time can be selected when the selected stirring weight is reached. Agitation may not be used in some applications.

3. The control circuit can open and close the powder dispensing fill valve.

Four. The control circuit can zero the sensing cell and start a powder dispensing cycle, and it can stop the powder dispensing cycle.

5. The control circuit can rake the powder into the powder dispenser in a sequence defined by rake time, shake time, and speed.

6. A new charging function initiates a raking / shaking cycle that normally takes place after charging the Dispense Module with new powder. Rake time, agitation time and speed are specified.

7. Additional features include automatically opening and closing the fill valve during a fill cycle, automatically raking the powder each time the valve is closed, and automatically stirring the powder after raking each time the valve is closed.

8. A “stop steps” function sets the number of steps to reverse the rotation of the feed rod after reaching a target weight. This tends to reverse the flow of powder to prevent overfilling and is dependent on the type of powder morphology and relevant ambient humidity conditions.

9. A speed control feature forces the feed wand to move at full speed until a selected fill weight is reached. At this trigger point, the proportional control begins to slow down the rod in proportion to the target weight minus the actual weight. This approach reduces the total fill time. For a nominal fill weight of 10 mg and a tolerance of +/- 3 percent, any fill weight between 10.3 and 9.7 mg is acceptable. Since an overfilled cartridge must be discarded, the filling stops as soon as possible after the minimum weight is reached to avoid possible overfills. The minimum weight is set, for example, at 9.75 mg, which is slightly above the actual lower limit of 9.7 mg. This is necessary as when the powder falls into the cartridge, peripheral forces such as inertia, aerodynamic forces, static force, and magnetic field flux can cause temporary weight readings that are slightly higher than the actual weight of the powder. The reading provides the actual weight for a short time of a few tenths of a second. Setting the minimum weight to 0.05 mg above the true lower limit reduces the risk of an underfilled cartridge.

10. The parameters associated with the fill cycle include the proportional gain of the fill servo loop, the integral gain of the fill servo that is activated, for example, at 10 mg below the target weight, and the maximum rod speed allowed during a cycle filling. Rod speed can be controlled by specifying a speed index between 0 and 50. The rod speed in revolutions per minute as a function of the rod speed index has the characteristic that it is relatively linear for low values ​​of the rod speed index and then increases radically at the maximum rod speed. This feature provides more precise control at lower speeds than at higher speeds and allows the wand to move faster during the initial 70 percent of the fill cycle to quickly fill the cartridge to 90 percent of its fill weight. . The maximum speed of the rod is normally about 5 revolutions per second. Beyond that speed there is a risk that the powder will become so compact that the dispenser must be removed and cleaned to restore the initial characteristics of the powder flow.

ES 2 332 292 T3

An agitation factor controls the reciprocating movement of the feed rod as it rotates, if agitation is allowed. In this embodiment, the ratio of forward rotation to reverse rotation is two. Therefore, the feed rod rotates 2n steps forward and n steps backward, based on the value of the stirring factor. Thus, for example, a shake factor of 500 represents 1000 steps forward and 500 steps back, while a shake factor of 1 represents 2 steps forward and 1 step back. In other embodiments, the ratio of forward rotation to reverse rotation may have a value other than two and / or may be programmed.

eleven. A fill time servo control function adjusts the maximum rate of the wand speed in proportion to the time it has been at full speed during the last fill cycle. The time it has been at full speed is a good indication of the fluidity level of the powder. If the actual time at maximum speed is greater than that set, then the controller increases the maximum speed index of the wand to speed up filling. On the contrary, if the real time at maximum speed is less than the established time, the maximum speed index of the rod is decreased to maintain a constant process time. Although filling as quickly as possible seems desirable, there is a risk of compacting the powder, clogging the dispensers, or overfilling the cartridges.

The parameters of the powder dispensing module 54 are interrelated as follows. Greater control of overfilling is available when smaller sizes of particle agglomerates are dispensed into the cartridge. Accelerating the rod increases the flow rates but the powder is compressed into large agglomerates. Large agglomerates increase flow but are more prone to overfilling in the last few seconds of filling. A large powder bin saves loading time at the dispenser, but compresses the powder into large agglomerates and requires more conditioning of the powder prior to filling. Agitation breaks up large agglomerates for more accurate filling, but reduces flow rate. Conditioning the powder prior to filling increases the consistency of the fill, but increases the overall fill time.

One embodiment of the cartridge filling cycle is described with reference to Figs. 18 and 19. The fill cycle is described with reference to an example of filling cartridges with a 10 mg dose of Technosphere microparticles in 10 seconds. It should be understood that different parameters can be used for different fill weights, different powder morphologies, different fill times, and different environmental conditions. The cartridge fill cycle can be executed by control processor 210 and dispenser controller 200.

The dispenser control processors, together with the monitoring computer, contrast all these control factors with the fill weight values, read 20 times per second, while the dispensers fill the cartridges. These data, when compared to ideal dispensing cycles, provide feedback for improved powder consistency, flowability, and cohesion, drug efficacy on patients, and overall quality control. It should be understood that weight-related values ​​can be read more than 20 times or less than 20 times per second within the scope of the invention.

Referring to fig. 18, the control parameters for the operation of the dispensing module can be set in step 250. For example, initially, agitation is disabled. The valve control parameters can be set so that raking is carried out for two seconds after a new powder load, the speed index is set to 44, automatic opening is activated and a automatic raking after closing. Fill parameters can include 8.8mg setting, in which proportional control is started, target fill weight can be set to 10.0mg, proportional gain can be set to 1.0, integral gain can set to 0.03, and the maximum rod speed index can be set to 41 (two revolutions per second). The agitation factor can be set to 50, and the fill time servo control can be set to 10.0 seconds. A bipolar ionizer can be activated to charge and neutralize the powder dispensing module and cartridge.

In step 254, the dispensing hopper 156 is filled with powder by operation of the powder transport system 32. The powder is supplied to the die block 50 by the powder aerator 72. The powder is supplied through the channels of the die block 50 to each of the powder dispensing modules 54. When the excess powder passes through the die block 50 and is detected by the dispensing fill level sensor of the suction manifold 84, the loading of the dispensing modules 54 ends and the powder transport system is deactivated. The dispensing hopper 156 can be raked during the hopper fill cycle to remove large air gaps and inconsistencies in the powder bed.

The hopper assembly 74 is filled by the operator or by another automatic injection system. The flow assist mechanism rotates to break up the new compressed powder. The agglomeration rollers rotate to supply powder in large agglomerates to the aerator dump valve 72. A dump valve level sensor indicates that the dump valve is full to stop the agglomerate rollers. Blower assembly 70 rotates at approximately 3500 rpm to circulate gas throughout the system. The air broom rotates in preparation for the powder supply through the dump valve. The bypass valve is set at 50% to facilitate the transport of draft gas and dust.

ES 2 332 292 T3

The dump valve rotates in 10 degree increments per second to gradually supply powder to the air broom chambers. As the powder becomes available to the air broom, the small agglomerates rise through risers into the dispenser fill chamber. At this point, much of the filling occurs in the last positions of the dispensers. After the dump valve cycle is complete, the bypass valve rotates for a 0% percent bypass in 10 degree per second increments to gradually establish maximum air broom pressure. This transports all but the heaviest agglomerates into the dispensing chamber and fills the center rows of the dispensing modules. Finally, blower assembly 70 increases speed to 8000 rpm to transport the remainder of the powder from the air broom chamber to the first rows of the dispensing modules.

As these fill cycles continue, the dispensing hoppers fill. The blower assembly 70 in combination with the bypass valve equalizes the height of the dispensing bed through the dispensing modules by removing dust from high peaks, circulating fine dust through the system, and depositing dust in low areas. powder bed pressure between peaks.

In step 258, a cartridge is placed under the dispensing nozzle 158 and over the weight sensing cell. As described above, a cartridge tray is positioned between the array of powder dispensing modules 54 and the detection module 34. In step 260, the cartridge is filled with the prescribed dose of powder. The filling cycle will be described later with reference to FIG. 19. In step 262, the fill valve is closed and rotation of the feed rod is stopped.

At step 264, a determination is made as to whether the dispensing hopper needs to be refilled. If the dispensing hopper needs to be refilled, the process returns to step 254. If the dispensing hopper does not need to be refilled, the process returns to step 256. In the present example, the dispensing hopper can be refilled after four doses of 10 , 0 mg. It should be understood that the filling of the dispensing hopper may start after more than four or after less than four cartridge fill cycles, depending for example on the capacity of the dispensing hopper and the amount of powder dispensed in each cycle. filling. The dispensing hopper is refilled in step 254. If refilling is not required, the process proceeds with the fill cycle for the next cartridge in step 256. In the present example, the dispensing hopper contains a quantity of powder sufficient for twenty doses of 10.0 mg. In some embodiments, the filling process is dependent on the height of the powder in the dispensing hopper to create a fluidic head of dry powder and to aid gravity-induced powder flow. Without a proper fluidic head, the fill time increases beyond the fill time limit. Other techniques can be used to determine if refilling of the dispensing hopper 156 is required. For example, if a very small amount is dispensed or no amount of powder is dispensed during the cartridge fill cycle, it can be assumed that refilling of the dispensing hopper 156 is required.

One embodiment of the cartridge fill cycle is shown in fig. 19. An initial operation is to zero the detection cell in step 280. The zeroing operation subtracts the weight of the empty cartridge from the detection cell reading so that the detection cell reads zero or near zero. at the beginning of the fill cycle. The control circuit waits 0.5 seconds for the sensing cell to complete its zeroing cycle and continues with the fill operation if the sensing cell reads less than 0.02 mg. Otherwise, the reset cycle is repeated.

In step 282, fill valve 180 is opened. As will be described later, the fill valve opening may be slightly offset from the dispensing nozzle 158 to ensure consistent operation.

At step 284, the feed rod rotates counterclockwise for filling. Typically, actual fill begins after about 2 seconds, the time required to convey enough powder to restart powder flow after raking. Initially, the feed wand rotates at the maximum speed specified during dispensing module setup. The height of the powder dispensed into the cartridge is monitored during filling.

At step 286, a determination is made whether the current sensed weight is greater than the selected weight at which proportional control is initiated. In the example of a 10 mg dose, the selected weight can be 8.8 mg. If the detected weight is not greater than the selected weight, the process returns to step 284 and the rotation of the feed rod continues at maximum speed. If the sensed weight is greater than the selected weight, the rod speed servo control is used in step 288. An initial error is determined as the target weight minus the selected weight at which the servo control starts. In the example above, the initial error is 10.0 - 8.8 = 1.2 mg. Rod speed is controlled as follows:

new rod speed index = ((current error / initial error) * proportional gain * maximum index) + (integral gain * elapsed time).

In this embodiment, the control circuit sets the rod speed based on the current error 20 times per second. The current error is determined as the target weight minus the current detected weight. For a current error of 0.6 mg, which is half the initial error in the example above, the rod speed is reduced from the index

ES 2 332 292 T3 maximum of 41 up to an index of 20. Due to the non-linearity of the index-speed curve, the actual speed of the rod is less than half the initial speed. As noted above, the index-velocity curve is linear to zero, where much of the control is needed. The proportional gain value allows the amount of speed change to be varied depending on the error. Elapsed time is activated when the current detected weight is greater than the target weight minus 1.0 mg. The proportional error equation reduces the speed of the rod based on a fixed ratio of the actual weight to the desired weight. There are moments of very low speed, when the target weight is close, when the speed of the wand is not adequate to produce a flow of powder. If left unchecked, the fill cycle would run for too long and the target weight could not be obtained. The integral gain factor increases speed by accumulating the elapsed time and multiplying the elapsed time by the integral gain factor. This factor increases the new speed of the wand and forces the wand to rotate faster to overcome the loss of fill speed.

Referring back to FIG. 19, the current sensed weight is compared to the minimum weight in step 290. If the current sensed weight is less than the minimum weight, the servo control of the rod speed continues at step 288. If the current sensed weight is equal or greater than the minimum weight, the current detected weight is compared to the maximum weight in step 292. If the current sensed weight is greater than the maximum weight, it is determined in step 294 that the cartridge has been overfilled. If the current sensed weight is not greater than the maximum weight, the fill cycle ends and the process returns to step 262 of FIG. 18.

In step 262, the control circuit can adjust the servo control. If the fill time was longer than 11 seconds, the control circuit can increase the maximum speed rating by one. If the fill time was less than nine seconds, then the control circuit can decrease the maximum speed rating by one. This control tries to maintain a constant fill time of 10 seconds.

Preferably, valve member 190 is positioned such that valve opening 191 is offset from the lower end of tapered conduit 154 when fill valve 180 is in the open position. More particularly, valve member 190 is offset such that valve opening 191 is posterior to tapered conduit 154. Therefore, the valve opening 191 is displaced towards the closed position of the valve. In addition, valve member 190 rotates in one direction during valve opening and closing to compensate for any hysteresis in the drive train. Thus, for example, the valve member 190 may rotate clockwise to open the valve and may further rotate clockwise to close the valve. This operation reduces the risk of non-constant fill or overfill that can result from uncontrolled displacement between valve member 190 and tapered conduit passage 154 in the open position.

Any displacement between valve opening 191 and tapered conduit 154 in the open position produces a small shelf on top of valve member 190 that can accumulate dust. If the valve opening 191 is in an advanced position relative to the tapered conduit 154, any amount of powder on the shelf is ejected when the valve is closed, thereby possibly overfilling the cartridge. When valve opening 191 is in a posterior position relative to tapered conduit 154, the valve closes without expelling any amount of powder from the shelf. The powder is ejected when the valve is opened for the next cartridge, and the ejected powder is measured by the detection cell.

The powder dispensing module 54 and its operation have been described in connection with embodiments for dispensing a specific amount of Technosphere microparticles in a specified time. It should be understood that a variety of different dispensing module structures and operating protocols can be used in the present invention. For example, the feed rod may use different structures, such as different bar configurations, different wire configurations, and in some embodiments no wires may be required. Different numbers of helix-shaped wires and chevron-shaped wires can be used. Different download elements can be used. The feed wand can use a different feed mechanism, such as a screw mechanism, to dispense the powder. Any suitable fill valve mechanism can be used to control the dispensing of the powder. As far as operation is concerned, any operating protocol that achieves desired operating parameters can be used. For example, any suitable movement of the feed rod can be used, such as rotation, reciprocating, or vibration. The speed of movement can be fixed or variable, or a combination thereof. Agitation, proportional control, integral control and other control techniques can be used separately or in combination as required. The sensing module can be configured to provide sensed values ​​at any desired rate within the capabilities of the sensing module. In general, the powder dispensing module 54 should have a compact structure to allow its mounting in a die as described above and should be configured to dispense a desired amount of powder in a specified time interval in response to a control circuit that receives sensed values ​​from a sensing module, such as the weight detector in the embodiment described above.

As shown in figs. 20 and 21, detection module 34 may include detection assemblies 110 mounted in detection housing 100. In the illustrated embodiment, each detection assembly 110 includes two detection cells 114. The sensing assemblies 110 are mounted in the sensing housing 100 so that the sensing cells 114 are positioned to weigh the cartridges 20 in the cartridge tray 22. In one embodiment, the detection cells 114 are mounted in a 6x8 array on 2.54 cm (one inch) centers.

ES 2 332 292 T3

In this embodiment, 24 detection sets 110, each including two detection cells 114, are used to provide an array of 48 detection cells.

Each detection assembly 110 has a vertical configuration in which two detection cells are packed together. The weight sensing mechanical components are located at the top of the assembly, the electronic circuitry is located below the mechanical components, and an electrical connector 300 is located at the bottom of the sensing assembly 110.

The detection housing 100 includes a detector positioning plate 310, a detector housing 312, a detector tray 314, and a guide pin assembly 316. The positioning plate 310 includes a matrix of apertures that coincide with the positions of the cartridges 20 in the cartridge tray 22 so that the sensing cells 114 are precisely positioned relative to the cartridges 20. The guide pin assembly 316 allows the positioning plate 310 to be positioned over the sensing assemblies 110 without damaging the sensing probes 112 or sensing cells. Detector tray 314 may include an arrangement of dividers to position detection assemblies 110 in detection module 34.

The sensing module 34 further includes rear sensing panels 330 having connectors 332 to mate with the electrical connectors 300 of the sensing assemblies 110. In the embodiment of Figs. 20 and 21, the detection module 34 includes two rear panels 330, each presenting 12 connectors 332 to accommodate a total of 24 detection assemblies 110. Each rear sensing panel 330 may include control circuitry to process signals from sensing assemblies 110 and to communicate with powder dispensing modules 54 during cartridge filling operations.

The detection module 34 may be provided with an arrangement for cooling the detection assemblies 110, including a detector cooling rack 340, a detector cooling housing 342, and detector cooling manifolds 344 and 346. The cooling air can be directed through the cooling manifolds 344 such that forced air cooling is provided to the lower portion of the sensing module 34, which contains the electrical circuitry. In the embodiment of Figs. 20 and 21, the cooling manifolds 344 are coupled to the detector tray 314 and the cooling manifolds 346 are coupled to the cooling housing 342. With this arrangement, the cooling air flows into the sensing module 34 through the cooling manifolds 344, circulates through the detector tray 314, and then descends into the cooling housing 342 and is expelled through through the cooling manifolds 346. In another cooling arrangement, cooling manifolds 346 are coupled to detector tray 314 such that cooling air is directed through detector tray 314. Unused openings in detector tray 314 can be closed by cover plates 348. Each of the cooling manifolds 344 and 346 may include internal passages that provide a uniform flow of air through the sensing module. In addition, the cooling manifolds 344 and 346 may include temperature sensing elements to monitor the temperature of the sensing module.

A first embodiment of the weight sensing probe that provides an interface between the weight sensing cell and the cartridge 20 is shown in FIG. 22. Probe 112 includes a main body 360 that includes a post 362 that is hooked to the sensing cell, a head 364, and a cup-shaped receptacle 366 that collects dirt and dust particles from the tray. Probe 112 further includes a dirt skirt 370 that deflects dirt and dust particles away from the sensing cell and pins 372 to engage and support a cartridge 20. The three pins 372 are spaced equidistantly at 120 degree intervals and They are designed to flex elastically and then return to their original positions. Additionally, the pins are designed to sag in an overload condition to protect the sensing cell. In the embodiment of fig. 22, the pins 72 are removable for changes in the height of the pins for different designs of the cartridge tray. The small cross-sectional area of ​​the pins reduces the aerodynamic effects of thermal currents that can add thrust load forces to accurate microgram weight measurements.

A second embodiment of the weight sensing probe that provides an interface between the weight sensing cell and a cartridge 20 is shown in FIG. 23. A probe 112a includes a main body 380, which includes a post 382, ​​a head 384, and a cup 386. The cup 386 collects dirt and dust particles from the tray. A dirt skirt 390 diverts dirt and dust particles away from the detection cell. In the embodiment of fig. 23, probe 112a includes pins 392 that are integrally formed with head 384. Each of pins 392 is reinforced with a radial reinforcing plate. This configuration adds structural rigidity to the vertically vocalized tenons. This configuration also reduces vibration and drift at the tips of the tenons, thereby damping the tuning fork effect.

A first embodiment of the dust aerator 72 is shown in FIGS. 24 to 27 and 28A to 28C. A second embodiment of the dust aerator 72 is shown in FIGS. 29 to 32. The dust aerator 72 includes a manifold block 500 that defines a gas inlet 78, a dust inlet 80, and dust outlet ports 82. As described above, gas inlet 78 is connected via tube 76 to blower assembly 70, hopper assembly 74 is mounted to powder inlet 80, and powder outlet ports 82 are connected to respective channels of matrix block 50. The dust aerator 72 may include an air broom 510 to supply the dust through riser tubes 512 to the dust outlet ports 82 and a dump valve 520 to supply a quantity of dust to the air broom 510 from the inlet. 80 dust. In the realization of

ES 2 332 292 T3 FIGS. 24-27 and 28A-28C, four risers 512 in manifold block 500 connect air broom 510 to dust outlet ports 82. The dust aerator 72 further includes a transfer valve 524 that directs the transport gas received through the gas inlet 78 toward the air broom 510 and toward a bypass manifold 526 in a desired ratio. Transport gas directed through bypass manifold 526 is flowed through powder outlet ports 82 to die block 50 to transport the powder to powder dispensing modules 54 mounted in each channel of block 50. matrix.

The air broom 510 includes a generally cylindrical aeration tube 530 having a hollow interior and which is provided with discharge nozzles 532. The aeration tube 530 is located on an inside diameter in the manifold block 500. The discharge nozzles 532 can be formed in a helical pattern in the aeration tube 530 and can be approximately tangential with respect to a cylindrical surface of the aeration tube 530. Dividers 534 are spaced along aeration tube 530 and define annular chambers 542 corresponding to respective riser tubes 512. In addition, air broom 510 includes blades 590 attached to dividers 534 and spaced around annular chambers 542. The combination of discharge nozzles 532 and blades 590 provides efficient transport of a powder slurry into the block. 50 matrix. A flow directing element 536 coupled to one end of the aeration tube 530 includes vanes to help break up dust clumps and direct the transport gas from the transfer valve 524 into the hollow interior of the aeration tube 530. An aeration core 538 is contoured to help equalize the flow of the transport gas through the discharge nozzles 532. A motor 540 causes aeration tube 530 and flow directing element 536 to rotate within manifold block 500. The motor 540 can have a variable speed and rotates the air broom 510 at a relatively high speed, for example 3500 rpm, to transport a powder slurry.

The dump valve 520 includes a cylindrical core 550 having diametrically opposed cavities 552. The core 550 is mounted on an inside diameter in the manifold block 500 above the air broom 510 and is connected to a motor 554 to rotate about its central axis. Core 550 is positioned by motor 554 with one of the cavities 552 facing upward toward the powder inlet 80. Powder is supplied by hopper assembly 74 through powder inlet 80 to fill or partially fill cavity 552. Then, core 550 rotates 180 ° causing powder to be conveyed into annular chambers 542 around the aeration tube 530. The maximum amount of powder delivered in a single operation of the dump valve 520 is defined by the volume of the cavity 552.

The bypass valve 524 includes a valve element 560 mounted on an inside diameter in the manifold block 500 and a valve actuator 562 for rotating the valve element 560 about its central axis. Valve element 560 may be configured as a hollow cylinder having an inlet port 564 and outlet ports 566 and 568 at selected circumferential positions. Ports 564, 566, and 568 may be provided with paddles to block and break up powder clumps. By proper adjustment of valve member 50, transport gas received through gas inlet 78 can travel in desired proportions through air broom 510 and through bypass manifold 526. In one embodiment, bypass valve 524 is adjusted during powder supply to die block 50. In another embodiment, bypass valve 524 is in a fixed position during powder supply to die block 50.

The powder aerator 72 may further include flow straighteners 570 and a contoured flow element 572 to help provide a uniform flow of transport gas through each of the powder outlet ports 82. Each outlet port 82 may be configured as a discharge cavity adapted to the inlet end of one of the channels 60a to 60h. Bypass manifold 526 supplies transport gas to the top of each discharge cavity, and each riser tube 512 draws aerated powder up into the transport gas flow in the discharge cavity, as best shown in Fig. fig. 28A.

Dust aerator 72 serves as the interface between hopper assembly 74, die block 50, and blower assembly 70. The dust aerator 72 receives fresh dust from the hopper assembly 74 and receives recirculated dust from the blower assembly 70. The fresh powder is received through the dump valve 520, and the recirculated powder is received through the gas inlet 78 and distributed through the transfer valve 524 to the air broom 510 and the bypass manifold 526 according to the bypass valve position 524.

The second embodiment of the dust aerator 72 shown in FIGS. 29 to 32 is similar to the dust aerator shown in Figs. 24 to 27 and 28A to 28C, except as follows. As best shown in Figs. 31 and 32, the air broom 510 similarly includes dividers 534a that are spaced along the aeration tube 530 and that define annular chambers corresponding to the respective risers in the manifold block 500. The air broom 510 of the second embodiment does not include spaced blades around the annular chambers. Furthermore, the dust aerator of FIGS. 29 to 32 is provided with a motor 540a that rotates the air broom 510 at a relatively low speed, for example 1 to 10 rpm, to transport powdered aerosol.

Dust aerator components 72 include air broom 510, dump valve 520, and bypass valve 524. In addition, bypass manifold 526, flow element 572, and flow straighteners 570 are used to equalize gas flow within each channel of die block 50. Air broom 510, bypass valve 524, and dump valve 520 are motor driven and controlled by a system control computer.

ES 2 332 292 T3

The bypass valve 524 channels the incoming transport gas in two directions: towards the bypass manifold 526 and towards the air broom 510. The rotary cylindrical valve has longitudinal grooves to channel flows while maintaining a relatively constant hydraulic loss, thus favoring a stable discharge.

The air broom 510 has several elements. The inlet channeling vanes of the flow direction element 536 change the direction of the incoming transport gas in an efficient and less lossy manner, while creating an impactor system that blocks and removes loose agglomerates before they clog the nozzles downstream 532 download. Tangential gas discharge nozzles 532, which preferably have a double helix configuration, are disposed along the length of aeration tube 530. The air broom 510 is divided into four annular chambers 542. Medication powder supplied from the dump valve 520 is aerated into annular chambers 542. Tangential discharge nozzles 532 effectively aerate and sweep the medicament powder from the chamber walls. The bypass valve 524 allows the two transport gas streams to be inversely controlled, that is, one can be increased while the other is decreased. This control function allows the drug powder to rotate within the annular chambers 542 to form the natural average agglomerate size. The transport gas flow can then be increased steadily to transport the aerated powder slurry up through riser tubes 512 into the channels of the die block 50, filling the channels of the die block at a controlled particle deposition process. This conveying process takes advantage of the unwanted powder morphology of naturally agglomerating powder and brings it to a bonded state where it can be conveyed effectively and pneumatically.

Riser tubes 512 cross the discharge cavity of each outlet port 82. At this time, the horizontal transport gas deflects the rising and emerging powder slurry down into the channels of the die block 50. This process creates the conditions for the controlled particle deposition process.

The dust aerator 72 receives a known quantity of dust from the hopper assembly 74. The dust is collected in the dump valve 520. The dump valve 520 isolates the transport gas from the hopper assembly 74. In addition, the dump valve 520 transfers the powder through this gas interlock to the air broom 510. The dump valve 520 may have an optional ability to make an approximate weight measurement of the initial amount of drug powder deposited into the system from the hopper assembly 74. Weight measurement can be performed by a load cell located in cavity 552 of dump valve 520. The rough weight measurement can be used as a feedback control for the hopper assembly 74 and also as data to monitor the dispensing rates of the bulk powder.

Air broom 510 fluidizes, disperses, and entrains drug powder into a transport gas in annular chambers 542. Tangential discharge nozzles 532, in a helical configuration, supply transport gas through chambers 542. The helical configuration may include one or more helixes, such as a double helix. In addition, the air broom 510 includes gas channeling vanes in the flow directing element 536 that effectively direct the gas into the aeration tube 530 and that act as impactors to reduce large agglomerates before they reach the discharge nozzles 532.

Bypass valve 524 divides incoming transport gas between air broom 510 and bypass manifold 526. Bypass valve 524 is configured to prevent any turbulent eddy flow conditions within a compact design. The valve features slotted flow ports to optimize and control gas flow. The transfer valve is used to control the transport of the agglomerated and aerated powder slurry into the channels 60a to 60h of the die block 50.

Contoured flow element 572 is located within bypass manifold 526 to improve the flow geometry of the conduit. When bypass gas flows from bypass valve 524 into bypass manifold 526, it is preferable to create isokinetic flow patterns to prevent the formation of turbulent flow or interrupted flow stagnation zone conditions.

The flow straighteners 570 include vanes that regulate the flow of gas by limiting and straightening the flow of gas as it is discharged into the discharge cavity 580. By altering the spacing between the blades, it is possible to achieve uniform flow rates through each of the channels 60a to 60h of the die block 50.

A first embodiment of the hopper assembly 74 is shown in FIGS. 33 and 34. As shown in figs. 33 and 34, the hopper assembly 74 includes a hopper body 600 that defines a powder reservoir 610, for storing a powder supply, and a powder outlet 612 that is coupled to the powder inlet 80 of the powder aerator 72. . The hopper assembly 74 may be provided with a hinged lid 614 and a flow assist mechanism 620. Flow assist mechanism 620 may include a helical coil 622 located within powder bin 610 and a motor 624 for rotating coil 622. Hopper assembly 74 may further include granulator 630 in a lower portion of powder bin 610. dust. The granulator 630 may include a first agglomeration roller 632 coupled to a first motor 634 and a second agglomeration roller 636 coupled to a second motor 638. Each of the agglomeration rollers 632 and 636 is provided with a plurality of pins 640 that extend radially from the respective roller. In one embodiment, the location of pins 640 on each of rollers 632 and 636

ES 2 332 292 T3 defines one or more helical patterns. In addition, the agglomeration rollers 632 and 636 may have hollow centers and may be provided with air holes connecting with the hollow centers. Gas connectors 650 at the ends of rollers 632 and 636 can be connected to a source of pressurized air. Air flow through the holes in rollers 632 and 636 helps aerate the powder that is being supplied to the system.

In operation, after the powder bin 610 has been filled to the level of the hopper level detector, the first and second agglomeration rollers 632 and 636 rotate causing agglomeration of the powder and discharging the agglomerated powder through the powder outlet 612 to powder aerator 72. In a preferred embodiment, the agglomeration rollers 632 and 636 rotate in opposite directions, with the tops of the rollers 632 and 636 rotating towards each other. However, the operation is not limited to this aspect. The agglomeration rollers 632 and 636 can rotate constantly, with a reciprocating motion or with a combination of a continuous motion and a reciprocating motion, and may be reversed. The rotation protocol depends on the morphology of the powder. The granulator 630 produces powder agglomerates in a desired size range to improve the flow of powder from the hopper assembly 74 into the powder aerator 72.

A second embodiment of the hopper assembly 74 is shown in FIGS. 35 and 36. The hopper assembly of FIGS. 35 and 36 is similar to the hopper assembly of FIGS. 33 and 34, except the following. In the hopper assembly of FIGS. 35 and 36 the flow assist mechanism is not used. Furthermore, the granulator 630 is implemented with agglomeration rollers 632a and 636a, each of which is provided with a plurality of separate discs 660 mounted on the shafts of the respective rollers. The disks 660 may be provided with notches 662 that help to move the powder down through the reservoir 610. The disks of the roller 632a may mesh with the disks of the roller 636a.

Bulk powder can be introduced into the powder container 610 through the opening in the top of the hopper body 600 with the lid 614 open. In the second embodiment of the hopper assembly 74 shown in FIGS. 35 and 36, a powder slurry may be introduced into the powder container 610 through a fitting 670 at an inclined portion of the hopper body 600. The fittings 672 mounted on the top of the hopper body 600 provide an outlet for the transport gas introduced through the fitting 670 with the powder slurry.

The hopper assembly 74 is the main powder reservoir and is the stage where the powder is introduced into the powder supply system 32. The hopper assembly 74 is designed for highly cohesive powders such as Technosphere microparticles. The 630 granulator produces powder agglomerates in a finite size range. This preconditioning improves the entrainment and aeration characteristics of the powder by creating a more uniform mix of agglomerated powder of various sizes. In addition, the powder granulation process aerates and mixes the powder that is normally compressed by gravity when it is piled up within the powder container 610.

In the central region of the powder reservoir 610, the flow assist mechanism 620 causes the powder to drift downward or fall into the granulator 630. The need for the flow assist mechanism 620 depends on the level of cohesion of the powder. The effect may become more apparent when the concentration of the drug is increased, such as an increase in protein content that makes the particles more viscous or sticky.

A first embodiment of the blower assembly 70 is shown in FIGS. 37 and 38. As shown in figs. 37 and 38, the components of the blower assembly 70 may include a variable speed blower 700 and a cyclone separator 702. The blower 700 includes a blower motor 704 supported by a motor bracket 706 and an impeller 708 mounted in a housing 710 of the blower. Blower housing 710 has a discharge port 712 for supplying transport gas through tube 76 to dust aerator 72. The adapted suction manifold 84 is mounted to the lower end of the blower housing 710. As described above, transport gas is recirculated from die block 50 to blower assembly 70. Suction manifold 84 includes inlet ports 714a, 714b, 714c, and 714d that are connected to respective channels of die block 50. The cyclone separator 702 includes a cylindrical suction manifold housing section 84a, which is mounted in the blower housing 710, and a cyclonic container 720 mounted below the suction manifold 84. The cyclone separator 702, which serves as a gas particle separation device, receives agglomerates of powder that pass through the die block 50 without being supplied to the powder dispensing modules 54.

A porous induction rod 724 is located in the center of the cyclone vessel 720 and is connected to a gas conditioning system 730, as shown in FIG. 41 and as will be described later. The gas conditioning system 730 supplies conditioned gas through the porous induction rod 724 to establish a precisely controlled relative humidity within the powder supply system 32.

In other embodiments, the conditioned gas may be blown through a valve into the closed loop system from a source such as a pure water value source or a steam source. Loop relative humidity is controlled by sensing gas in a small bypass loop that is connected to a sensing chamber for temperature, pressure, and relative humidity detectors. The bypass loop may be located between the blower discharge port 712 and the adapted suction manifold 84. In further embodiments, the driven valve system can be configured as a two-port system that allows an amount of conditioned gas to be pushed into the closed loop system, and an identical or compensatory amount of transport gas to be discharged outside. closed-loop system.

ES 2 332 292 T3

A second embodiment of blower assembly 70 is shown in FIGS. 39 and 40. The blower assembly of FIGS. 39 and 40 is similar to the blower assembly of FIGS. 38 and 39, except the following. In the blower assembly of FIGS. 39 and 40 the cyclone separator is not used. Instead, a vane separator 750 is located in the suction manifold housing section 84a on the suction side of the blower. The vane separator 750, which serves as a gas particle separation device, has a cylindrical configuration of vanes 752 separated by vertical grooves for the separation of heavy particles from the transport gas. A tangential flow of the transport gas out of the vane separator 750 removes the heavier particles, while the lighter particles and transport gas move into the vane separator 750 and then towards the impeller 708. The rod 724 Induction is located within the paddle separator 750 in the second embodiment of the blower assembly 70.

The powder transport system 32 in the present embodiment is configured as a closed loop system where excess particles and agglomerates are removed from the recirculation gas loop to prevent particles from clogging the discharge nozzles 532 of the dust aerator. . This is accomplished by the cyclone separator 702, the vane separator, or by any other device for separating gas particles.

The powder transport system 32 is configured with a secondary process gas loop between the gas particle separator and the discharge port 712 of the blower 700. This control loop can introduce secondary conditioning gas to regulate the environmental parameters of the primary recirculating transport gas, such as temperature, pressure, relative humidity, electrostatic levels, ion charge concentrations, gaseous element mixtures. , the seeding of small aerosol particles, etc.

The closed-loop powder supply system 32 is driven by the blower assembly 70, which is a hybrid of a pulsed blower coupled to the outer side of a cyclone separator or other gas particle separation device. The blower assembly 70 forms the main transport gas movement mechanism and includes a self-cleaning dust agglomerate filtration system. In addition, the transport gas is conditioned by the secondary process loop which controls the gas properties of the primary process loop. These two loops are nested together within the blow assembly 70. Blower assembly 70 includes an impeller 708 having a vane wheel configuration with volute curves between each impeller blade. The blade wheel impeller configuration produces dynamic shock waves in the form of pressure pulses that travel down tube 76 into aerator 72. These shock waves help break up, aerate, and disperse the compressed drug powder.

The blower features variable speed capability and is driven by blower motor 704. When the 704 engine operates beyond normal operating speeds, the transport gas acts as a recirculating gas scrubber that helps remove residual dust from the closed-loop conduit channels.

Fig. 41 shows a schematic block diagram of the gas conditioning system 730. The gas conditioning system 730 includes a secondary gas treatment loop that is different from the closed loop system for recirculation of transport gas and powder supply to die block 50. A portion of the recirculating transport gas is diverted to the secondary gas treatment loop near the discharge port 712 of the blower assembly 70. The conditioned gas is reintroduced into the circulating transport gas loop through induction rod 724. The gas conditioning system 730 includes a steam generator 800, coupled to a water supply 802 to rapidly generate water vapor, a desiccator 810 to reduce the relative humidity of the transport gas, valves 812 and 814 to select the generator 800 steam or desiccator 810, and filters 820 and 822.

The relative humidity of the transport gas can be measured by a detector, such as the detection chamber to be described later, positioned to detect the transport gas. When the relative humidity of the transport gas increases, valves 812 and 814 are connected to steam generator 800. The steam generator 800 includes a bubble generator and flash heaters to rapidly produce water vapor. Bypass gas in the secondary loop passes through filter 820, steam generator 800, and filter 822, thereby returning gas with higher relative humidity to induction rod 724. When the relative humidity of the transport gas decreases, valves 812 and 814 connect to desiccator 810. Transport gas diverted in the secondary loop passes through filter 820, desiccator 810, and filter 822, thereby returning gas with reduced relative humidity to induction rod 724.

Conditioning of the transport gas is accomplished by introducing a process treatment gas into the inner core of the cyclone vessel 720. The conditioned gas is introduced into the container at the end of the induction rod 724. Induction rod 724 is manufactured from a sintered metal or porous plastic polymer that allows the conditioned gas to mix uniformly with the recirculating transport gas without producing water droplets or heavy flow states. The process treatment gas loop is balanced by a rise and return leg on the discharge side of blower 700. A portion of the cyclone separator 720 or housing section 84a may be made of glass for visual inspection of the collected drug powder. If the collected dust can be recycled, it can be reintroduced into the hopper assembly 74, or it can be discarded.

Controlling the humidification of the powder during the operation of the powder conveying system is complicated by the fact that the exposed surface area of ​​the powder changes during the conveying process. Dust

ES 2 332 292 T3 is initially prepared in the agglomerated state. However, as the dust crumbles and disperses during gas transport, its exposed surface area increases significantly, in turn causing rapid moisture absorption. In order for a humidification process to be on the same level and to control this rapid dehydration of the transport gas loop, the gas treatment system must be capable of rapid forced hydration.

The 702 cyclone separator features an integral matched inlet manifold that penetrates the cyclone body with minimal hydraulic loss. The blower assembly features a large flow range and can serve as a system dust scrubber. The blower is equipped with a vane-wheel-like impeller that features curved, volute-shaped surfaces between each vane to efficiently transport fine powder aerosols and to prevent raking and re-agglomeration of the powder. The vane-wheel-like impeller directs the dynamic shock waves into the powder aerator 72 to aid in fluidization of the drug powder. Blower assembly 70 includes a gas conditioning system where a secondary gas treatment loop is introduced into the unit through induction rod 724 within the cyclone vessel. The gas conditioning system can control many gas parameters, such as relative humidity and temperature, static ion control, fine particle seeding, trace element seeding, gas catalyst activation, control gas / light sterilization, etc.

An embodiment of a detection chamber 850 for detecting the state of the transport gas in the powder transport system is shown in FIGS. 42 and 43. The transport gas, with the dust extracted to the extent practical, circulates through the detection chamber 850 in parallel with the dust transport system. The detection chamber 850 contains detectors for detecting transport gas parameters, such as relative humidity and temperature, to allow conditioning of the transport gas as described above.

The detection chamber 850 receives transport gas through an inlet tube 852 connected to the blower housing 710 of the blower assembly 70 and supplies transport gas through an outlet tube 854 connected to the suction manifold 84. Both the inlet tube 852 and the outlet tube 854 are insulated and can be configured as inner and outer tubes separated by spacer rings. The inlet tube 852 may be connected to the blower housing 710 perpendicular to the direction of the transport gas flow to limit the entry of the powder into the detection chamber 850.

As shown in fig. 43, the detection chamber 850 may include an upper housing 856 and a lower housing 858 having an interior volume that is approximately equivalent to the interior volume of die block 50. The detection chamber 850 may include a relative humidity detector 860, a temperature detector 862, and a pressure detector 864. In the embodiment of Figs. 42 and 43, the relative humidity detector 860 includes a temperature detector that allows for cross-checking with the temperature values ​​detected by the temperature detector 862. A discrepancy in the readings may indicate that the detectors are covered in dust and therefore do not provide accurate detection. An air deflector 866 is mounted in the lower housing 858. The detection chamber 850 provides an accurate detection of the transport gas states in the powder transmission system.

Figure 44 shows an illustrated representation of the powder filling and assembly process for an inhaler cartridge. A cartridge bottom 900 is inserted into the system in a cartridge tray and placed over a weight sensing probe 112a for filling. Cartridge bottom 900 is filled with medicament powder by powder dispensing module 54 as described in detail above. After filling, the top 902 of the cartridge snaps onto the bottom 900 of the cartridge to provide a complete cartridge 910 ready for sealed packaging.

As indicated above, the powder detection and dispensing apparatus of the present invention can be used to fill different types of containers. In another embodiment, the powder sensing and dispensing apparatus is used to fill a compact inhaler described in US Patent No. 6,923,175 issued August 2, 2005 to Poole et al. As illustrated in fig. 45, the bottom 920 of a compact inhaler cartridge is positioned over a weight sensing probe 112a for filling. The lower portion 920 of the cartridge is filled with medicament powder by the powder dispensing module 54 as described above. Then, the upper part 922 of the cartridge is coupled to the lower part 920 of the cartridge and a nozzle housing 924 is attached to the cartridge assembly. Finally, a dirt shielding cap 930 snaps onto mouthpiece housing 924 to provide a complete compact inhaler 932 ready for sealed packaging.

After various aspects of at least one embodiment of this invention have been described, it should be appreciated that various alterations, modifications, and improvements will readily occur to those skilled in the art. Such alterations, modifications, and improvements are part of this description and are within the scope of the invention. Accordingly, the above description and drawings are provided merely by way of example.