Powder dispensing and sensing apparatus and methods.

(54) Title: APPARATUS AND METHODS FOR SUPPLYING AND DETECTING DUST. (54) Title: POWDER DISPENSING AND SENSING APPARATUS AND METHODS.

(57) Summary

The present invention relates to a powder supply module (54) comprising: a housing (150) defining a powder inlet (130) for receiving powder, a powder outlet (158), and a conduit (152, 154) connecting the powder inlet (130) and the powder outlet (158); a feed rod (160) for moving powder through conduit (152,154) from powder inlet (130) to powder outlet (158); and a stem activator (162) to rotate the feed stem (169) in the conduit (152,154); the powder supply module is characterized in that the duct (152,154) includes a powder bed preparation area (156a) below the powder inlet (130), a powder bed compression area (156b) below the powder bed preparation area (156a) and a powder discharge area (156c) below the powder bed compression area (156b) and where the feed stem (160) comprises a shaft (170), a powder bed preparation element (164) in the powder bed preparation zone (156a) and a discharge element (166) within the dust discharge zone (156c).

(57) Abstract

Powder dispensing and sensing apparatus and methods are provided. The powder dispensing and sensing apparatus ineludes a tray support structure to receive a cartridge tray holding cartridges, a powder dispenser assembly including powder dispenser modules to dispense powder into respective cartridges of a batch of cartridges in the cartridge tray, a powder transport system to deliver powder to the powder dispenser modules, a sensor module including sensor cells to sense respective fill States, such as the weights, of each of the cartridges in the batch of cartridges, and a control system to control the powder dispenser modules in response to the respective sensed fill States of each of the cartridges of the batch of cartridges.

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Mexican Property

Industrial

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PATENT TITLE NO. 339072

Owner (s): MANNKIND CORPORATION

Address: 28903 North Avenue Paine, Valencia, California, 91355, USA

Name: APPARATUS AND METHODS TO SUPPLY AND DETECT POWDER. Classification: IC 8: B65B1 / 30

Inventor (s): TRENT A. POOLE; DAVID F. BONNEAU; PER B. FOG

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'Igency: Twenty

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of presentation of November 20, 2006 of the Patent Number: 311938

PRIORITY

Date: .-. And ¿j. · November 21, check of Venci lient patent of reference becomes tor jndamenl) conformity with the article 23 of ntada from the date of presi rechos.

lien subscribes to the present decree with fundamental Industrial Opportunity (Official Diaric di / 01/2004, 06/16/2005, 2 ^ 1/2006, laugh a), subsection iii) 4 ormed on 07/01/2002, 1 ®7 / 20O4,

I instituted

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Law of I; tion of the Lay gives the Property and 7 ° bis 2 of the

Number:

60 / 738,474 and this patent is valid for v * M9 years and will be subject to the payment of the fee to maintain

Federation (DOI ¡/ 05 / 2009,06 / 01/2010, 1st month I and III of the Regulation i 07/01/2004 and 07/09/2007); articles 1, 3, 4 », 1 r I ustrlal.

impro V¡ (gables, ntes los ¡y de la

1996, 12/26/1997, 17 15/1999, ¡/ 2012); Articles 1, 3 Industrial Property (DOF 1 iction V 2/1999, ion V Clause a), sub Clause Iii), 16 fraction i and III and || IIIβββΜΜ ·· Μ · ΜβΙΙβΙβΝΜΝ | 7/2004, delegates powers in the General Directors

04/08/2004 and 09/13/2007); 1st, 3rd and 5th (ncisoa) and the penultimate paragraph of the Agreement that i Deputies, Coordinator, Divisional Directors, Holders of the Regional Offices, Divisional Subdirectors, Departmental Coordinators and other subordinates of the Mexican Institute of Industrial Property. (DOF 12/15/1999, amended on 02/04/2000, 07/29/2004, 04/08/2004 and 09/13/2007).

Issue Date: May 9, 2016

DEPUTY DIVISIONAL DIRECTOR OF EXAMINATION OF PATENT FUND, MECHANICAL, ELECTRICAL AREA AND REGISTRY OF INDUSTRIAL DESIGNS AND

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PEDRO

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Arenal No. 550. Floor 1,

Col. Pueblo Santa María lepaban,

Xochimilco. CP 16020,

Mexico City

Tet. (55) 53 34 07 Oü www iropi

MX / 2016/36528

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CROSS REFERENCE TO RELATED APPLICATION

This request claims priority based on the Request for

Provisional Patent Serial No. 60 / 738,474, filed on November 21, 2005, which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to methods and apparatus for supplying and detecting powder, and more particularly, to methods and apparatus for supplying precisely controlled amounts of powder to multiple cartridges and for individually detecting the fill status of the cartridges. The powder may contain a drug and the cartridges can be used in an inhaler. However, the present invention is not limited to this application.

BACKGROUND OF THE INVENTION

IMPI

MEXICAN INSTITUTE Dt THE INDUSTRIAL PROPERTY

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It has been proposed to deliver types of drugs to patients by inhaling a powder as a delivery mechanism.

A particular example uses diketopiperazine microparticles known as Technosphere® microparticles. Technosphere microparticles 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 on April 2, 1996 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 on September 3, 2002 to Steiner et al; and US Patent No. 6,652,885, issued on November 25, 2003 to Steiner et al. One use of these microparticles is insulin delivery by inhalation. An inhaler that has a replaceable cartridge or capsule that contains a powdered drug is used for drug delivery.

Administration of drugs by inhalation normally requires a very small amount of powder in the inhaler cartridge. As an example, applying insulin using Technosphere microparticles may require a dosage as small as 10 milligrams of the powder. Additionally, the drug dose must be highly accurate. A lower than specified dose may not have the

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desired therapeutic effect, while a higher dose than ^ peemcada ^^^ ^{Π J} DEÍAPROPIEDAO V'tas.xA⁵¹

INDUSTRIAL ^ *** ~ 2 ^ _ may have an adverse effect on the patient. Additionally, although Technosphere microparticles are highly effective for inhalation drug delivery, their platelet surface structure causes Technosphere powders to be cohesive and somewhat difficult to handle.

In the marketing of inhalation drug delivery, large numbers of cartridges containing the drug must be produced in an efficient and cost-effective manner. An accurate dose of the powder must be delivered to each cartridge and the drug dose in each cartridge must be verified. Manufacturing techniques and equipment must be capable of high total performance to meet demand and must be capable of handling powders, which are cohesive and therefore do not flow freely. Existing manufacturing techniques and equipment have not been adequate to meet these demands.

Accordingly, there is a need for novel methods and apparatus for dust delivery and detection.

BRIEF DESCRIPTION OF THE INVENTION

Systems and methods are provided for simultaneously delivering precisely controlled doses of a powder in multiple cartridges. The powder may contain a drug and the cartridges can be used in inhalers. The fill status of each cartridge, &lt;

INSTITUTE '1 C- *' ^;

DELA = i \ the weight of the powder, is detected during filling, and the powder supply modules are individually controlled in response to weighing to ensure accurate dosing. The system operates at high speed and can be very compact to allow the production of filling operations with minimal free surface requirements.

In accordance with a first aspect of the present invention, a powder supply and detection apparatus comprises a tray support structure for receiving a cartridge tray that supports cartridges, a powder supply assembly including powder supply modules for supply the powder into the respective cartridges of a batch of cartridges in the cartridge tray, a powder transport system to deliver the powder to the powder supply modules, a detection module including detection cells for detecting the respective fill states of each of the cartridges in the cartridge batch, and a control system for controlling the powder supply modules in response to the respective detected fill states of each of the cartridges in the cartridge lot.

Powder supply modules, powder transport system and detection cells can be configured to supply powder simultaneously to the batch of cartridges and simultaneously detect the fill status of each cartridge in the batch of cartridges.

The detection cells can comprise the weighing of the detection cells. The cartridge tray can be configured for cartridges in a two-dimensional group of rows and columns.

MEXICAN INSTITUTE OF INDUSTRIAL FROFIEDAD

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The powder transport system may include a blower assembly to move a transport gas, a powder aerator to deliver powder to the powder distributor assembly, and a hopper assembly to supply the powder to the powder aerator. The powder transport system may additionally include a manifold that couples the transport gas from the dust distributor assembly to the blower assembly to form a recirculating closed circuit gas transport system. The powder transport system may include a gas conditioning system to control the relative humidity, temperature, or both, of the transport gas.

Each of the powder supply modules can include a housing that defines a powder inlet to receive a powder from the powder transport system, a powder outlet, and a powder delivery duct connecting the powder inlet and outlet and a feed mechanism to move the powder through the duct from the powder inlet to the powder outlet.

The feed mechanism may include a stem to move the powder through the conduit, an activator to operate the feed stem, a valve to control the outlet, and an activator to operate the valve. The feed stem can include a shaft and a helical opening gap frame that includes a separate shaft fixed to the shaft. The separate mast may have a helical arrangement on the shaft. The

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power stem may additionally comprise of one or more cables secured between some or all masts

...

OF THE FRCW.DAD k INDUSTRIAL separated. Cables can include one or more helix arrangements secured between the ends of the masts and one or more chevron arrangements secured between the masts at selected radial locations. In some embodiments, each cable is secured so that it can slide through the holes in the intermediate masts and is attached at each end to one of the masts.

The feed stem additionally includes a discharge element fixed to the shaft below the helical open space frame. In different embodiments, the discharge element can be implemented as a modified stem having a double helix configuration, a roll pin, and a support element used in combination with an orifice element or worm gear blades used in combination with a hole element.

The powder dispenser assembly may include an arrangement block that has an arrangement of vertical ports. Powder supply modules can be mounted on the respective vertical ports of the disposal block. The layout block may include channels for delivering powder to the powder supply modules. The powder supply modules can be provided with powder inlets aligned with the channels in the disposition block such that the powder is delivered to a row of the powder supply modules through a channel in the disposition block . Each channel

INSTITUTO MEXICANO disposal can pass through the disposal block to make ^ ocircula ^ · ® again the transport gas to the blower assembly, your pipes erreí disposal block may have sufficient capacity to store dust for one or more supply cycles dust from the powder supply modules.

The hopper assembly may include a hopper body defining a powder tank and a granulating device at the bottom portion of the powder tank. The granulation device may comprise first and second agglomerate rollers and first and second motors to drive the first and second agglomerate rollers, respectively. Each of the agglomerate rollers can be provided with a plurality of pins or a plurality of separate discs.

The blower assembly may include a blower to move a transport gas through a recirculating transport gas system, and a gas-particle separation device to remove dust agglomerates from the recirculating transport gas. In some embodiments, the gas-particle separation device is implemented as a cyclone separator, and in other embodiments, the particle separation device is implemented as a propeller separator. The blower may include an impeller to move the transport gas, an impeller motor to rotate the impeller, and a blower housing that encloses the impeller and has a discharge port to supply the transport gas to the powder aerator. The assembly of »MEXICAN INSTITUTE

G £ LA r / riíDAD Q -.,. - ·, λ ^ further comprising an induction rod for introducing a conditioned transport gas into the transport gas flow.

The powder aerator can include a collector block that defines a powder inlet, powder outlet ports coupled to the powder distributor assembly, and a gas inlet coupled to the blower assembly. The powder aerator may additionally include a pneumatic broom to deliver powder through risers to the powder outlet ports and a dump valve to supply a quantity of powder from the powder inlet to the pneumatic broom. The discharge valve also seals the closed loop transport gas system from the external environment. The dust aerator may additionally include a bypass manifold coupled to the powder outlet ports and a crossover valve that directs selected portions of the transport gas from the gas inlet to the air broom and to the bypass manifold.

In accordance with a second aspect of the present invention, there is provided a method of supplying and detecting the powder. The method comprises placing cartridges in a cartridge tray, simultaneously supplying powder in a batch of cartridges in the cartridge tray, and simultaneously detecting the fill status of each of the cartridges in the batch of cartridges.

In accordance with a third aspect of the present invention, a powder aerator comprises a manifold block defining a powder inlet, powder outlet ports, and a powder gas inlet.

FROM THE PHOPIEOAD V *,_Iecfj INOUSTRÍAL pneumatic broom to deliver powder to the powder outlet ports; a discharge valve to supply a quantity of powder from the powder inlet to the air broom; a diversion manifold coupled to the powder outlet ports; a crossover valve to direct selected portions of the transport gas from the gas inlet to the air broom and to the diverter manifold.

In accordance with a fourth aspect of the present invention, a powder dispenser assembly comprises an arrangement block that

It includes an arrangement of vertical ports and horizontal channels that intersect each of the vertical ports; and powder supply modules mounted in the respective vertical ports to the layout block, each of the powder supply modules has powder inlets that communicate with the channels in the layout block is a distributor for each of the modules powder supply.

In accordance with a fifth aspect of the present invention, a powder transport system comprises a powder dispenser assembly for supplying powder within the cartridges; a blower assembly to move a transport gas; and a powder aerator to deliver the powder entering the transport gas to the powder distributor assembly.

In accordance with a sixth aspect of the present invention, a powder supply module comprises a housing defining a powder inlet for receiving the powder, a powder outlet and a powder delivery duct connecting the powder inlet and the output Fe

INDUSTRIAL feed stem to move powder through delivery chute

MWM »ΛΙΜΓΛ, -Λ of dust; an activator to operate the feed stem; a valve to control the powder output; and an activator to operate the valve.

In accordance with a seventh aspect of the present invention, a blower assembly comprises an impeller for moving a transport gas; an impeller motor to rotate the impeller; a blower housing enclosing the impeller and having a discharge port for the transport gas; a collector to receive the transport gas; and a gas-particle separation device fixed to the collector to accumulate the agglomerates that enter the transport gas.

In accordance with an eighth aspect of the present invention, a powder handling apparatus comprises a tray support structure for receiving a cartridge tray supporting at least a first batch of cartridges and a second batch of cartridges; a supply sub-system for supplying the powder within a batch of the cartridges in the cartridge tray; and a tray placement mechanism for sequentially moving the cartridge tray into position of the first and subsequent batches of cartridges in the cartridge tray in alignment with the supply subsystem.

In accordance with a ninth aspect of the present invention, a method of supplying powder into a cartridge comprises placing a cartridge under a supply module having a powder containing hopper, opening a valve controlling the hopper, which operates a stem d

INSTITUTE OF ΙΛ

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in the hopper to supply the powder through the valve to the cartridge, and close the valve when the desired fill state of the cartridge has been reached.

The operation of the feed stem may include rotating the feed stem and reversing the rotation of the feed stem to the condition of the powder in the hopper. The feed stem can be rotated at variable speeds and can be agitated during rotation. The feed stem can reciprocate, causing the stem to rotate rapidly clockwise and counterclockwise during some portion of one or more revolutions. The method may include detecting a weight of the powder in the cartridge and closing the valve when the detected weight is equal to or greater than a target weight. Opening the valve may include rotating a valve element in a selected direction, and closing the valve may include rotating the valve element in the same direction. Opening the valve may include subsequently positioning the valve element with respect to the dispensing nozzle opening.

The feed stem can be rotated at a selected maximum speed during a first portion of the fill cycle and subsequently rotated at a reduced speed during a second portion of the fill cycle. The second portion of the fill cycle can start when the powder distributed inside the cartridge is equal to or greater

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The proportional control and / or the control t 't? · That a selected weight.

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can be used during any portion of the fill cycle.

In accordance with a tenth aspect of the present invention, the dust detection and supply apparatus is a highly compact modular system which can be operated in both a research laboratory and a production plant. This feature facilitates regulatory approval for a common machine and results in reduced costs due to common technical support and training and reduced inventory parts.

In accordance with an eleventh aspect of the present invention, the powder delivery and detection apparatus has the ability to fill inhaler cartridges, once compact inhalers and multipurpose inhalers are used. This capability can be achieved by relatively minor changes to the system that delivers the containers to be filled to the apparatus to supply and detect dust.

BRIEF DESCRIPTION OF THE DRAWINGS

MEXICAN INSTITUTE CE LA

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

Figure 1 is a perspective view of a powder supply and detection apparatus in accordance with an embodiment of the present invention;

Figure 2 is an exploded view of the dust detector and supply apparatus of Figure 1;

Figure 3 is a partial vertical cross-sectional view of the powder supply and detection apparatus;

Figure 3A is a schematic block diagram of the powder supply and detection apparatus;

Figure 4 is a perspective view of the powder supply modules, cartridges, a cartridge tray, and the weight sensing cells;

Figure 5 is a perspective view of a powder transport system;

Figure 6 is a cross sectional diagram of an arrangement block and a powder transport system;

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

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Figure 8 is a perspective view of your arrangement;

MEXICAN INSTITUTE OF LA PRÜFltO.AD

INDUSTRIAL

Figure 9 is an exploded view of an arrangement block of Figure 8;

Figure 10 is a perspective view of a powder supply module;

Figure 11 is an exploded view of the powder supply module of Figure 10;

Figure 12 is a schematic cross sectional diagram of a Lower end of the powder supply module;

Figures 13A-13B illustrate a feed stem in accordance with an embodiment of the present invention;

Figures 14A-14F illustrate a feed stem in accordance with another embodiment of the present invention;

Figures 15A-15D illustrate a feed stem according to a further embodiment of the present invention;

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

Figure 17 is a block diagram of a control circuit for a single powder supply module and a cell for weight detection;

powder supply;

Figure 18 is a flow diagram of a

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Figure 19 is a flow chart of a cartridge cycle;

detection;

Figure 20;

Figure 20 is a perspective view of the

Figure 21 is an exploded view of the detection module of

Figure 22 is a perspective view of a first embodiment of a weight detection probe;

Figure 23 is a perspective view. of a second embodiment of a weight detection probe;

Figure 24 is a perspective view of a first embodiment of a powder aerator;

Figure 25 is an exploded view of the dust aerator of the

Figure 24;

Figure 26 is a perspective view of a pneumatic broom used in the dust aerator of Figure 24;

Figure 27 is an exploded view of the pneumatic broom of Figure 26;

Figures 28A-28C are cross-sectional views of the powder aerator of Figure 24;

Figure 29 is a perspective view of a second embodiment of a powder aerator;

Figure 29;

Figure 30 is an exploded view of the aerator d

INSTITUTE ΜΞΌνΑΝΟ É¹OF THE PROPERTY

INDUSTRIAL

Figure 31 is a perspective view of a pneumatic broom used in the dust aerator of Figure 29;

Figure 32 is an exploded view of the pneumatic broom of Figure 31;

Figure 33 is a perspective view of a first embodiment of a hopper assembly;

Figure 34 is an exploded view of the hopper assembly of the

Figure 33;

Figure 35 is a perspective view of a second embodiment of a hopper assembly;

Figure 36 is an exploded view of the ia hopper assembly

Figure 35;

Figure 37 is a perspective view of a first embodiment of a blower assembly;

Figure 38 is an exploded view of the blower assembly of Figure 37;

Figure 39 is a perspective view of a second embodiment of a blower assembly;

Figure 40 is an exploded view of the blower assembly of Figure 39;

Figure 41 is a schematic diagram of uijs ^ jnj ^ íje

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Figure 42 is a perspective view of jjxusisiema.de ...........

powder delivery incorporating a detection chamber;

Figure 43 is an exploded view of the detection chamber shown in Figure 42;

Figure 44 is a pictorial representation of a filling procedure for an Inhaler cartridge; and

Figure 45 is a pictorial representation of a filling procedure for a compact inhaler.

DETAILED DESCRIPTION OF THE INVENTION

The powder supply and detection apparatus 10 according to an embodiment of the present invention is shown in Figures 1 to 7. One purpose of the apparatus is to supply powder in multiple cartridges 20 and to detect and control a fill status of each of the cartridges such that each of the cartridges receives a precisely controlled amount of the powder. As used herein, the term "cartridge" refers to any container or capsule that has the ability to hold a powder, usually a powder that contains a substance of a drug. As used herein, the term "fill" includes fill and partially fill, because each cartridge is not normally filled

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INSTITUTO MEX fcE LA Γ '»ΟΓΙΓ.

the parade is up to the capacity and in fact it can be filled only small with its capacity. As described below, you can use it to fill an Inhaler cartridge or a compacted inhaler, although it is not necessarily limited to the type of container to be filled.

The cartridges 20 can be held in a cartridge tray 22 that is placed in a tray support frame 24 for processing. The cartridges can be held in a row and column arrangement. In one example, cartridge tray 22 holds forty-eight cartridges 20 in a 6 x 8 arrangement. The configuration of the cartridge tray 22 and the corresponding configuration of the apparatus 10 are determined by way of example only and are not limiting of the scope of the present invention. It should be understood that the cartridge tray 22 may be configured to hold a different number of cartridges and that the cartridge tray 22 may have a different tray configuration within the scope of the present invention. In another embodiment described below, the cartridge tray can hold 192 cartridges. Cartridge tray 22 can be placed on support frame 24 and removed from support frame 24 by a robot.

The components of the dust detection and supply apparatus

10, in addition to the tray support frame 24, include a powder dispenser assembly 30 to supply the powder in the cartridges 20, a powder transport system 32 to deliver the powder to the lAAtkiü assembly.

powder dispenser 30 and a detection module 34 for detecji ^ tl ^ fajbd ''

MEXICAN INSTITUTE

V IJU LA IWHi-W · »&gt; ► * s for filling each of the cartridges 20. The apparatus for sumihlstroy detection of dust 10 additionally includes a frame 40 for TnóntáTel tray support frame 24, the dust distributor assembly 30 , the powder transport system 32 and the detection module 34, and the activators 42 for moving the powder distributor assembly 30 and the powder transport system 32 with respect to the cartridges 20.

The powder dispenser assembly 30 includes an arrangement block 50 having a vertical port arrangement 52 and a powder supply module 54 mounted to each of the vertical ports of the arrangement block 50. The arrangement block 50 may be configured to pair the cartridge array 20 in the cartridge tray 22 or a subset of cartridges in the cartridge tray. In the above example of a cartridge tray holding forty-eight cartridges, layout block 50 may have a 6 x 8 vertical port layout 52 and provide mounting for forty-eight powder supply modules 54. In this embodiment, powder supply modules 54 are mounted on one-inch centers. It will be understood that a different separation arrangement can be used within the scope of the present invention. As shown in Figure 8, disposal block 50 additionally includes powder storage and transport channels 60a, 60b, 60c, 60d, 60e, 60f, 60g and 60h, with one channel for each phyta of six supply modules. powder 54 in this mode. The powder is delivered by the powder transport system 32 to the modules of the 'INSTITUTO MEXICANO DELA ESDI IEDAD powder 54 through each channel in the disposal block 50, described below. Each channel preferably has enough 'TfT'voíumefi' to store powder for various powder supply cycles.

In the embodiment of Figures 1 to 7, the powder transport system 32 includes a first powder transport system 32a for delivering powder to a first group of four channels 60a, 60b, 60c and 60d, in an arrangement block 50 and a second powder transport system 32b to deliver powder to a second group of four channels 60e, 60f, 60g and 60h in disposal block 50. Each of the powder transport systems 32a and 32b includes a blower assembly 70 to move a transport gas through the powder transport system, a powder aerator 72 to deliver powder to the powder distributor assembly 30, and a Hopper assembly 74 to supply powder to a powder aerator 72. In other embodiments, a single powder transport system or more than two powder transport systems can be used.

The blower assembly 70 is coupled through a tube to a gas inlet 78 of the powder aerator 72 and produces a flow of transport gas through a gas inlet 78. The powder aerator 72 includes a powder inlet 80 to receive the powder from the hopper assembly 74. The powder is delivered by the powder aerator 72 through four powder outlet ports 82 to the input ends of the respective channels in the disposal block 50. Dust is transported through

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from the respective channels to the powder supply modules row of the powder dispenser assembly 30. The powder is uisu iuuiuo individually to the cartridges 20 by means of the supply modules ¿feT 'powder 54 as described below.

Channels 60a-60h, pass through the layout block

50, and a matched suction manifold 84, is coupled to the outlet ends of the channels. The suction collector 84 of the first powder transport system 32a is connected to the outlet ends of the channels 60a-60d, and the suction manifold 84 of the second powder transport system 32b is connected to the outlet ends of the channels 60a-60h. The suction manifold 84 returns the transport gas to the blower assembly 70, thereby forming a closed loop recirculating gas transport system. In other embodiments, the powder transport system may use an open circuit gas transport system. Any powder not delivered to the powder supply modules 54 or stored in the channels returns through the suction collector 84 to the blower assembly 70. As discussed below, blower assembly 70, in some embodiments, may include a gasparticle separation device to retain large powder agglomerates, while small powder agglomerates are recirculated to powder aerator 72 to be delivered to the powder dispenser system 30. As discussed further below, each powder conveyor system can

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include a gas conditioning unit to control the relative I and / or temperature of the recirculating transport gas.

The powder transport system 32 can include testers to determine the level of dust in the different components of the powder transport system. Hopper assembly 74 may include a hopper level detector for detecting the level of dust in the hopper assembly container 74. Dust aerator 72 may include a discharge valve level detector for determining the level of dust in the dust aerator discharge valve 72. Blower assembly 70 may include a large chip level detector. A distributor 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 the level of dust, for example. The dust level detectors can be used to control the operation of the powder delivery system 32 and load the powder supply modules 54 with the powder.

Detection module 34 (Figure 20) can include a detector housing 100 (Figure 21) and an arrangement of detector assemblies 110 mounted on detector housing 100. In the illustrated embodiment, each of detector assemblies 110 includes two cells Detection 114 (Figure 3) and associated circuit systems. Therefore, a detection assembly 110 is used with two powder supply modules 54. In other embodiments, each detector assembly can include a single detection cell or more than two detection cells. The number of detection assemblies 110 and the array of deteft assemblies

INSTITUTE V.EXJCANO the arrangement may be such that the detection cells 114 coinctdeBocwH the configuration of the cartridges 20 in the cartridge tray-22 ^ t «$ 'St» b »- group of cartridges in the cartridge tray. For example, of a cartridge tray 22 holding forty-eight cartridges 20 in a 6 x 8 arrangement at one-inch centers, detection module 34 may include twenty-four detection assemblies 110, which provide forty-eight detection cells 114 in a 6 x 8 arrangement on one-inch centers. In the embodiment of Figures 1 to 7, each of the detection cells 114 is a weight detector for detecting the weight of the powder delivered to the respective cartridge 20. A weight detection probe 112 is attached to each of the cells detection 114 and contacts the lower end of the cartridge 20 through an opening in the cartridge tray 22.

Detection cells 114 individually detect the fill status of each of the cartridges 20 during powder delivery, such that the powder supply can be terminated when the desired amount of powder has been dispensed into each of the cartridges 20. Detection cells 114 are preferably weight detectors, which monitor the weight of cartridge 20 during the powder delivery procedure and are accurate to 5 to 10 micrograms in the present embodiment. An electrobalance beam is typically used as a weight detector in high precision, high speed, and repeatability applications with very small weights.

The physical configuration of the detection assembly • S. i.¹,

INSTITUTO MEXICANO is a consideration in systems where the dust supply modules 54 are closely separated, such as in ether ceters ^{to go}inch. Preferably, the weight sensing assemblies 110 can be placed in an arrangement that matches the configuration of the cartridge tray 22 and the powder supply modules 54. In a preferred embodiment, the sensing assemblies 110 have a vertical configuration and two detection cells 114 are packed together to form a detection assembly. Mechanical weight sensing components are located at the top of the assembly, the electrical circuitry is located below the mechanical components, and an electrical connector is connected at the bottom. Detection assemblies can be mounted in an arrangement to detect weight in one-inch centers.

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

The powder delivery and detection apparatus 10 has been described as having powder delivery modules 54 and detection cells 114 mounted on one-inch centers. It will be understood that a greater or lesser separation between components can be used! | ^ NJBb jd ^

MEXICAN INSTITUTE Ί scope of the present invention. Additionally, the fixtures 10 are not necessarily mounted in a uniform arrangement. For example, the x-direction spacing between components may be different from the y-direction spacing between components, or a row of an arrangement may be offset from an adjacent row.

During operation, the cartridge tray 22 supporting the cartridges 20 is placed in the tray support frame 24, preferably by a robot or other automation mechanism. Cartridge tray 22 is lowered so that cartridges 20 are lifted from cartridge tray 22 by weight sensing probes 112 onto respective sensing assemblies 110 and supported by probes 112. Cartridge tray 22 can be provided with openings at each cartridge location to allow probes 112 15 to pass through cartridge tray 22 and lift cartridges 20. Accordingly, each cartridge 20 can be weighed by one of the Detection cells 114 without interference from the cartridge tray 22. In some embodiments (Figures 22 and 23), probe 112 includes a three-point holder for cartridge 20. In other embodiments, probe 112 includes a cylindrical holder 20 for cartridge 20. Powder dispenser assembly 30 is lowered into a supply position. In the supply position, each of the powder supply modules 54 is positioned slightly above and in alignment with one of the cartridges 20.

<img file="MX339072B_D0023.tif" />

As shown in Figure 2, frame 40

OF THE PROPERTY \ ! INDUSTRIAL lower frame 40a, middle frame 40b and upper frame 40c. The lower frame 40a and the middle frame 40b are secured to a base plate 41. The upper frame 40c provides mounting for a tray support frame 24, the powder dispenser assembly 30 and the powder transport system 32. The block Array 50 connects to actuators 42 and moves up or down when activators 42 are energized. Detection module 34 is mounted in a fixed position within Lower frame 40a and middle frame 40b.

As discussed below, the powder transport system 32 can operate continuously or at intervals. Powder supply modules 54 are activated to supply powder to cartridges 20. Powder supply to cartridges 20 is performed simultaneously, such that all cartridges in the cartridge tray

22 or a subset of the cartridges in a cartridge tray receives the powder simultaneously. As the powder supply progresses, the cartridge weights 20 are detected by the respective detection cells 114. The output of each detection cell 114 is coupled to a controller. As discussed below, each controller compares the detected weight with a target weight which corresponds to the desired amount of powder. As long as the detected weight is less than the target weight, the powder supply continues. When the detected weight is equal to or greater than the target weight, the controller commands the corresponding supply module 54 to complete the IqM supply operation. ® íi

<img file="MX339072B_D0024.tif" />

filled, can the corresponding cartridge be marked as dérécfüóso? '' 'Accordingly, the supply and detection of weight vo and the detection of weight continue simultaneously for a batch of cartridges in cartridge tray 22. The batch may include all cartridges in cartridge tray 22 or a cartridge subgroup in the cartridge tray. A powder supply cycle can include simultaneous powder supply and weight detection of a batch of cartridges and achieves 100% inspection and control of powder supply.

In one embodiment, the number and spacing of cartridges in cartridge tray 22 matches the number and spacing of powder supply modules 54 in apparatus 10. In other embodiments, the cartridge tray may have a number of cartridges. and a different separation between cartridges that is different from the configuration of the powder supply modules 54. For example, the cartridge tray may be configured to hold a multiple of the number of powder supply modules 54 and have a smaller gap between the cartridges than the gap between the powder supply modules 54. By way of example only, The cartridge tray can be configured to hold 192 cartridges 20 spaced about half an inch center. With this arrangement, a 12 x 16 half-inch cartridges arrangement occupies the same area as a 6 x 8 cajuj ^ sjpfej arrangement: INSTITUTO MEXICANO ·. - FROM THE OWN ΠΑΠ L '* one-inch centers.^!’^ÍUKT'^iíL

As shown in Figure 7, the “cartUí5bó'22” tray can be moved in a horizontal direction using a tray positioning mechanism 120 to align batches of different cartridges with the powder supply modules 54. Cartridge 22 is placed in a tray support frame 24 for processing. The tray positioning mechanism 120 includes an X-direction activator 230 coupled to the tray support frame 24 and a Y-direction activator 232 coupled to the tray support frame 24. Accordingly, the tray support frame 24 and the Cartridge tray 22 can be moved in a horizontal XY plane for the positioning of batches of cartridges relative to powder supply modules 54 and detection cells 114.

The support 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 arrangement of 48 powder supply modules 54. Powder is supplied in the first batch of cartridges and the cartridge tray is then moved to a second XY position (0.0.5) to align a second batch of 48 cartridges with the arrangement of the powder supply modules 54. The tray cartridge is then moved to a fourth XY position (0.5,0.5) to align a fourth batch of 48 cartridges with the arrangement of the 48 modules of sjmjfe ^ rjpdj \ INSTITUTO McZíCAÍ'O

DE ΕΛ) ^Fí (powder 54. The powder is supplied in a fourth batch of cartridges to complete the processing of the 192 cartridges. In the example '^ rtrerfür;' W '' '' '' '' 'order of tray positions and Cartridge batch order can be changed.

It should be understood that this procedure can be applied to different tray arrangements with a different spacing between cartridges, different numbers of cartridges, and the like. In these embodiments, the cartridge tray is displaced in the horizontal plane to achieve alignment between the cartridge batches and the arrangement of the powder supply modules. The cartridge lot usually matches the arrangement of the powder supply modules 54. However, in some applications the batch may have fewer cartridges than the number of powder supply modules.

Arrangement block 40 is shown in Figures 8 and 9.

As previously described, disposal block 50 is provided with powder storage and transport channels 60a, 60b, 60c, 60c, 60d,

60e, 60f, 60g and 60h, one channel corresponds to each row in the arrangement of the powder supply modules 54. Each of the channels 60a-60h extends through the arrangement block 50 and intersects the vertical ports 52 in the corresponding row of the layout. In the embodiment of Figures 1 to 7, the powder transport system 32a delivers the powder to one side of the disposal block 50, and the powder transport system 32b

<img file="MX339072B_D0025.tif" />

delivers the powder to the opposite side of the consequent disposal block, Figures 8 and 9 show the ends of the channels 60a-60d and the outlet ends of the channels 60e-6OFT

In the embodiment of Figures 8 and 9, channels 60a-60h have sections grooved cross and are parallel. As shown in Figure 10, each of the powder supply modules 54 is provided with a powder inlet 130 in the form of a slot-shaped opening that passes through the powder supply module. When the powder supply modules 54 are mounted in an arrangement block 50, the powder inlets 130 are aligned with the corresponding channel in the arrangement block 50. The powder inlets 130 and the channels 60a-60h, preferably have sections cross sections of equal size and shape and polished to provide smooth interior surfaces. Each channel in layout block 50 and corresponding powder inlets 130 in powder supply modules 54 define a passage through layout block 50 for delivery of powder to each of powder supply modules 54. Powder is supplied to each of the powder supply modules 54 through powder inlet 130. The powder inlet 130 is configured as a through opening, such that part of the powder transported through the channel is delivered to the first powder supply module 54 and another part of the powder is transported through the powder inlet 130 and the channel in layout block 50 to successive powder supply modules 54.

<img file="MX339072B_D0026.tif" />

Additionally, channels 60a-60h serve a

INSTITUTO MEXICANO DELAPSOH'DAO dust storage. Channels 60a-60h can store more'jÜdiVü than is necessary to supply a single batch of cartridges. In one embodiment, the powder transport system 32 operates at intervals. Sufficient powder for a number of batches of cartridges 20 is supplied from hopper assembly 74 to channels 60a-60h. Then, the powder is supplied to several batches of cartridges 20 until the powder supply in the supply modules 54 becomes low. In other embodiments, the powder is continuously supplied to channels 60a-60h, and channels 60a-60h serve as temporary storage for storing powder not supplied to cartridges 20.

The closed circuit pneumatic powder transport system 32 feeds the agglomerate particles into the disposal block 50 from the powder aerator 72. The transport gas is then circulated back to the powder aerator 72. The gas from the Transport can be conditioned by a secondary procedure control gas that is supplied to blower assembly 70.

Disposal block 50 functions as a dynamic powder storage device that feeds batch faces or continuous loads of drug powder to individual powder supply modules 54. More generally, disposition block 50 includes one or more channels used to transport powdered aerosols and / or powdered drug agglomerate pastes to an array of

<img file="MX339072B_D0027.tif" />

INSTIT - D

Dt * ·

INSTIT

OF powder supply. Arrangement block 50 can operate on open circuit or closed circuit gas transportation. Powder aerator 72 and disposal block 50 transform into liquid, entering and transporting the drug powder into channels of disposal block 50.

Arrangement block 50 can provide the main structural support for associated components and subsystems, such as the dust aerator 72, the hopper assembly 74, the suction collector 84, and the pump assembly 70. Additionally, the Arrangement block 50 maintains an arrangement of powder supply modules 54 for supplying powder to an array of cartridges. In a preferred embodiment, the layout block includes a main block 132, a top plate 134, and a bottom plate 136. The plates 134 and 136 include O-rings which serve as guides and seals for the powder supply modules 54. This layout block further includes bearings 140 and clamping handles 142 for attaching the layout block to the frame elements.

During operation, the powder is transported through each of the channels 60a-60h by the transport gas and is delivered to each of the powder supply modules 54 in a controlled particle deposition procedure. Dust falls under the action of gravity in each of the dust supply modules 54. Any dust that passes through the channel without falling into one of the dust supply modules and without being stored returns through the dust collector.

<img file="MX339072B_D0028.tif" />

<img file="MX339072B_D0029.tif" />

pump assembly 70.

Each of the powder supply modules 54 supplies powder within a cartridge 20. The powder dosage is typically within the range of 5 to 30 milligrams, although the dose is not limited to this range.

As shown in detail in Figures 10 to 16B, the powder supply module 54 includes a powder supply housing 150 having a lower housing section 150a, a middle housing section 150b, an upper housing section 150c and a cover 150d. Powder supply housing 150 may have an elongated configuration with a small cross section to allow close separation in disposal block 50. As noted above, the powder supply modules 54 can be mounted on one-inch centers. The middle housing section 150b includes a powder inlet 130 and a cylindrical conduit 152 extending downward from the powder inlet 130 to the lower housing section 150a. The lower housing section 150a includes a tapered conduit 154 extending downward to a supply nozzle 158, which is sized to be compatible with the cartridge 20. The tapered conduit 154, which may be conical in shape, provides a transition from the dimension of the cylindrical duct 152 to the dimension of the supply nozzle 158. Together, the cylindrical conduit 152 and the tapered conduit 154 define a supply hopper 156 to hold the powder to be supplied. ¿

OF THE ΡΠΟΠΕΓΑΙ) INDUSTPJ / d.

supply hopper 156 is referred to as a volume powder bed. Supply nozzle 158 is configured to supply powder into cartridge 20.

Powder supply module 54 further includes a feed stem 160 to move powder down in a controlled manner through supply hopper 156 to nozzle 158, a stem activator 162 to activate stem 160, a supply fill valve 180 at the bottom end of hopper 156, and valve actuator 182 for opening and closing valve 180. The stem actuator 162 can be coupled to the feed stem 160 by a flexible coupling 186 or other coupling which can provide agitation, displacement or both of the vertical stem, in addition to rotation. The powder supply module 54 further includes a circuit card 184 having a circuit system for controlling the stem actuator 162 and a valve actuator 182 and for communicating with the control circuit system that controls the operation of the powder supply 54.

Fill valve 180 may include valve element 190 implemented as a gear provided with an eccentrically located valve opening 191. Valve element 190 can be mounted in a lower housing section 150a for rotation about an axis, such that valve opening 191 can be rotated in alignment with supply nozzle 158, as shown in Figure

16Α, and can be spun out of alignment with the JteLWmini!

^: INSTITUTO fv - o,

OELAPR'.PT Ό

158 as shown in Figure 16B. When the valve opens Wyla supply nozzle 158 are aligned or partially aligned, fill valve 180 opens and powder is delivered into a cartridge.

When valve opening 191 is not aligned with supply nozzle 158, fill valve 180 closes and powder is not supplied. Preferably, fill valve 180 is a type that can be partially opened, as described below.

Valve element 190 of fill valve 180 may be coupled to valve actuator 182 by a conductive assembly which includes a lower gear 192 that meshes with valve element 190 gear, a drive shaft 193 extending from a lower portion of supply module 54 to an upper portion thereof where valve actuator 182 is mounted, an upper gear 194 attached to the upper end of drive shaft 193 and an upper gear 195 attached to valve actuator 182. Upper gears 194, 195 are intermeshed such that valve element 190 is rotated when valve actuator 182 is energized.

The gear 195 can match the valve element 190, and the gear 194 can match the gear 192. Therefore, the position of the gear 195 is indicative of the position of the valve element 190 and the arrangement of the valve opening 191 relative to the nozzle 158. A magnet attached to the upper gear 195 rotates relative to the open and close detections 220 (Figure 17) to indicate the positions jd ^^ i'ptq ·

MEXICAN INSTITUTE and^;i. &lt;·⁵'DE LA; ·· ΚΟ'. · 'ΕΓΑύ i-; ·. · Closed, respectively, of the filling valve 180. inoustwal

In Figure 12, there is shown a schematic cross sectional diagram of the lower end of the powder supply module 54, between the powder inlet 130 and the supply nozzle 158. As shown, the supply hopper 156 can be considered to be it has 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 duct

154.

The feed stem 160 may include a shaft 170 in the form of a rod extending axially through the supply hopper 156. The feed stem 160 further includes one or more feed elements fixed to the shaft 170. The feed elements Feeds move the powder from the powder inlet 130 to the supply nozzle 158 in a controlled manner. In the Figure modality of the Figure

12, the feed stem 160 includes a powder bed preparation element 160 in the powder bed preparation zone 156a, a powder bed compression element 165 in the powder bed compression zone 165b and an element of download 166 in the download area: IMPIf

165c. Examples of power supplies

IN DU ¿'ΓR. i Λ L describe below.

In Figures 13A and 13B, one embodiment of the feed stem 160 is shown. In the feed stem embodiments described herein, the powder bed preparation element 164 and the powder bed compression element 165 are implemented as a helical open space frame, including a plurality of spaced masts 172 mounted to axis 170 and one or more cables attached to masts 172 and axis 170. The masts 172 can extend radially from the axis 170 in the cylindrical conduit 152 and a tapered conduit 154. The masts 172 can extend almost to the inner wall of the hopper 156 without contacting the inner wall. The masts 172 in the tapered conduit 154 vary in length to coincide with the tapered inner wall of the tapered conduit 154. The masts 172 are mounted to shaft 170 in different radial directions. In a preferred embodiment, the ends of the masts

172 define a double helix.

In the embodiment of Figures 13A and 13B, a feed stem 160 includes ten masts. In this example, adjacent masts are spaced along axis 170 in 0.32-centimeter intervals, and each mast is rotated 45 degrees relative to the adjacent mast, except for the last two masts at the bottom of axis 170, the which are rotated 22.5 degrees. The diameter of the mast can be the preferred chipboard size, in the order of 0.064 to 0.19 centimeters. The mast material can be stainless steel or other, m

<img file="MX339072B_D0030.tif" />

^: MEXICAN INSTITUTE

PROPERTY Structurally rigid which is resistant to corrosion, such as'WéW, ceramic, plastic and the like. The feed stem can be made of 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 exterior surface. Too many masts cause dust to compact with stem rotation, while too few masts will not support the double helix configuration. The spacing between the masts and the angle between the adjacent masts can be inversely proportional to the number of masts used.

As noted above, feed stem 160 includes cables attached to masts 172. In the embodiment of Figures 13A and 13B, the cables define a double helix 174, a first chevron 176, and a second chevron 178. As shown, double helix 174 includes a helix cable 174a at or near one end of each mast 172 and a helix cable 174b at or near the opposite end of each mast 172. Each propeller cable 174a, 174b progresses downward from mast to mast in a clockwise direction as viewed downward from the stem trigger 162.

The first chevron 176 can include a first chevron cable 176a fixed to the masts 172 in a first separation from the axis 170, and a second chevron 178 can include a second chevron cable 178a fixed to

<img file="MX339072B_D0031.tif" />

masts 172 in a second separation from axis 170. Ϊ chevron 176a passes through hole 176b on axis 170 ^^ 30 ^^ 10 ^ ¾¾ chevron cable 178a passes through hole 178b on axis 170 It will be understood that the propeller cables and chevron cables do not necessarily attach to all masts on feed rod 160. In particular, the first chevron cable 176 is attached to the first mast (the uppermost mast), and the fifth mast. The second chevron 178a cable is fixed to the third mast and the seventh mast. The first and second chevrons may be 90 ° apart from each other.

In the embodiment of Figures 13A and 13B, the propeller cables and chevron cables are threaded through holes in the respective masts and are attached to each end. The propeller cables are located at or near the ends of the masts and the chevron cables are located at the desired clearances from axis 170.

Holes in masts 172 can be tool drilled, laser drilled, or EDM drilled at angles that prevent significant cable bending. Therefore, the holes in each mast are roughly aligned with the adjacent masts. This arrangement allows the cables to slide through the holes more or less freely, so that the powder loading forces are distributed over the entire length of the cable, thereby reducing the concentration of stress that might be produced a break up. In other embodiments, the cables can be attached to the masts, such as by laser beam welding, for example. In this example, Alo! (tebJesu

MEXICAN INSTITUTE

OF PROPERTY Ό

INDUSTRIAL propeller and chevron cables have a diameter of 0.020 centimeters.

Double propeller 174 can be formed by tying the outer ends of helically mounted masts 172 with propeller cables

174a and 174b. Wiring the masts 172 over both outer ends creates a double helix wire pattern. The double helix cable pattern performs three main functions. First, the perimeter wire inhibits compressed powders from adhering to conduit walls, particularly tapered conduit walls 154. Second, when the stem 160 is rotated clockwise (from the actuator shaft facing downward), the double helix raises dust at the duct wall interface and further reduces it in the range preferred agglomerate flowability size. Third, when the stem 160 is rotated counterclockwise, the double helix feeds the powder by volume down the axis 170 as well as along the chevron cable free paths and within the supply nozzle 158. Additionally, this rotary volume powder feeding operation tends to break the compressed powder discs, which form horizontally between the rotating masts 172.

Feed stem 160 uses a helical open-space frame that includes shaft 170 as a central support, masts 172 as structural cross members which form a helical pattern with a tapered bottom end geometry in fodpa ^ Aruca J.

^r MEXICAN INSTITUTE ..ü; · DE LA PRO? ID.) AL&gt; ' ^s and the cables that form the double helix 174 and first and second oheurons ^ W 'and 178, as previously described. The inverted conical shape changes the “masts from a larger diameter conduit to a smaller diameter powder discharge nozzle. The cables are attached to the masts to reduce the effects of volume dust compression and promote the flow of the chipboard paste. Feed Stem 160 has the ability to transport highly cohesive powders with microgram delivery precision, while controlling the trend for volume powder compaction. Powder compaction leads to jamming of powder compression, and thus clogs the delivery device. The helical open space frame provides an optimal volume powder transport element, which has the precision transport and delivery capabilities of all types of free flowing to highly cohesive powder morphologies. This capability is achieved by allowing only a minor portion of the helical mechanical forces to be directed downward into the powder bed by volume, thereby controlling the compression effects adequately for the individual characteristics of the powder being delivered. Due to this compression control, it is possible to transport cohesive powders from a large diameter conduit to a smaller one in an effective way.

Shaft 170 forms a central drive shaft of feed stem 160. Shaft 170 supports masts 172, double helix 174, and first and second chevrons 176 and 178, which, in turn, transp &amp; ^ MkoEO

MEXICAN INSTITUTE ~ X '.

FROM THE? ROHcD&gt; D,_{&gt; &lt;fc} per volume for precision delivery. The central drive shaft allows^{TO THE}fine powders flow along its smooth surface to supply nozzle 158.

The masts 172 are structural cross members that break the agglomerated bed of compacted powder. The 172 masts also support the propeller and chevron cables. Additionally, masts 172 provide the helical spiral mechanism necessary to transport the powder bed by volume in a low, controlled compression form.

Chevron cables 176a and 178a provide cut patterns within the volume powder bed. The cables are located to reduce compacted dust and temporarily open a free path within the powder bed that allows minute amounts of powder agglomerates to flow down through the powder bed by gravity.

Additionally, chevron cables serve the volume powder disk that forms between masts 172. These discs are created by progressive compaction forces and form suspended aggregate powder structures. By means of the cutting discs, preferably in medium coverage, the discs become structurally unstable and begin to break and flow downwards, driven by the mechanical forces of the helically inclined masts 172.

The discharge element 166 (Figure 12) is profiled and located to break a powder compression disk located in the supply nozzle 158. The powder disk is formed when feed JBAlálKilá 180 is closed and the stem 160 performs the operations * ' classify and clean dust by volume. Without the discharge element 166 to dislodge and shrink the disc, the disc could either occlude the nozzle and could fall into the cartridge when opening the valve, possibly causing the cartridge to overfill. The dust disk has a greater tendency to block the nozzle when the ambient humidity is above 50 percent.

Modes of the discharge element 166 are shown in Figures 13A-13B, 14A-14F and 15A-15D. Each of the modalities uses the above described helical mast and cable open space frame, although it uses different discharge elements. The powder is induced to fall into the powder bed preparation zone 156a by rotating the helical open space frame described above.

The outer helical cables break the attractive forces between the powder and the wall of the cylindrical duct and lift and aerate the powder bed when they are rotated in the reverse direction. Chevron cables cut and further reduce the dust bed as the helical space frame rotates. The powder bed preparation zone 165a improves the flow capacity of the powder bed as it enters the tapered conduit of the dust bed compression zone 156b. Powder flowability is enhanced by the ability of the helical open space frame to form natural agglomerates that allow powder to flow fe w

when it is induced by the forces of the api space frame

<img file="MX339072B_D0032.tif" />

-OY

ISTitíTf ΓΓΜΤΧ'ΙΓΛΤ. or

FROM LAPF.CHeOAD! Nl; 'JSTÁÍa !.

In the powder bed compression zone 156b, the agglomerated powder date experiences compression due to the reduction in volume of the tapered conduit. The compression zone stably increases the consolidation of the powder bed, while the masts and cables continue to reduce and ventilate the powder bed. In the discharge zone 156c, the powder agglomerate groups are further reduced and discharged through the nozzle 158. The discharge element controls the dust reduction and supply characteristics. Improper dust reduction control causes the discharge port to occlude. Inadequate powder reduction control also inhibits powder delivery within a specified time limit without exceeding the dosage limit. The discharge element determines the final powder supply flow rate and the consistency of the powder agglomerate.

In the embodiment of Figures 13A-13B, the discharge element 166 is configured as a modified mast 181. The two sides 181a and 181b of the modified mast 181 extend downward by a half turn of the propeller counterclockwise. , thus forming a double helix. The modified 181 double propeller mast and 174 double propeller have opposite inclinations. In other embodiments, one side of the modified mast is rotated upward in a helical fashion. The modified mast can use a propeller clockwise or counterclockwise. In some modalities,

<img file="MX339072B_D0033.tif" />

·^: ΙΜΡΙ The modified mast can be formed with a U-nverWá O -cemQ shape forma. OF THE FR.Í'FlEDAD t, IND'JS fftiAL a form of S. The form of U works improvement for the free-flowing powders, —imwwTiimiTfi ιτ »» «ι · ι wi&gt;» »i while the form of S performs best for cohesive powders. In the U-shape, both sides of the modified mast are rotated towards the supply nozzle. In the S-shape, one side of the modified mast rotates toward the supply nozzle and the other side rotates upward.

The modified double helix mast 181 of Figures 13A-13B, functions as a rotating bias element within the lower end of the tapered conduit. The modified Mast Reverse Tilt geometry adds dust lift and aeration to control powder delivery and improve powder consistency. The reverse tilt geometry also drives the powder into the nozzle during the sort cycle. This creates an initial 2 to 4 milligram powder discharge at the start of the supply cycle and allows more time for filling at the end.

Iii

Another embodiment of feed stem 160 is shown in Figures 14A-14F. In the embodiment of Figures 14A-14F, the discharge element 166 is implemented as a roller pin 183 mounted to the shaft 170 by a support element 185 having an inverted U-shape.

In the embodiment of Figures 14A-14F, an optional multi-slot baffle disk 189 may be located in the upper portion of the tapered conduit 154 and is attached to the lower housing section 150a.

. IMPI

Powder Supply Module 54 includes additional FEIT ^ f ^ '^ * INDUSTRIAL Orifice Element 187 mounted on the lower end of the tapered conduit

154. Hole element 187 may have one or more slot-shaped holes. In an embodiment shown in Figure 14D, a hole element

187a includes two slot-shaped holes that intersect to form a cross. In other embodiments, the hole elements 187b and 187c include intersecting slot-shaped holes as shown in Figures 14E and 14F. The holes can be relatively wide, as shown in Figure 14E, or relatively narrow, as shown in Figure 14F. Feed stem 160 is positioned such that roll pin 183 is separated from orifice member 187 by spacing less than the size of the natural chipboard. During operation, pin 183 rotates relative to orifice element 187, causing powder to be discharged through the orifices into orifice element 187.

Deflector disk 189 can be used to control the rate of advance of the powder bed and further reduce powder agglomerates as they enter the tapered conduit. In discharge zone 156c, the powder agglomerate groups are reduced and subsequently extruded by the rotating roller pin 183 through the holes in the hole element 187. The mechanism including support member 185, roller pin 183, and orifice member 187 controls the dust reduction and delivery characteristics. The reduction control

Inadequate dust causes the discharge port to occlude. He4á ^ rolcde^r ' OF THE PROPERTY

INDUSTRIAL inadequate dust reduction also inhibits the supply of powder within a specified time limit without exceeding the dosage limit. Support member 185 and roller pin 183 determine the final powder supply flow rate and the consistency of the powder agglomerate. The mechanism including support member 185, roller pin 183, and orifice member 187 can be configured to provide optimum powder flow and chip size for a particular powder morphology. The support member 185 tracks in a perimeter groove of the lower housing section 150a to automatically center the feed stem 160. Roller pin 183 combined with hole element 187 produces a supply of low force powder agglomerate. Orifice member 187 provides a powder agglomerate consistency within a narrower agglomerate size range.

A further embodiment of feed stem 160 is illustrated in Figures 15A-15D. Discharge element 166 is implemented as helical worm blades 240 and 242 fixed to shaft 170. Each worm blade 240, 242 has approximately one-half turn around shaft 170. The axial length of worm blades 240 and 242 they may be approximately half the axial length of the tapered conduit 145. As shown, the feed stem of Figures 15A-15D uses fewer masts than the modalities of Figures 13A-13B, and the propeller cables and chevron cables can be attached to the

<img file="MX339072B_D0034.tif" />

upper edges of worm blades 240 and 242. The auger screw 240, 242 and double helix 174 may have opposite inclinations.

OF PROPERTY C ** · ^ INDUSTRIAL

The powder supply module 54 shown in the Figures

15A-15D further includes a hole element 244 mounted on the upper end of the tapered conduit 154. In the embodiment of Figures 15A-15D, the hole element 244 has an inverted conical shape and is provided with a plurality of holes 244a for the discharge of powder through the nozzle 158. Additionally, the lower edges of the worm blades 240 and 242 are angled to match the inverted conical hole element 244. A bearing 246 mounted on the lower end of shaft 170 couples an aperture in bore element 244 and establishes a desired gap between worm blades 240, 242 and bore element 244. Bearing 246 may be a jewel material, such as a ruby ​​or sapphire, which is not contaminating the supplied drug powder. During operation, the worm blades 240 and 242 rotate relative to the orifice element 244, causing dust to be discharged through the orifices into the orifice element 244. In other embodiments, the orifice element may be flat, as shown in Figures 14D20 14F, and the bottom edges of the worm blades 240 and 242 are flat to match the hole element.

This mode rotates opposite to the feed rods shown in Figures 13A-13B and 14A-14F. In the discharge zone 156c, the powder agglomerates are made to flow through the blades of the Jo ^ ilJp ^ pjjn

IM fi with reverse inclination and subsequently extruded and granulated ^ Ltíiediartte

INDUSTRIAL the worm screw tip rotates through the holes in the hole element 244. The mechanism of the worm blades and the hole element control the dust reduction and delivery characteristics. Improper dust reduction control causes the discharge port to occlude. Inadequate dust reduction control also inhibits delivery within a specified time limit without exceeding the dosage limit. The worm gear mechanism 240, 242 and orifice element 244 has the ability to compensate for the variability of the powder bed fluid conversion head height, thereby reducing the sensitivity of the delivery procedure to conditions of dust bed head. The half turn of the double helix of the worm blades isolates the forces of the vertical fluid conversion bed from the powder at the nozzle, thereby eliminating force vectors that tend to pack the powder into the nozzle. The mechanism of the worm blades 240, 242 and orifice element 244 can be configured to provide optimum monotonic powder chipboard sizes. The mechanism provides a powdery chipboard consistency within a narrower chipboard size range. Bearing 246 provides alignment and support of the worm gear, while maintaining the thickness of the worm dust to hole diaphragm.

<img file="MX339072B_D0035.tif" />

In some modalities, the Mexican dec ^ gj ^^ | s ihstiti'Tó element is mounted in a hole in the tip of the shaft 170. In other modalities, the discharge element 166 is implemented on a point. '”Remove from shaft 170. For example, a double helix discharge member 5 may be formed on a removable tip that is press fit within the end of shaft 170. The removable tip can be changed to accommodate different powder morphologies.

The following approach to the operation of the powder supply module 54 refers to the sorting operations and the 10 supply operations for the modalities of Figures 13A-13B and 14A-14F. Sorting is an operation to clean and recondition a powder bed into a matrix of preferred chipboard size, uniformly aerated, thereby providing greater flow capacity characteristics for volume powder transport. The preferred chip size is the natural, stable size of cohesive powder pellets created by a powder bed dropping operation and is normally within the range of 0.64 centimeters to 0.20 centimeters in spherical diameter. Powder bed sorting can be done in either the down feed or lift modes. However, cohesive powders prefer uplink classification to achieve optimal aeration and improved flowability. Delivery is an operation to transport powder in dry volume in a "dusting" form, which falls under the force of gravity without compression, as a preferred agglomerated matrix, discharged from a JeJ ^ / ^ pjiJé¡¡ nozzle

INSTITUTO MEXICANO 'supplied in a cartridge. The delivery and supply apparatus described herein has the ability to operate colT aylüiiitíi dtlus eir powder in an interval of 0.02 centimeters to 0.20 centimeters in spherical diameter, although it is not limited to this interval.

Feed stem 160 is rotated in a clockwise direction as viewed from the top of supply module 54 to rake clean, clean and aerate the powder bed by volume. The clockwise rotation raises the dust due to an upward flow vector created by the double helix. In this operation, the stem can be seen as a screw, held vertically in its cap, spinning in the powder. The double propeller scrapes the walls of the duct and also moves the chipboards outside towards the center of the supply hopper. As the stem rotates, the masts force the large chipboards to break evenly. This aerates the powder bed by volume, creating better bed consistency.

To supply the powder, the stem 160 is preferably rotated in a counterclockwise direction. Masts 172 and chevrons 176, 178 break the powder bed and open a free path for powder to flow along axis 170. Double helix 174 adds a downward compression vector to drive powder down and through of the discharge nozzle 158. In other

<img file="MX339072B_D0036.tif" />

modalities, the stem 160 is rotated in one direction in sjn '

MEXICAN INSTITUTE _Λ ί * clock hands to supply the powder. However, the a ^ OrW ^ dc tends to be greater than the tendency to overfill than mnrhn for the supply of dust by clockwise rotation.

In the modalities described above, the propeller masts and cables have a clockwise configuration viewed from the top. It should be understood that the arrangement of the masts and cables of the power rod may be reversed within the scope of this invention. Therefore, the propeller masts and cables may have a counterclockwise configuration viewed from the top. In this configuration, the stem is preferably rotated in a clockwise direction to supply powder.

The following approach to the operation of the powder supply module 54 refers to the sorting operations and the supply operations for the modalities of Figures 15A-15D. Feed stem 160 is rotated in a counter-clockwise direction as viewed from the top of supply module 54 to clean the powder bed by volume and fill the worm. The double helix 174 adds a downward compression vector to drive the powder down and into the supply nozzle 158. At the same time, the worm blades 240, 242 supply force vectors upward over the powder to place the

<img file="MX339072B_D0037.tif" />

worm screw up in the upper bed for aeration. Institute_Mr'_XICANl

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To supply the powder, the feed stem 160 is preferably rotated in a clockwise direction. Clockwise rotation raises the upper bed dust due to an upward flow vector created by the double helix of the helical open space frame. In this operation, the upper stem can be seen as a screw, held vertically in its cap, which is rotated inside the powder. The double helix cuts the duct walls and also moves the exterior chipboards towards the center of the supply hopper. As the stem rotates, the masts force large agglomerates to break evenly. This aerates the powder bed by volume creating better bed consistency. Masts 172 and chevrons 176, 178 break the dust bed and open a free path for dust to flow along axis 170.

Dust on the worm gear when starting feed is forced through the nozzle by the downward force vectors of the worm gear. During delivery, the additional powder is supplied by the aerated powder falling from the upper bed.

In the modality described above, the propeller masts and cables have a clockwise configuration as seen from the top. It will be understood that the arrangement of the feedback stem masts and cables can be reversed within the scope of the present invention. Accordingly, the mast and what

INSTITUTO MF.X-CANO helix may have a counterclockwise configuration to the * 3κβ clock as seen from the top. In this configuration the stem is preferably rotated in a counterclockwise direction to supply the powder.

In Figure 17, a block diagram of a controller for a powder supply module 54 and the corresponding detection cell 114 is shown. Preferably, the powder supply device provides a redundant computing force strategically concentrated in the lowest level. Powder supply module 54 includes a supply controller 200 (Figure 17) on circuit board 183 (Figure 11). Supply controller 200 can include three processors. A processor is provided for each of the stem trigger and valve trigger 182, and a processor is used to control the status LEDs.

224 and the inputs of the optional analog detection. A control processor

210 it is located on a back plane of the detection module 34 as described below. The system uses a control processor 210 for each supply module 43 and its associated detection cell 114. Processor 210 controls communications between detection module 34 and supply module 54, as well as external communication. When the fill parameters and a "feed" command are provided, the control processor 210 provides the intelligence to read the detection cell and instructs the supply module triggers to fill the cartridge. The control processor 210 is also

VTX 'INSTITUTE OF THE PPOU

<img file="MX339072B_D0038.tif" />

L&gt; t LA t'r'sjr i ς L · \ D a supervisory processor 212 through a ϊ «υ ™ interface^ΑΈΙ supervisory processor 212 provides level control áTO flé TOAOS Ιδδ powder supply modules and detection cells.

The controller of Figure 17, except for the supervisory processor, is repeated for each supply module 54 and associated detection cell 114 in the system. In the example above of a 6 x 8 supply module layout, the system includes 48 controllers. This provision provides individual control and monitoring of the powder supply in each cartridge.

In one embodiment, the powder delivery module 54 is configured and controlled to accurately deliver 10.0 mg (milligrams) of powder in ten seconds. The average flow rate is 1.0 mg per second to an accuracy of +/- 0.3 mg, or 3 percent. The control circuit makes at least 20 decisions per second to fill in this flow rate. In other modes, the control circuit makes more or less than 20 decisions per second to achieve a desired precision. Feed stem geometry provides sufficient flow consistency to achieve this performance. The feed stem destroys dust clusters into small agglomerate particles. Mechanically fed chipboard pulp has flow characteristics that allow the powder to be suspended when the feed stem is stopped, with minimal excess powder, which could produce ^ cij ^ e ^ e ^ o ^, „.... 1 MEXICAN INSTITUTE V ”/ 'pi of cartridge filling.

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The control circuit can provide the following controls and functions.

one. The stem speed is variable from 0.1 revolutions per second to 5 revolutions per second at 50 different speeds.

2. The stem can be shaken while filling. During stirring, the stem alternately rotates clockwise when the stem rotates counterclockwise, such as, for example, the programmable stirring factor. A "shake less than weight" function couples the shaking motion when the fill weight is less than a selected weight. A "shake greater than weight" function couples the shaking motion when the fill weight is greater than the selected weight. A "shake between" function couples the shaking motion when the fill weight is between two selected weights. An agitation index is the rotation speed selected during agitation. A stirring weight is the weight selected to level or stop stirring, and a minimum stirring time at a selected stirring weight and can be selected. In some applications, agitation may not be used.

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

Four. The second circuit can weigh and measure the cell ai

i. INSTITUTO MEXICANO and start a powder supply cycle, and can stop the powder cycle.

5. The control circuit can clean the powder in the powder supply device with a sequence defined by cleaning time, stirring time and speed.

6. A new charge function initiates a clean / shake cycle that normally runs after closing the supply module with fresh powder. Cleaning time, stirring time and speed are specified.

7. Additional features include automatically opening and closing the fill valve during a fill cycle, automatically cleaning the powder every time the valve is closed, and automatically stirring the powder after cleaning every time you close the valve. valve.

8. A “stop steps” function sets a number of steps to reverse rotation of the feed stem after reaching a target weight. This tends to pull the powder flow back to avoid overfilling and depends on the type of powder morphology and ambient humidity conditions.

9. A speed control function forces the feed stem to travel at full speed until it reaches a selected fill weight. At this trigger point, proportional control begins to slow the stem speed in proportion to the target weight; ιμρϊ minus the actual weight. This method reduces the filling time tofsrsfj ^ íyfl^r fN'Dt'SI'PJ.AL

<img file="MX339072B_D0039.tif" />

nominal fill weight of 10 mg and a tolerance of +/- 3 percent, any fill weight between 10.3 and 9.7 mg is acceptable. Because an overfilled cartridge must be discarded, filling stops as soon as possible after it reaches the minimum weight in order to avoid possible overfilling. The minimum weight is set, for example, at 9.75 mg, which is slightly above the actual low limit of 9.70 mg. This is necessary because when the powder falls into the cartridge, peripheral forces such as inertia, aerodynamics, static, and magnetic field flux can produce temporary weight readings that are slightly greater than the actual powder weight. The reading sets the actual weight for a short time of a few tenths of a second. Setting the minimum weight to 0.05 mg above the actual low limit reduces the risk of a cartridge that has not been filled enough.

10. Parameters associated with the fill cycle include the proportional gain of the servo fill circuit, the integral gain of the servo fill circuit, which is activated, for example, 1.0 mg less than the target weight, and the maximum stem speed allowed during the fill cycle. Stem speed can be controlled by specifying a speed index between 0 and 50. The stem speed is in revolutions per minute as a function of the stem speed index, it has a characteristic that is relatively linear for low values ​​of the stem speed index and subsequently increases in shape.

<img file="MX339072B_D0040.tif" />

Dramatic majority at maximum stem speed. This finer control character at lower speeds than at speeds that the stem is displaced much faster, lasts for 70ρΰΓόΙό'η (the initial fill cycle to quickly fill the cartridge to 90 percent 5 of its fill weight. The stem is normally approximately 5 revolutions per second. Beyond speed, there is a risk of packing the powder so tightly that the delivery device would have to be removed and cleaned to restore the original powder flow characteristics.

An agitation factor controls reciprocation of the feed stem as it rotates, if agitation is allowed. In this mode, the ratio of forward rotation to reverse rotation is two. Therefore, the feed stem rotates 2n steps forward and n steps backward, based on the agitation factor value. Thus, for example, a stirring factor of 500 represents 1000 steps forward and 500 steps backward, while a stirring factor of 1 represents 2 steps forward and 1 step backward. In other modes, the ratio of forward rotation to reverse rotation can have a value different from two and / or can be programmed.

eleven. A servo fill time control function adjusts the maximum rate of stem speed in proportion to the time used at full speed during the last fill time. Time spent at full speed is a good indication of how well the powder is flowing. YES

<img file="MX339072B_D0041.tif" />

the real time at full speed is greater than the _entQpQes..the 'IMPIA control increases the maximum stem speed index 0arat &lt;agnf! 3QM $ i &lt;g' industrial filling speed. Conversely, if the real time at full speed is less than the setting, the maximum stem speed index is decreased to maintain consistent processing time. While filling as fast as possible is desired, there is a risk of packing the powder, occluding the delivery devices, or overfilling the cartridges.

The parameters of the powder supply module 54 are interrelated as follows. A control in which the greater limit is exceeded is available when the smallest particle agglomerate sizes are supplied inside the cartridge. Accelerating the stem increases flow rates even though the powder is compressed into large agglomerates. Large agglomerates increase flow, although overfilling is more likely in the last few seconds of filling. A large powder tank saves loading time of the delivery device, but compresses the powder into large agglomerates and requires further conditioning of the powder before filling. Agitation separates large agglomerates for more accurate filling, yet reduces the flow rate. Conditioning the powder before filling increases the filling consistency, although it adds an overall filling time.

An embodiment of a cartridge fill cycle is described with reference to Figures 18 and 19. The fill cycle is described

<img file="MX339072B_D0042.tif" />

referring to an example of filling the cartridge with one mg of Technosphere microparticles in 10 seconds. It was 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 the control processor 210 and the supply controller 200.

Supply control processors in conjunction with supervisory compute monitors, all of these control factors against fill weight values, read 20 times per second as supply devices are filling cartridges. These data, when compared against ideal delivery cycles, provide feedback to promote cohesion, improved flowability, powder consistency, drug efficacy in the patient, and overall quality control. It should be understood that weight values ​​can be read more or less than 20 times per second within the scope of the present invention.

Referring to Figure 18, the control parameters for the operation of the supply module can be set in step 250. For example, initially, agitation is set to "off".

Valve control parameters can be set such that cleaning is set for two seconds after a new powder charge, speed index is set to 44, automatic opening is set to “on” and automatic cleaning after closing it is placed in two seconds. The filled parameters can Jnj ^^ li ^ | n $ £ ·. '·.

MEXICAN INSTITUTE 8.8 mg setting at which proportional control starts ^ W ^ so ^ '-— target fill can be set to 10.0 mg, piupuiUunal gain --— · can be set to 1.0, integral gain can be set in

0.03, and the maximum speed index can be set to 41 (two revolutions per second). The stirring factor can be set to 50, and the servo fill time can be set to 10.0 seconds. A bipolar ionizer can be activated for the neutralized charge of the powder supply module and cartridge.

In step 254, the supply hopper 156 is filled with powder by the operation of the powder transport system 32. The powder is supplied to the disposal block 50 by the powder aerator 72. The powder is supplied through the channels in layout block 50 for each of the powder supply modules 54. When the excess powder passes through an arrangement block 50 and is detected by the fill level detection of the supply device in the suction collector 84, the charging of the supply modules 54 is completed, and the Powder transport is de-energized. Supply hopper 156 can be cleaned during the hopper fill cycle to remove large air holes and powder bed inconsistencies.

Hopper assembly 74 is filled by the operator or another automatic injection system. The flow assist mechanism rotates to break up the new compressed powder. The agglomeration rollers rotate to supply the large agglomerated powder to the dejde ^ yan ^ a jn jet aerator valve 72. A discharge valve level sensing'q ^ j ^ gge lar / i discharge valve is full to stop the rollers Hp aglnmArar.inn n blower assembly 70 rotates at approximately 3500 rpm for gas cycle through the system. The pneumatic broom rotates in preparation for powder delivery via the discharge valve. The bypass valve is set at 50% to facilitate both the transport of both dust and gas from the air stream.

The dump valve rotates in increments of 10 degrees per second to gradually blow dust into the air broom chambers. As the powder becomes available to the air broom, the fine agglomerates are transported to the riser tubes and into the supply fill chamber. Most of the filling occurs in the last positions of the delivery device at this time. After a discharge valve cycle is complete, the crossover valve rotates at 0% changing in increments of 10 degrees per second for phase in pressure of the maximum air broom. This transports all except the heaviest agglomerates within the supply chamber and fills the middle rows of the supply modules. Finally, the blower assembly 70 increases the speed to 8000 rpm to transport the rest of the dust from the pneumatic broom chamber to the first rows of the supply modules.

<img file="MX339072B_D0043.tif" />

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As these fill cycles continue,

MEXICAN INSTITUTE supplies are filled. The blower assembly 70 in combi ^ j ^^ ¿laQ ^ bypass valve still outside the weight of the iminictrn device g through Hp the supply modules by recovering the dust from high peaks, circulating the fine dust through the system and depositing the powder in the low pressure areas of the powder bed between the peaks.

In step 258, a cartridge is placed under supply nozzle 158 on the weight sensing cell. As described above, a cartridge tray is placed between the arrangement of the powder supply modules 54 and the detection module 34. In step 260, the cartridge is filled with the prescribed powder dose. The fill cycle is described below in connection with Figure 19. In step 262, the fill valve closes and the rotation of the feed stem stops.

At step 264, a determination is made so that, if the supply hopper requires new filling. If the supply hopper requires refilling, the procedure returns to step 254. IF the supply hopper does not require refilling, the procedure returns to step 256. In the present example, the supply hopper can be refilled after four doses of 10.0 mg. It should be understood that the new filling of the supply hopper may sink after more or less filling cycles of the cartridge, depending, for example, on the capacity of the supply hopper and the amount of powder supplied in each filling cycle.

The supply hopper is filled again

<img file="MX339072B_D0044.tif" />

step 254. If refilling is not required, the procedure continues with the fill cycle for the next cartridge in step 256. In the present example, the supply hopper contains enough powder for twenty 10.0 mg doses. In some embodiments, the filling procedure is independent of the weight of the powder in the supply hopper to create a dry powder fluid conversion head and aid in gravity induced powder flow. Without a proper fluid conversion head, the fill time increases beyond the fill time limit. Other techniques can be used to determine if fresh filling of supply hopper 156 is required. For example, if little or no powder is supplied during the cartridge fill cycle, it can be assumed that fresh filling of hopper is required supply 156.

A mode of the cartridge fill cycle is shown in the

Figure 19. An initial operation is to measure and weigh the cell in step 280. The measure and weigh operation subtracts the weight of the empty cartridge from the reading detection cell so that the detection cell is read at zero or near zero at the beginning of this filling cycle. The control circuit waits 0.5 seconds for the detection cell to complete its measurement and weighing cycle and proceeds with the fill operation if the detection cell reads less than 0.02 mg. Otherwise, the measurement and weight cycle is repeated.

In step 282, the fill valve 180 is opened. As described below, the fill valve opening may be slightly compensated from supply nozzle 158 pjr ^^ jpnjr \ consistent operation.

MEXICAN INSTITUTE OF PROPERTY

<img file="MX339072B_D0045.tif" />

In step 284, the feed stem is sertraü ^ gt ^ rr ^ ia 'counterclockwise direction for filling. 5 Normally, actual filling starts after about 2 seconds, the time it takes to sufficiently advance the powder and restarts the powder flow after cleaning. Initially, the feed stem is rotated at the full specified speed during setup of the supply module. The weight of the powder supplied in the cartridge is monitored during filling.

At step 286, a determination is made whether the current detected weight is greater than the selected weight at which proportional control was started. In the example of a 10 mg dose, the selected weight may be 8.8 mg. If the detected weight is not greater than the selected weight, the procedure returns to step 284 and the rotation of the feed stem continues at full speed. If the detected weight is greater than the selected weight, the speed stem 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. The speed of the stem is controlled according to:

New stem speed index = (Close

INSTITUTO MEXICANO V initial) * profit provides Maximum index) + (strategic gain elapsed). ---- In this mode, the control circuit sets the stem 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 previous example, the stem speed is reduced from the maximum index of 41 to an index of 20. Due to the nonlinearity of the index curve- speed, the actual stem speed is less than half of the initial speed. As noted above, the velocity-index curve is linear to zero where most of the control is required. The proportional gain value allows the amount of speed to change as an error function to be varied. The elapsed time is “on” when the desired detected weight is greater than the target weight minus 1.0 mg. The proportional error equation reduces stem speed based on a fixed ratio of actual to desired weight. There are times at very low speed, when approaching the target weight, that the stem speed is inadequate to produce the powder flow. If left alone, the fill cycle could run overtime and fail to complete the target weight. 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 speed of^v^ j ^ [rpéJo ^ Z ^

INSTITUTO MEXICANO forces the stem to rotate faster to overcome the sticking déiJOá'do . ^ 'T: ^ Referring again to the Figure- «4 © r” © * “- weigh—— current detected is compared to the minimum weight in step 290. If the current detected weight is less than the minimum weight, the stem speed servo control continues in step 288. If the current detected weight is equal to or greater than the minimum weight, the weight Current detected is compared to the maximum weight in step 292. If the current detected weight is greater than the maximum weight, the cartridge is determined to be overfilled in step

294. If the current detected weight is not greater than the maximum weight, the fill cycle is completed and the procedure returns to step 262 in Figure 18.

In step 262, the control circuit can adjust the servo. If the fill time was greater than 11 seconds, the control circuit can increase the maximum speed index by one. If the fill time was less than nine seconds, then the control circuit can decrease the maximum speed index by one. This control is intended to maintain a consistent fill time of 10 seconds.

Preferably, valve element 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, the valve element 190 is compensated in such a way that the opening of the valve 191 is compensated towards the closed position of the valve. The addition of valve element 190 is rotated in a direction where v &lt;

the valve to compensate for any hysteresis in the drive train. Therefore, for example, valve element 190 can be rotated clockwise to open the valve, and can be further rotated clockwise to close the valve. This operation reduces the risk of inconsistent filling or overfilling that may be the result of uncontrolled compensation between valve element 190 and tapered conduit 154 in the open position.

Any offset between valve opening 191 and tapered conduit 154 in the open position produces a small platform on top of valve element 190 that can collect dust. If valve opening 191 is pre-positioned relative to tapered conduit 154, any powder from the platform is discharged when the valve closes, potentially overfilling the cartridge. When valve opening 191 is positioned rearward relative to tapered conduit 154, the valve closes without discharging any dust from the platform. The powder is discharged when the valve for the next cartridge is opened, and the discharged powder is measured by the detection cell.

The powder delivery module 54 and its operation have been described in connection with the modalities for supplying a specified amount of Technosphere microparticles in a specified time. It will&gt;, * '* _Jz * understand that a variety of different supply structures and operating protocols can be used within Tá^Top ^^^ invention. For example, the feed stem can utilize different structures, such as different mast configurations, different cable configurations, and in some embodiments cables may not be required. Different numbers of propeller cables and chevron cables can be used. Different discharge elements can be used. The feed stem can use a different feed mechanism, such as a screw mechanism to supply the powder. Any fill valve mechanism can be used to control the powder supply. Regarding operation, any operation parameter that achieves the desired operation parameters can be used. For example, any suitable movement of the feed stem can be used, such as rotation, reciprocation, or vibration. The speed of movement can be fixed or variable, or a combination thereof. Stirring, proportional control, comprehensive control, and other control techniques can be used separately or in combination as needed. The detection module can be configured to supply the detected values ​​at any desired rate, within the capabilities of the detection module. In general, the powder supply module 54 could have a compact structure to allow mounting in an arrangement as described above and must be configured to supply a desired amount of powder in a specified time interval in response to a control circuit which receives the detected values ​​from a detection module! weight detection in the modality described above.

As shown in Figures 20 and 21, TiT ^ oduío de

<img file="MX339072B_D0046.tif" />

MEXICAN INSTITUTE,

FROM THE MCnCDA »

INDUSTRIAL '' «..You ?.

Detection 34 may include detection assemblies 110 mounted in detection housing 100. In the illustrated mode, each detection assembly 110 includes two detection cells 114. Detection assemblies 110 are mounted in detection housing 100, such that so that detection cells 114 are placed to weigh cartridges 20 in cartridge tray 22. In one embodiment, sensing cells 114 are mounted in a 6x8 arrangement, on one-inch centers. In this embodiment, 24 detection assemblies 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, where two detection cells are packed together. The mechanical weight sensing 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.

Detector housing 100 includes a detector placement plate 310, a detector enclosure 312, a detection tray 314, and a guide pin assembly 316. Placement plate 310 includes an opening arrangement that matches the positions of the cartridges in the cartridge tray 22 so that the xefcia®

INSTITUTO MEXICANO '/ c detection114 are precisely positioned with jálfós respes &lt;cartridges 20. The guide pin assembly 316 allows the Ja-plate-placement * 310 to be placed on the detection assemblies 110 without damaging the detection probes 112 o detection cells. Detection tray 314 may include a partition arrangement for placing detection assemblies 110 in detection module 34.

Detection module 34 further includes detection backplates 330 having connectors 332 for mating to electrical connectors 300 of detection assemblies 110. In the embodiment of Figures 20 and 21, detection module 34 includes two plates 330 rear, each having 12 connectors 332 to accommodate a total of 24 sensing assemblies 110. Each detection backplate 330 may include a control circuitry for processing signals from detection assemblies 110 and for communicating with powder supply modules 54 during cartridge filling operations.

Detection module 34 may be provided with an arrangement for cooling detection assemblies 110, which includes a detector cooling rack 340, detector cooling housing 342, and detector cooling manifolds 344 and 346. Cooling air can be directed through cooling manifolds 344 such that forced cooling air is supplied to the lower portion of detection module 34, which contains the circuit system ^ l ^ t ^ c ^ J ^ n the modality of Figures 20 and 21, the collectors of cooling {pT3 ^ ,; 5 $ n f '. INDUSTRIAL

<img file="MX339072B_D0047.tif" />

attached to the detection tray 314 and the cooling manifolds 346 are attached to the cooling housing 342. With this arrangement, the cooling air circulates through the detection tray 314 and subsequently down into the cooling housing 342, and it is expelled through the cooling manifolds 346. In another cooling arrangement, the cooling manifolds 346 are attached to the detection tray 314, such that cooling air is directed through the detection tray 314. Unused openings in the detection tray 314 may closed by cover plates 348. Each of the cooling manifolds 344 and 346 may include internal passages, which provide uniform air flow through the detection module. Additionally, 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, which provides an interface between the weight sensing cell and cartridge 20 is shown in Figure 22. Probe 112 includes a main body 360 that includes a post 362 that couples the detection cell, a head 364, and a cone 366 that collects dust and lost dust particles. Probe 112 additionally includes a powder skirt 370 that diverts dust and powder particles away from the detection cell and pins 372 to couple and support cartridge 20. The three pins 372 are ^ epa

<img file="MX339072B_D0048.tif" />

same way in 120 degree intervals and are designed^Dfié ^ i ^ n ^ 9si

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elastic shape and then return to their original positions. Additionally, the pins are designed to make a break in an overload condition to protect the detection cell. In the embodiment of Figure 22, pins 72 can be removed for pin height changes for different cartridge tray designs. The small cross-sectional area of ​​the pins reduces the aerodynamic effects of thermal currents, which can add deflection load forces for accurate microgram weight measurements.

A second embodiment of the weight detection probe, which provides an interface between the weight detection cell and the cartridge 20, is shown in Figure 23. A probe 112a includes a main body 380, which includes a post 382, a head 384 and a cone 386. The cone 386 collects dust and lost dust particles. A powder skirt 390 diverts dust and powder particles away from the detection cell. In the embodiment of Figure 23, probe 112a includes pins 392 that are integrally formed with head 384. Each of the pins

392 it is reinforced with a radial plate. This configuration adds structural rigidity to the vertically cantilevered lift pins. This configuration also reduces vibration and displacement at the pin tips, thereby damping the fingerboard effect.

In Figures 24 to 27 and 28A to 28C, ^ n ^ j ^ ippija powder aerator mode 72 is shown. A second powder mode 72 is shown in Figures 29 to 32. The powder aerator 72 includes .... ...

a manifold block 500 which defines a gas inlet 78, the powder inlet 70 and the powder outlet ports 82. As described above, the gas inlet 78 is connected by means of a tube 76 to the assembly of blower 70, hopper assembly 74 is mounted to powder inlet 80, and powder outlet ports 82 are connected to respective channels in disposition block 50. Powder aerator 72 can 10 include a pneumatic broom 510 to supply powder through riser tubes 512 to powder outlet ports 82 and a dump valve 520 to supply a quantity of powder from powder inlet 80 to the Pneumatic broom 510. In the embodiment of Figures 24 through 27 and 28A through 28C, four tubes 512 in manifold block 500 connect the pneumatic broom 510 15 to the powder outlet ports 82. The dust aerator 72 further includes a crossover valve 52, which directs the transport gas received through the gas inlet 78 to the air broom 510 and to a diverter manifold 526 in a desired proportion. The transport gas directed through the bypass manifold 526 is flowed through the 20 powder outlet ports 82 to the disposal block 50, such that it conveys the powder to the powder supply modules 54 mounted in each layout block channel 50.

<img file="MX339072B_D0049.tif" />

The pneumatic broom 510 includes a generally cylindrical aerator tube 530, which has a hollow interior and

<img file="MX339072B_D0050.tif" />

discharge nozzles 532. Aerator tube 530 is located in a hole in manifold block 400. Discharge nozzles 532 can be formed in a helical pattern on aerator tube 530 and can be approximately tangential with respect to a cylindrical surface of the tube aerator 530. Dividers 534 are spaced along aerator tube 530 and define annular chambers 542 corresponding to respective riser tubes 512. Additionally, the pneumatic broom 510 includes paddles 590 fixed to dividers 534 and spaced around annular chambers 5423. The combination of chipping nozzles 532 and paddles 590 provides effective transportation of a powder paste within a disposal block fifty. A flow director 536 attached to one end of aerator tube 530 includes blades to help break up dust clusters and to direct transport gas from cross valve 524 into the hollow interior of aerator tube 530. An aerator core 538 has a contour to help equalize transport gas flow through discharge nozzles 532. A motor 540 causes aerator tube 530 and flow director 536 to rotate within manifold block 500. The 540 motor can have a variable speed and rotates the pneumatic broom 510 at a relatively high speed, for example 3500 rpm, to transport a powder paste.

The discharge valve 520 includes a cylindrical core

MEXICAN INSTITUTE has diametrically opposite cavities 552. Core 550 is morifaíOiSSS ^J a hole in the manifold block 500 above the pneumatic broom 510 and is connected to a motor 554 for rotation about its central axis. Core 550 is placed by motor 554 with one of cavities 552 facing up toward powder inlet 80. Powder is supplied by hopper assembly 74 through powder inlet 80 such that it fills, or partially fills cavity 552. The core 550 is then rotated 180 °, causing the powder to be discharged into the annular chambers 542 around the aerator tube 530. The maximum amount of powder supplied in a single operation of the discharge valve 520 is defined by the volume from cavity 552.

Cross valve 524 includes a valve element 560 mounted in a hole in manifold block 500 and a valve actuator 562 to rotate valve element 560 about its center axis. Valve element 560 may be configured as a hollow cylinder having an inlet port 564 and outlet ports 566 and 568 at the selected circumferential positions. Ports 564, 566, and 568 can be provided with blades to block and break dust groups.

By proper adjustment of valve element 560, the transport grease received through gas inlet 78 can be directed in desired proportions through air brush 510 and bypass manifold 526. In one embodiment, the crossover valve 524 is adjusted during powder delivery to the disposition block mode, crossover valve 524 has a position of powder supply to disposition block 50.

The powder aerator 72 may additionally include a flow straightening device 570 and a profiled flow element 572 to help provide a uniform flow of the transport gas through each of the powder outlet ports 82. Each port Outlet 82 can be configured as a discharge cavity that coincides with the inlet end of one of channels 60a to 60h. Bypass manifold 526 supplies the transport gas to the top of each discharge cavity, and each riser tube 512 supplies the aerated powder upstream of the transport gas flow into the discharge cavity, as best shown in Figure 28A.

Powder aerator 72 serves as the interface between hopper assembly 74, array block 50, and blower assembly 70. Powder aerator 72 receives fresh powder from hopper assembly 74 and receives newly circulated powder. blower assembly 70. Fresh powder is received through discharge valve 520, and the newly circulated powder is received through gas inlet 78 and is distributed via crossover valve 524 to air broom 150 and dust collector. diversion 526 according to the position of the crossover valve 524.

The second modality of the 72 me dust aerator

Figures 29 to 32, is similar to the powder aerator shown in and 28A to 28C, except for the following. How best is Antas?

Figures 31 and 32, the pneumatic broom 510 also includes dividers

534a, which are spaced along the aerator tube 530 and define the annular chambers corresponding to the respective riser tubes in manifold block 500. Pneumatic broom 510 in the second embodiment does not include separate blades around the annular chambers. Additionally, the powder aerator of Figures 29 to 32 is provided with a motor 540a, which rotates the air broom 510 at a relatively low speed, for example, from 1 to 10 rpm, to transport a powder spray.

The components of the dust aerator 72 include the air broom 510, the dump valve 520 and the crossover valve 524.

Additionally, bypass manifold 526, flow element 572, and flow straightening devices 570 are used to equalize the gas flow within each channel of disposal block 50. Pneumatic broom 510, crossover valve 524, and The discharge valve 520 is motor operated and controlled by a system control computer.

The crossover valve 524 channels the incoming transport gas in two directions: inside the diverter manifold 526 and inside the pneumatic broom 510. The rotary cylindrical valve has longitudinal grooves to channel the flows while maintaining übaLp &amp; nnck

MEXICAN INSTITUTE OF PROPERTY relatively constant hydraulic, promoting in this way^NDa^L stable discharge.

The 510 air broom has several elements. The intake duct blades on flow director 536 change the direction of the incoming transport gas in a low-loss, efficient way, while creating an impact system that blocks and obliterates the agglomerates lost before the outlet nozzles occlude. downdraft 532. The tangential gas discharge nozzles 532, which preferably have a double helix configuration, are arranged along the length of the aerator tube 530. The pneumatic broom 510 is divided into four annular chambers 542. The drug powder that is supplied from the discharge valve 520 it is aerated in the annular chambers 542. The tangential discharge nozzles 532 effectively aerate and entrain drug powder from the chamber walls. Cross valve 524 allows two transport gas streams to be controlled in reverse, that is, one can be increased while the other is reduced. This control function allows the drug powder to be dropped into the annular chambers 542 to form the natural average chip size. The transport gas flow can then be steadily increased to transport the aerated powder paste to the riser tubes 512 and into the channels of the layout block 50, which fill the channels of the layout block in a process of deposition of j ^ particles^yes transport procedure takes advantage of the morfotog ^^^ t ^ lW ^

INtUSrWAt undesirable powders that naturally agglomerate and coerce them into an agglomerated state that allows them to be rheumatically transported effectively.

The riser tubes 512 intersect the discharge cavity of each outlet port 82. At this juncture, the horizontal transport gas deflects the emerging dust paste that is rising and causes it to move in a downdraft within the channels of the block of disposal 50. This procedure creates the conditions for the controlled particle deposition procedure.

Powder aerator 72 receives a known amount of powder from hopper assembly 74. Dust is collected in discharge valve 520. Discharge valve 520 isolates the transport gas from hopper assembly 74. Additionally, the valve Discharge 520, transfers the powder through this gas safety lock and into the 510 air broom. Discharge valve 520 may have an optional ability to perform a coarse weight measurement of the initial drug powder deposited into the system from the hopper assembly 74. The weight measurement can be performed using a load cell placed in cavity 552 of the discharge valve 520. The coarse weight measurement can be used as a feedback control for hopper assembly 74 as well as additional data for volume dust delivery mo.

<img file="MX339072B_D0051.tif" />

Pneumatic broom 510 fluidizes, disperses, and admits drug powders into a transport gas in annular chambers 542.

Chambers 542 are supplied with a transport gas by multiple tangential discharge nozzles 532 in a helical configuration. The helical configuration can include one or more propellers, such as a double helix. Additionally, the pneumatic broom 510 includes gas channeling blades in the flow director 536 that efficiently direct the gas within the aerator tube 530 and act as impact devices to reduce large agglomerates before they reach the discharge nozzles 532.

The crossover valve 524 divides the incoming transport gas between the air broom 510 and the diverter manifold 526. The crossover valve 524 is configured to inhibit any swirling vertex flow conditions within a compact design. The valve has slot flow ports to optimize and control gas flow. The crossover valve is used to control the transport of the agglomerated powder paste, aerated within channels 60a to 60h of disposal block 50.

The profiled flow element 572 is placed inside the bypass manifold 526 to improve the flow geometry of the conduit. As bypass gas flows from crossover valve 524 and into bypass manifold 526, it is preferable to create isocin flow patterns.

<img file="MX339072B_D0052.tif" />

inhibit the formation of fhjjc stagnation zone conditions or eddy flow.

Flow straightening devices 570 include vanes, which regulate gas flow by restriction and straightened gas flow as they are discharged into discharge cavity 580. By altering the spacing between the vanes, it is possible to achieve uniform flow through each of the channels 60a to 60h of the layout block 50.

A first embodiment of the hopper assembly 74 is shown in Figures 33 and 34. As shown in Figures 33 and 34, the hopper assembly 74 includes a hopper body 600, which defines a dust container 610, to maintain a powder supply, and a powder outlet 612, which couples the powder inlet 80 of the powder aerator 72. The hopper assembly

74 may be provided with a hinged cover 614, and a flow assist mechanism 620. The flow assist mechanism 620 may Include a helical coil 622 placed within the dust container 610 and a motor 624 to rotate the coil 622. The Hopper assembly 74 may additionally include a granulating device 630 in a lower portion of powder container 610. The granulating device 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

<img file="MX339072B_D0053.tif" />

plurality of pins 640 extending radially respective d. In one embodiment, the locations of the pins 640 on each of the rollers 632 and 636 define one or more helical patterns. Additionally, the agglomeration rollers 632 and 636 can have hollow centers and can be provided with air holes that connect to the hollow centers. The gas connectors 650 at the ends of the rollers 632 and 636 can be connected to a source of pressurized air. The air flow through the holes in the rollers 632 and 636 helps to aerate the powder that is being supplied to the system.

During operation, after the powder container 610 has been filled to the level of the hopper level detector, the first and second agglomeration rollers 632 and 636 rotate, causing dust agglomeration and discharge of the agglomerated powder through from 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 rollers 632 and 636 rotating toward each other. However, the operation is not limited in this regard. Agglomeration rollers 632 and 636 can be rotated continuously, reciprocating, or a combination of continuous and reciprocating, and can be reversed. The rotation protocol depends on the morphology of the powder. The granulating device 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 modality of the hopper assembly 74 is rjuj ^ fajíi J 6

MEXICAN INSTITUTE 1 OF THE PROPERTY Figures 35 and 36. The hopper assembly of Figures 35 and 36 is slmílárat^{TO THE}hopper assembly of Figures 33 and 34, except as follows'. tIT'SI— hopper assembly of Figures 35 and 36, the flow assist mechanism is not used. Additionally, the granulation device 630 is implemented with the agglomeration rollers 632a and 636a, each of which is provided with a plurality of separate discs 660 mounted to the axes of the respective rollers. The discs 660 can be provided with notches 662, which aid the downward movement of the powder through the container 610. The roller discs 632a can be intermeshed with the roller discs 636a.

The bulk powder can be introduced into the powder container 610 through the opening in the upper part of the hopper body 600 with the cover 614 open. In the second modality of the hopper assembly

74 shown in Figures 35 and 36, a powder paste can be introduced into the powder container 610 through an accessory 670 on an angled portion of the hopper body 600. The accessories 672 mounted on the upper portion of the hopper body 600 they provide an extraction for the transport gas introduced through accessory 670 with the powder paste.

Hopper assembly 74 is the main powder reservoir and is the stage at which powder is introduced into powder supply system 32. Hopper assembly 74 is designed for highly cohesive powders, such as Technosphere microparticles. The 630 granulation device produces agglomerates of powder in a range

MEXICAN INSTITUTE OF PROPERTY finite. This preconditioning improves aeration of the powder 'and' TSS '¹intake characteristics, creating a mix of agTótYlératJdJe ™ powder - uniform multi-size. Additionally, the powder granulation process aerates and mixes the powder that is normally compressed by gravity when it is stacked inside the powder container 610.

In the middle region of the powder container 610, the flow assist mechanism 620 forces the powder to avalanche downward or fall into the granulation devices 630. The need for the flow assist mechanism 620 is contingent on the level of cohesive capacity of the powder. The effect can become more evident 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 Figures 37 and 38. As shown in Figures 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 assembly 706 and an impeller 708 mounted in a blower housing 710. The blower housing 710 has a discharge port 7120 to supply the transport gas through tube 76 to the dust aerator 72. The adapted suction collector 84 is mounted to the lower end of the blower housing 710. As described above, the transport gas is circulated

<img file="MX339072B_D0054.tif" />

again from disposition block 50 to blower assembly 70. Suction manifold 84 includes inlet ports 714a, 714b,

FROM INDUSTRIAL PROPERTY which are connected to respective channels in disposal block 50. Cyclone separator 702 includes a cylindrical housing section 84a of suction manifold 84, which is mounted to blower housing 710 and a cyclone container 720 mounted below suction manifold 84. The cyclone separator 702, which serves as a gas-particle separation device, receives the powder agglomerates that pass through the disposal block 50 without being supplied to the powder supply modules 54.

A porous induction rod 724 is located within the center of cyclone vessel 720 and is connected to a gas conditioning system 730, as shown in Figure 41, and is described below. The gas conditioning system 730 supplies conditioned gas through a 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 pulsed by a valve within the closed loop system from a source, such as a source of pure water vapor or a source of steam. The relative humidity of the circuit is controlled by detecting the gas in a small bypass circuit that is connected to a detection chamber for temperature, pressure and relative humidity detections. The bypass circuit may be located between the discharge port of the blow "^ lc ^ | .1 | and the adapted suction manifold 84. In additional modes,

INDUSTRIAL pulsed valve can be configured as a dual door system that allows a quantity of gas conditioning to be pulsed into the closed circuit system, and a compensating or equal amount of transport gas to be discharged outside of the closed circuit system .

A second embodiment of the blower assembly 70 is shown in Figures 39 and 40. The blower assembly of Figures 39 and 40 is similar to the blower assembly of Figures 38 and 39, except as follows. In the blower assembly of Figures 39 and 40, the cyclone separator is not used. Instead, a blade separator 750 is placed in the housing section 84a of the suction manifold 84 on the suction side of the blower. The blade separator 750, which serves as a gas-particle separation device, has a cylindrical configuration of blades 752 separated by vertical grooves for separation of the heavy particles from the transport gas. The aspe 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 blade separator 750 removes the heavier particles, while the lighter particles and the transport gas move into the blade separator 750 and then to the impeller 708. The induction rod 724 is placed inside the

ÍBW

MEXICAN INSTITUTE

OF INDUSTRIAL PROPERTY blade separator 750 in the second form of assembly

70. ·

<img file="MX339072B_D0055.tif" />

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 recirculating gas circuit to inhibit the particles from occluding the discharge nozzles of the dust aerator 532. This is accomplished by the cyclone separator 702, the blade separator, or any other gas-particle separation device.

Powder transport system 32 is configured with a secondary process gas circuit between gas-particle separation device and discharge port 712 of blower 700. This control circuit can introduce secondary gas conditioning to regulate the environmental parameters of the primary recirculating transport gas, such as temperature, pressure, relative humidity, electrostatic levels, ion charge concentrations, gas element mixtures, production of fine particles spray, etc.

Closed loop powder delivery system 32 is Powered by blower assembly 70, which is a hybrid of Impulse blower blower coupled to the outlet side of a cyclone separator or other gas-particle separation device. The blower assembly 70 forms the primary cause of the transport gas and includes a self-cleaning powder agglomerate filtration system. Additionally, the transport gas is conditioned by the secondary process circuit, which controls the properties of the primary processing circuit. These two circuits are encaidtf ^ ffiOfó &amp; AS

INDUSTRIAL within blower assembly 70. Blower assembly 70 includes an impeller 708, which has a wheel vane configuration with curves wound between each impeller blade. The wheel vane impeller configuration produces dynamic shock waves in the form of a pressure pulse downcomer 76 and within the powder aerator 72. These check waves assist in the breakdown, aeration, and dispersion of the compressed drug powder .

The blower has variable speed capacity and is Powered by the 704 blower motor. When the 704 motor is operated beyond normal operating speeds, the transport gas acts as a recirculating gas scrubber that helps remove dust. residual from closed circuit duct channels.

A schematic block diagram of the gas conditioning system 730 is shown in Figure 41. The gas conditioning system 730 includes a secondary gas treatment circuit that is different from the closed circuit system for recirculation of the transport gas and powder supply to disposal block 50. A portion of the recirculating transport gas is diverted to the secondary gas treatment circuit near the discharge port 712 of the blower assembly 70. The conditioned gas is reintroduced to the recirculating transport gas circuit through the induction rod.

724. The 730 gas conditioning system includes a fWHPF

INSTITUTO MEXICANO vapor 800, coupled to a 802 water supply, to generate rapid steam, an 810 evaporator to reduce the relative humidity, valves 812 and 814 to select the steam generator 800 or the evaporator 810, filters 820 and 822.

The relative humidity of the transport gas can be measured by a detector, such as the detection chamber described below, positioned to detect the transport gas. When the relative humidity of the transport gas will be increased, valves 812 and 814 are connected to steam generator 800. Steam generator 800 includes a bubble generator and instant evaporator heaters to quickly produce water vapor. The bypass transport gas in the secondary circuit passes through filter 820, steam generator 800, and filter 822, thereby returning the gas with increased relative humidity to induction rod 724. When the relative humidity of the transportation is to be decreased, valves 812 and 814 connect to evaporator 810. The diverted transport gas in the secondary circuit passes through filter 820, evaporator 810, and filter 822, therefore returns the 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 cyclone container 720. The conditioned gas is introduced into the container at the end of induction rod 724. Induction rod 724 is manufactured. from a sintered metal

INSTITUTO MEXICANO porous plastic, which allows the conditioned gas to be uniformly dissolved within the recirculating transport gas if it produces water drops or slow flow conditions. The process treatment gas circuit is equalized by a return takeoff branch line on the discharge side of the blower 700. A portion of the cyclone separator 720 or the housing section 84a may be made from glass for visual inspection of the collected drug powders. If the collected dust can be recovered, it can be reintroduced into hopper assembly 74, or it can be discarded.

Control of the humidification of the powder during the operation of the powder transport system is complicated by the fact that the exposed surface area of ​​the powder changes during the transport procedure. The powder is initially prepared in the agglomerated state. However, as the dust breaks up and disperses during gas transportation, its exposed surface area is increased significantly, in turn, causing rapid moisture usage. In order for a humidification procedure to be maintained with and to control this rapid dehydration of the transport gas circuit, the gas treatment system must have the ability of rapid forced hydration.

Cyclone Separator 702 has an integral matched intake manifold that arises within the cyclone body with minimal hydraulic loss. The blower assembly has a large flow range and can serve as a system dust scrubber. The so | Ja ^^ é¡íáj [í MEXICAN PROPERTY INSTITUTE equipped with an impeller similar to a wheel paddle that has surface §^{TO THE}-curves rolled between each pallet to transport '^ Ticiei ^ enos ”^' ™ '^' finer powdered aerosols and to inhibit new agglomeration or caking of the powder. The paddlewheel-like impeller directs dynamic shock waves into the powder aerator 72 to help form the fluid from the drug powders. Blower assembly 70 includes a gas conditioning system where a secondary gas treatment circuit is introduced into the unit through induction rod 724 into the cyclone vessel. The gas conditioning system can control many gas parameters, such as relative humidity and temperature, static ion control, fine particle production, trace element production, gas catalyst activation, sterilization control of gas / light etc.

An embodiment of a detection chamber 850 to detect the condition of the transport gas in the powder transport system is shown in Figures 42 and 43. The transport gas, with the dust removed as far as practical, is circulated at through the 850 detection chamber in parallel with the dust transport system. Detection chamber 850 contains detectors for detecting transport gas parameters, such as relative humidity and temperature, to allow transport of gas conditioning as described above.

Detection chamber 850 receives trans gas ^) i ^^ from an inlet tube 852 connected to the blower housing qfX $$ f $ he

INDUSTRIAL blower assembly 70 and exits conveying gas through an outlet tube 854 connected to suction manifold 84. Each inlet tube 852 5 and outlet tube 854 is insulated and can be configured as separate Inner and Outer tubes using separate rings. Inlet tube 852 can be connected to blower housing 710 perpendicular to the direction of the transport gas flow to limit the admission of powder into detection chamber 850.

As shown in Figure 43, 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 layout block 50. Detection chamber 850 may include a 860 relative humidity detector, 862 temperature detector, and 864 pressure detector. In the embodiment of Figures 42 and 43, the relative humidity detector 860 Includes a temperature detector, which allows cross-checking against the temperature values ​​detected by the temperature detector 862. A discrepancy in the readings may indicate that the Detectors are caked with dust and therefore do not provide accurate detection. An air baffle 866 is mounted in a lower housing 858. The 850 detection chamber provides accurate detection of the transport gas conditions in the dust transport system.

In Figure 44, a representation, powder filling and assembly procedure for a cartridge is shown, which is inserted into the system in a cartridge tray and placed on the weight detection probe 112a to its filling. The bottom of cartridge 900 is filled with a drug powder by means of a powder supply module 54 such as that described in detail above. After filling, an upper part of cartridge 902 is press-fit onto the bottom of cartridge 900 to provide a complete cartridge 910 ready for sealed packaging.

As noted above, the powder delivery and detection apparatus of the present invention can be used to fill different types of containers. In another embodiment, the powder delivery and detection apparatus is used to fill a compact inhaler as described in US Patent No. 6,923,175 issued August 2,

2005 for Poole, et al. As illustrated in Figure 45, a bottom of the cartridge

920 The compact inhaler is placed on a weight detection probe 112a for filling. The bottom of the cartridge 920 is filled with a drug powder by means of a powder supply module 54 like the one described above. Then, an upper part of cartridge 922 is attached to the bottom of cartridge 920 and a nozzle housing 924 attached to the cartridge assembly. Finally, a powder cover 930 is press-fitted onto the mouthpiece housing 924 to provide a complete compact 932 inhaler ready for sealed packaging.

Having thus described various a¿pe ^ oj ^ -po | At least one embodiment of the present invention will be appreciated ^ &amp; ftá &amp; féíSaá

INDUSTRIAL alterations, modifications and improvements will easily occur to those skilled in the art. Such alterations, modifications and improvements are intended to be part of this description, and are intended to be within the spirit and scope of the present invention. Accordingly, the foregoing description and drawings are exemplary only.

NOVELTY OF THE IMPI INVENTION

MEXICAN INSTITUTE OE THE PROPERTY

INDUSTRIAL