MXPA01005742A

MXPA01005742A - Dry powder inhaler

Info

Publication number: MXPA01005742A
Application number: MXPA/A/2001/005742A
Authority: MX
Inventors: Michael Birsha Davies
Original assignee: Glaxo Group Limited
Priority date: 1998-12-11
Filing date: 2001-06-07
Publication date: 2002-03-05

Abstract

A metering device suitable for use in a dry powder inhaler comprises a housing defining a reservoir. The reservoir contains a powder. A rotatable auger, having a first and second end, has one or more flutes extending between the ends. The first end of the auger communicates with the reservoir. A dosing member, defining a dosing recess having a desired volume, is positionable adjacent said second end of said auger. Rotation of said auger causes the powder to be transferred through the flutes and into the dosing recess to fill the recess volume with a specific dose of powder.

Description

DRY POWDER INHALER FIELD OF THE INVENTION The present invention relates to a dry powder release device, and in particular to a dry powder release device having application in dry powder inhalers to deliver to a patient a metered dose of a formulated pharmaceutical substance in the form of dust.

Background of the Invention The release of therapeutic, prophylactic and diagnostic agents to a patient's lungs can be achieved using a variety of inhaler devices. A class of dry powder inhalers includes a reservoir based on dry powder systems. The deposit based on inhalers that contain a volume deposit of a bioactive agent (therapeutic, prophylactic or diagnostic) appropriate for inhalation, a mechanism for measuring the volume of powder in individual doses, and a mechanism to disperse the dry powder in a patient's inhalation path to release it into the lungs. The deposit based on dry powder inhalers must be operated within the restrictions given by the REF: 128609 use of dry powders in volume. For example, the powders used within normal dry powder inhalers do not flow perfectly and always have a degree of consistency. Thus, great care must be taken to ensure dust flows within the device to ensure that the powder reaches the appropriate point where it is measured. This is usually achieved by mixing the powder with an excipient, which is less cohesive and allows the powder to flow. The excipient also acts to dilute the active agent within the powder mixture allowing more accurate measurement of the potent active agents at an appropriate dose. Although the excipients have several beneficial effects as regards the flow and measurement of the powder, as a general rule, the release of non-critical material will be avoided. Therefore, where possible, the best practice is to reduce the amount of non-essential excipients in a mixture. The flow of powders within the inhaler devices can be effected by other mechanisms. For example, movement of the powder through a device to make it available for measurement in doses can be aided by applying a charge to the powder within the reservoir. The load can be applied with a plunger deflected by a spring that exerts pressure on the powder.

The movement deflects the powder charge towards the dosing mechanism in the device. This loading mechanism can, however, create a compression effect in the powder. The compressed powder can be "bonded" to or near the dosing mechanism and therefore no greater flow is desired. Therefore, it is desirable to avoid bonding the powder. An important consideration in a reservoir based on the dry powder inhaler is how the inhaler ensures accurate measurement of the bioactive agent in doses, and ensuring that this measurement can be repeated uniformly within firm tolerances. In a depot-based system, on the compaction of a therapeutic powder while measuring a given dose or multiple release dose of powder to a patient where a single dose is desired, it can be carried in an overdose. Depending on the agent to be measured, an overdose can cause serious side effects. Likewise, the release or not partial release of a dose of medication to a patient, may fail to provide the desired therapeutic effect, also carried for potentially life threatening situations, depending on the condition to be treated. Deposit based on dry powder inhalers are well known in the art. For example, WO 92/18188 and WO 93/03782 describe inhalers that include powder reservoirs containing a pharmaceutical substance, generally combined with a powdery volume agent. A rod or dosing shaft is moved within the reservoir to fill a cavity measured therein. The rod or shaft is then removed from the reservoir to release the measured dose to an inhalation channel, where the dose can then be inhaled by the patient. WO 92/04928 describes an alternative reservoir based on the inhaler system wherein the measuring mechanism is entrusted to an auger or auger positioned coaxially with the shaft of the reservoir. A plunger in the device deflects the powder towards the end of the auger. The endless screw pushes a "finger" of compressed powder to its opposite end which is then cut at the end of a full turn. This "finger" provides the measured dose. Although the reference states that the precise size dose will be released, it does not appear to prevent the endless screw from being rotated repeatedly so that the patient can inhale a plurality of doses in a single inhalation. Furthermore, the parallel and coaxial position of the worm inside the reservoir potentially causes loss, due to the fact that when the coaxially aligned piston ends at the end of the worm, there is no greater deviation of the powder towards the auger. The remaining powder is not available to be released to the patient, thus shortening the useful life of the device. In contrast to the devices of the prior art, the object of the present invention is to directly address the powder flow, the powder content, the accuracy of dose and reproducibility concerned required for the deposit based on dry powder systems. The present invention provides a new measurement system for dry powders having application in the area of dry powder inhalers. In particular, the present invention provides a measurement system for use in a manual dry powder reservoir based on inhalers. The measurement system can also be used in any case where reproducible and accurate measurement of the powders is desirable.

Brief Description of the Invention The present invention provides a dry powder measurement system usable in dry powder inhalers comprising a housing, having a wall portion defining a reservoir containing a powder. A hole pierces the tank at one end. A grooved auger positioned on the inner surface allows dust to move through the inner surface. The auger communicates with a perforated outlet, where the powder passes into a cavity in a dosing member positioned adjacent the perforated outlet. The cavity of the dosing member is of a desired volume and the dosing member is movable between a loading position adjacent the perforated outlet and a release position where the powder can be released. The orientation of the auger deposit within the inner surface is non-coaxial and non-parallel. Preferably, the axis of the reservoir is transverse to the axis of the bit, for example at about 90 degrees, with the reservoir opening only in a portion of the cylindrical surface area of the bit, for example 50% or less than 50% of the surface area. The auger and perforated outlet were designed so that turning the auger transfers the powder into the dosing cavity, but excessive rotation does not compress the powder into the dosing cavity. The release of the powder into the cavity can be made more reliable by increasing the volume of the perforated outlet to form an intermediate chamber. The intermediate chamber, which is described below in reference to the preferred embodiment, can act even to form cavities within the powder and can reduce the likelihood that the dead space will be created within the dosage cavity. Therefore, the present invention relates to a powder release device comprising a housing defining a reservoir, an inner surface and a perforated outlet, the reservoir has a surface and a bottom and an axis therebetween. The inner surface extends into the housing from a perforated outlet, and the inner surface and the reservoir are cut at an interface of the inner surface / reservoir. The inner surface has an axis, which is non-parallel and not coaxial with the axis of the reservoir. A rotatable auger is positioned coaxially inside the inner surface. The auger has a spiral groove that extends between the interface of the internal surface / tank and the perforated outlet. The delivery device may also have a dosage plate having a dosing cavity for measuring the powder transferred from the perforated outlet. The present invention also relates to a dry powder inhaler apparatus having an inhaler body with an air inlet, an air outlet, and an air flow path therebetween. The inhaler further comprises a wall portion defining a reservoir and an internal surface, the reservoir has first and second ends and an axis therebetween, the inner surface extending from a perforated outlet in the housing. The inner surface and the reservoir are in communication at one end of the reservoir at an interface of the inner surface / reservoir. The inner surface has an axis and the internal surface axis is non-parallel and not coaxial with the axis of the reservoir. A rotatable auger is positioned coaxially inside the inner surface. A spiral groove is defined in the auger and the groove extends between the interface of the inner surface / reservoir and the perforated outlet. The inhaler also has a dose plate that has been defined within a dosing cavity. The dose plate is movable between a loading position where the dosing cavity is in communication with the perforated outlet and a release position where the dosing cavity is in communication with the air flow path.

Additionally, the present invention relates to a method of releasing a powder to the respiratory tract of a patient comprising: a. providing a dry powder inhaler having an air inlet, an air outlet and a defined air flow path therebetween, the inhaler additionally comprising: (i) a housing defining a reservoir and an internal surface, the reservoir it has a surface, a bottom and an axis between them, the inner surface extends from a perforated outlet in the housing, the internal surface and the reservoir communicating in the bottom of the reservoir at an interface of the inner surface / reservoir, the internal surface has an axis, the axis of the internal surface is non-parallel and not coaxial with the axis of the deposit; (ii) a powder positioned inside the tank; (iii) a bit positioned within the inner surface, the bit is coaxially rotatable from within the inner surface, the bit has a spiral slot defined therein, the slot extends between the interface of the inner surface / deposit and the perforated outlet; (iv) a dose plate defining a dosing cavity, the dosing cavity positioned adjacent the perforated outlet, the dosing cavity exible in the air flow path; and b. turn the auger to transport the powder from the reservoir into the auger slot and into the dosing cavity. c. Expose the dosing cavity to the air flow path; d. Create an air flow in the air flow path; e e. Introduce the powder contents of the dosing cavity into the air flow to release the powder to the patient. Therefore, the present invention is based on the surprising realization that the binding of powders can be reduced or avoided in a release device having an auger that connects a reservoir in a non-parallel manner. Thus the orientation also allows to empty the dust deposit, therefore minimizes the loss of dust and maximizes the useful life of the device. The orientation of the auger and the reduction of potential binding sites can also produce a benefit allowing the exact release of less flowable powders, while potentially allowing the use of powder mixtures with the current excipient reduced for the drug proportions. Additionally, the present invention is based on the surprising realization that an auger can be used to feed the powder from a reservoir to a dosage cavity, with the amount of active agent measured remaining constant, regardless of the number of times the auger it is turned after the proper dose has been measured. It is desired that excessive spinning of the auger will force the powder from the deposit into the dosing cavity and thereby overcompact the powder at that point. Surprisingly, however, it has been found by the inventors that the powder slides by itself, and that the dosing cavity can reliably release a metered dose with only a predetermined minimum twist of the bit. The exact measurement is therefore not affected by the excessive turning of the auger. Additionally, the present invention is based on the surprising realization that the inclusion of an intermediate chamber in the perforated outlet is useful in equalizing the cavity and reducing the dead space in a dosing cavity, thereby producing a more accurate dosage of a powder measured These and other intentions and advantages will be evident in the description provided herein.

DESCRIPTION OF THE FIGURES A preferred embodiment of the invention is described in detail below, for example only, with reference to the following drawings in which: Figure 1 is a sectional view of one embodiment of a device for measuring powder according to the present invention. Figure 2 is a schematic view of the device of Figure 1. Figure 3 is a sectional view of a possible powdered medicament inhaler incorporating the delivery device of Figure 1, where the nozzle cover of the inhaler is closed and The dose plate is in the loading position. Figure 4A is a sectional surface view of the inhaler of Figure 3 with the mouthpiece partially exposed.

Figure 4B is a lower sectional view of the inhaler as shown in Figure 4A. Figure 5 is a lower sectional view of the inhaler of Figure 3 with the nozzle being fully exposed.

Description of the invention A device for releasing the powder in a dry powder inhaler is shown in Figures 1 and 2. The device 10 comprises a housing 12 defining a portion with wall 13 that forms a reservoir 14 for a pharmaceutical powder P. The reservoir 14 communicates with an internal surface, where an auger 16 having grooves 17 remains. The intersection of the reservoir with the internal surface is referred to herein as the "internal surface / reservoir interface". The reservoir 14 of the delivery device 10 contains a volume amount of powder P. The bit 16 acts, as described hereinafter, to feed the powder P to a dose plate 18 where a dosage cavity is formed. The reservoir 14 is elongated and extends transversely to the auger 16. The auger and the reservoir are oriented in a non-parallel manner and not coaxially with each other. Preferably, as shown in Figure 1, the tank and auger are oriented at an angle of approximately 90 degrees to each other. It is believed that the parallel, non-coaxial arrangement of the auger and the deposit leads to a more uniform dust collection. As the edge of the groove 17 is continuously moving along the interface of the inner surface / deposit, the probability that the bonding occurs at the interface of the inner surface / deposit is theoretically minimized, producing the increase of powder flow in the device. In the preferred embodiment, the reservoir 14 is circular in cross section and therefore is basically cylindrical in shape. The width of the reservoir adjacent to the bit is approximately equal to the diameter of the bit so that the reservoir opens about half the circumference of the bit. The adjustment to an equal size of the deposit and the diameters of the auger allows to empty the contents of the deposit during the use, therefore the amount of unusable dust in the deposit is minimized. At one end of the reservoir there is a reservoir lid 22 fixed to the housing 12 by means of a bolt 24. The annular cavities 26 inside the housing are for the seals 28 which are sealed against the internal cylindrical portion of the reservoir lid 22 to prevent the entry of moisture and the exit of dust. A float or reservoir piston 30 is located within the reservoir. The plunger is pushed out of the lid 22 by a spring of the reservoir 32. The powder is deflected towards the interface of the inner surface / reservoir, and towards the bit 16, by the pressure exerted by the plunger 30. The characteristics of the spring are they select to push the powder towards the interface but without causing the binding of the powder. In the described embodiment, the bit 16 is between 4 mm to 10 mm in diameter, and is preferably about 6 mm in diameter. The diameter of the auger, however, can be varied according to the requirements for which the device will be used. An auger cap 36 is connected to the auger 16, and the cover provides an appropriate drive mechanism, such as a gear 36a. The auger 16 is sealed inside the housing 12 by means of a rotary seal 38. At least one and preferably two helical grooves or splines 17 are located on opposite sides of the auger 16. In one embodiment, each groove is rotated by approximately 90 degrees over the length of the auger. At any time, the bottom of the tank 14 communicates with a grooved part 17 of the auger and with a non-grooved part a "flat part" 42. The number of grooves may vary, such as its size, shape and inclination, as well as the characteristics of its cutting edge or the proportion of the grooved area to the area of the flat part. The auger 16 is designed such that the powder in the perforated outlet 34 and in the dosing cavity 20 is not overly compacted., even after the repeated spin on the auger. Therefore, to provide a reliable measured dose of powder, it is only necessary to return the auger to a predetermined minimum number of turns (for example three) but the extra turns do not lead to an excessive dose nor to the compaction of the powder already in the dosage cavity. The release device is thus relatively safe, as it is relatively simple in construction. The optimum characteristics of the bit will thus be determined by the physical characteristics of the powder P released, that is, as its cohesiveness. The powders tend not to flow completely free, and the pharmaceutical substance may comprise only a small proportion of the total mixture. The cohesiveness of the powder in the mixture may be a function of the medicament, or the bulking agent or both. With highly cohesive powders, a different design may be required in place of the relatively free flowing powders, for example, an increased rib size may be desired. The auger design should be chosen such that efficient feeding of the powder from the reservoir to the dosing cavity is achieved, but over compaction of the powder in the dosing cavity does not occur in the repeated spinning of the auger. The powder, which flows in the grooves of the auger under the force of deflection of the piston, is transported on the spin of the auger in a threaded archimedia manner along the length of the auger and in the perforated outlet 34. The outlet perforated 34 is located at the terminal portion of the inner surface adjacent to and in communication with the dosing cavity 20 of the dose plate 18. In the preferred embodiment, the perforated outlet comprises a chamber between the grooves and the dosage cavity being referred to in the present as an intermediate camera. The shape of the intermediate chamber 34 in the preferred embodiment is frusto-conical. The intermediate chamber is generally circular in cross-section, to equalize the cross-section of the auger, but has an inclined surface to directly reach the profile of the rounded dosing cavity 20. The entrance of the chamber is therefore of the same diameter with relation to the diameter of the internal surface, while its outlet diameter is the same size in relation to the opening of the dosing cavity. It is desired that the intermediate chamber be useful for several purposes. It is believed that by reducing the cavity within the chamber and distributing the powder pressure in such a way that a uniform dosage is provided in the dosing cavity. The presence of the intermediate chamber also prevents the formation of dead space (ie, areas not actively filled by the powder leaving the perforated outlet) in the dosing cavity avoiding the risk of creating voids in the powder producing a low dosage of the measured medication. In such a case, it is assumed that the powder coming out of the grooves fills the intermediate chamber and the dosing cavity and that when the two are filled to capacity, the powder then slides into itself within the chamber between the grooves and the dosing cavity, by which the over compaction of the powder is avoided. As mentioned above, overcompaction can theoretically result in the release of more medication than desired to the dosing cavity, creating the potential for overdosing. As seen above, the dose plate 18 is approximately in the form of a quarter of a circle. The quarter circle has an angled corner and an arched hypotenuse through the angled corner. A rotating pin 44, on which the dose plate rotates, is positioned at the angled corner and extends perpendicularly from the dose plate. The dosing cavity 20 is positioned on the other side of the plate, in alignment with the perforated outlet. As shown in Figure 1 and 2, the housing 12 and the dose plate 18 are positioned in a reservoir receptacle 48. A dosage slit 46 is formed within the reservoir receptacle 46. The pin 44 fitted on the front of the dose plate 18 extends through the reservoir. another cavity in the reservoir receptacle 48. The receptacle 48 is closed on its front face by means of a front sliding plate 50. A rotary gear 52 is mounted around the rotary bolt 44, inside the reservoir receptacle 48. The spring of the The dose plate 54 (Fig. 2) is mounted within an opening in the reservoir receptacle 48 and is contracted between the faceplate 50 and the dose plate 18 to hold the plate 18 in a sealed orientation to the housing 12. As will be explained in detail below, about the rotation of the gear 52, the dose plate 18 is rotated pivotally, causing the dosing cavity 20 to move out of the perforated outlet 34 and through the a slit 46. The elongated shape of the dose plate allows the remaining surface of the dose plate to cover the outlet, preventing the leakage of the powder. The plate can also act to prevent the ingress of moisture if it is fitted with appropriate sealing mechanisms or if it is constructed of or coated with a material having the sealing characteristics. The delivery device described above can be used as a component in a dry powder medicament inhaler. This component can either be an integral part of the inhaler, or more appropriately, it can be formed as a cartridge that is inserted into an inhaler having a receiving spring, as depicted in Figures 3-5. Figures 3-5 show a preferred powder medicament inhaler of the present invention wherein a delivery device 10 has been inserted. In Figure 3, the inhaler device 100 comprises an exterior inhaler body 102 and an integrated nozzle cover 104. The outer inhaler body 102 defines a release device spring 106 into which the release device 10 has been inserted. The inhaler also defines an air flow path 108 extending between an air inlet 110 and an air outlet in the air. the shape of a nozzle 112. The integrated nozzle cap 104 is slidably rotatable within the outer inhaler body 102, on a center of rotation 103. When the lid is closed, as described in Figure 3, the integrated lid covers the nozzle 112. When the device is opened, the lid retracts into the outer body, exposing the nozzle 112. The integrated nozzle cover 104 has a butterfly handle 1 16 to assist in the opening and closing of the inhaler. The integrated nozzle cap also carries several internal components that are not visible from the outside of the inhaler. An arm 118 of the curved auger gear extends from the upper right side of the lid 104 and is positioned to engage the spur gear 36a of the release device 10. To facilitate the complementary engagement of the auger gear, the arm of the gear 118 has a toothed portion 120 corresponding to the serrations in the gear of the bit 36a. A transfer arm of the dose plate 122 extends from the lower right hand side of the integrated nozzle cover 104. The transfer arm 122 of the dose plate also has a toothed portion 124, which is adapted to engage the rotating gear of the dose plate 52 of the release device 10 after a certain degree of rotation of the integrated nozzle cover 104. Although not shown, the integrated nozzle cover 104 can also be coupled to a flow path closure of air that is positioned to block the air flow path 108 when the integrated nozzle cover 104 is closed. When the lid is opened, the closure moves out of the air flow path 108 to allow inhalation through the device.

Description of the Release Device in Use As mentioned above, the delivery device of the present invention was designed to be an internal component of a dry powder inhaler, or more preferably to be a separate cartridge, which can be inserted into an inhaler. Dry powder equipped with a cartridge spring designed to receive a device. In the cartridge version, a modality which is described in Figures 3-5, the release device 10 is inserted into the cartridge spring 106 in the portion of the outer inhaler body 102 of the inhaler 100. Already inserted, the device The release is located such that the gear of the drill bit 36a is aligned to engage by the toothed portion 120 of the drill gear arm 118, and the transfer arm of the dose plate 122 is aligned with the rotary gear of the dose plate. 52. As shown in Figure 3, to open the inhaler 100, a patient slides the butterfly handle 116 through the inhaler in a counterclockwise direction to expose the mouthpiece 112, as represented by the arrows . The integrated nozzle cap 104 rotates inside the inhaler body 102, and the toothed portion 120 of the drill gear arm 118 engages the spindle gear 36. The coupled arm causes the auger 16 (described in Figures 1 and 2) rotate within the inner surface of the releasing device 10, whereby the powder is transferred from the reservoir 14 into the dosing cavity 20 of the dose plate 18 by means of the groove 17. The integrated nozzle cap 104 is designed so that the toothed portion 120 of the gear arm of the bit 118 is of an appropriate length to allow the dosing cavity 20 to be completely filled but the rotation of the bit to cease some time after fill up The number of turns that the auger makes when the nozzle is retracted can be quickly controlled by varying the diameter of the auger gear 36a, or by adjusting the length of the number of the toothed portion 120 of the boom gear 118 or the number of the auger. indentations in it. Figure 4A shows the relative position of the nozzle cap after the auger gear arm has been decoupled from the auger gear. From the background view described in Figure 4B, it can be seen that additional movement of the nozzle causes the toothed portion 124 of the transfer arm 120 of the dose plate to engage the rotary gear 52 of the dose plate. In the coupling of the rotary gear of the dose plate, the dose plate 18 starts rotating pivotally. The pivotal rotation of the dose plate 18 moves the dosing cavity 20 out of its loading position adjacent to the perforated outlet. When this turn is completed, the dosing cavity 20 is in communication with the air flow path 108, and is said to be in its "release position" which is shown in Figure 5. Placed in the position shown in FIG. Figure 5, the inhaler device 100 is held against the patient's lips and the patient inhales through the nozzle 112. Ideally, the inhaler will be held level by the patient so that the risk of spilling powder from the device is minimized . The inhalation causes a flow of air to be created in the air flow path 108, the contents of the dosing cavity 20 entering therein, and releasing a measured dose of the powder P to the lungs of the patient. To return the inhaler to the closed position, the butterfly handle 116 slides in a clockwise direction, causing the integrated nozzle cover 104 to return to its original position where nozzle 113 is covered. return to dose plate 18 to the loading position. The inhaler is then ready for a subsequent activation.

Convenient Powders in the Device The powder P contained within the reservoir can be any material that is desired to be measured. In the application envisaged for this release device, the powder is a medicament to be released to a patient by means of an inhaler device. Appropriate drugs for release by the inhaled route can therefore be selected from, for example: analgesics, such as, for example, codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations, for example, diltiazem; antiallergics for example, cromoglycate, ketoifen or nedocromil; anti-infectives, for example, cephalosporins, penicillins, streptomycin, sulfonamides, tetracyclines and pentamidine; antihistamines, for example, metapyrylene; anti-inflammatories, for example, beclomethasone dipropionate, fluticasone propionate, flunisolilda, budesonide, rofleponide, mometasone furoate or triamcinolone acetonide; antitussives, for example, noscapine; bronchodilators, eg, albuterol, salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetarin, tulobuterol, orciprenaline, or (-) - 4-amino-3, 5-dichloro- - [[[6- [2- (2-pyridinyl) ethoxy] exyl] ethyl] benzenemethanol; diuretics, for example, amiloride; anticholinergics, for example, ipratropium, tiotroprio, atropine or oxitropium; hormones, for example, cortisone, hydrocortisone or prednisolone; xanthines, for example, aminophylline, choline theophyllinate, lysine theophyllinate or theophylline; therapeutic proteins and peptides, for example, insulin or glucagon; vaccines; diagnostics; and gene therapy agents. It will be clear to one skilled in the art that, where appropriate, the medicaments can be used in the form of salts, (for example, as the alkali metal or amine salts or as acid addition salts) or as esters (for example, low alkyl esters) or solvates (eg, hydrates) to optimize the stability and / or activity of the medicament. Preferred medicaments are selected from albuterol, salmeterol, fluticasone propionate and beclomethasone dipropionate and salts or solvates thereof, for example, albuterol sulfate and salmeterol xinafoate. The drugs can also be released in combinations. Preferred formulations containing combinations of active ingredients containing salbutamol (for example, as the sulfate or free base salt) or salmeterol (for example, as the xinafoate salt) in combination with an anti-inflammatory steroid such as an ester of beclomethasone (for example, dipropionate) or a fluticasone ester (for example, propionate). In fact, it is envisaged in accordance with this invention that any prophylactic or therapeutic agent, of appropriate diagnosis, can be included as the powder P within reservoir 14 of the present apparatus. Generally, medicament particles suitable for delivery to the bronchial or alveolar region of the lung have an aerodynamic diameter of less than 10 microns. Another size of the particles can be used if the release to other portions of the respiratory tract is desired, such as the nasal cavity, mouth or throat. The medicament may be a pure drug, but more appropriately, it is preferred that the powder P comprises a drug mixed with a bulking agent (excipient), for example, lactose. Additional powders can be made with densities, size ranges, or particular characteristics. The particles may comprise the active agents, surfactants, wall-forming materials, or other components considered desirable by the experts.

Usually mixtures of bulking agents and drugs are formulated to allow accurate measurement and dispersion of the powder in the doses. For example, a normal mixture contains 13,000 micrograms of lactose mixed with 50 micrograms of drug, producing an excipient for a drug ratio of 260: 1. Because the present invention can measure and distribute the mixtures more precisely and efficiently, the dosage blends with the excipient can be used for the 60: 1, and potentially 2: 1, drug ratios. At very low mixing levels, however, the reproducibility of the drug dose becomes more variable.

Experimental Data Example 1 A measuring apparatus developed as described above has 6 mm diameter auger and a dosing cavity of sufficient volume to hold 3 mg of powder. The device was filled with a mixture of micronized lactose and fluticasone propionate (FP) in a ratio of 60: 1 (3000 parts of lactose to 50 parts of FP). The test was conducted by rotating the auger in a certain number of turns and then determining the amount of active agent in the dosing cavity. Each indicated turn was repeated approximately 10 times and the results for each time taken. The average amount of active material for each group of turns was taken, and the RSD calculated. The test was considered successful because of dose uniformity if RSD was less than 10% for each group. The results shown in the following table indicate an acceptable uniformity for a 60: 1 mix Alternative Modes The description of the device provided above only describes the preferred embodiment of the device. It is considered that alternative embodiments are within the scope of the present invention, as will be appreciated by those skilled in the art. For example, the deposit 14 could be of any shape or size. The deposit could be circular or poly-angular in cross section. In relation to the size of the internal surface, the deposit diameter could be larger or smaller than the internal surface. Where it is larger than the diameter of the inner surface / auger, the base of the deposit could taper to join with the auger. As mentioned above, the auger / inner surface may be in any orientation that is non-parallel and not coaxial with the axis of the deposit. Although a tangential or perpendicular arrangement is preferred, the auger / inner surface may be oriented towards or away from the end of the inner surface. In the case where the shape of the reservoir or auger angle of the orientation reservoir is different, the piston 30 will be ideally adjusted to conform to the modified characteristics. For example, in the case where the diameter of the deposit was octagonal in cross section, it was larger than the diameter of the inner surface, had a tapered base leading to the interface of the inner surface, and had an axis that cuts the 'axis of the inner surface / auger at 45 degrees (the auger is inclined towards the dose plate cavity), the plunger will also be octagonal in cross section to be in contact with the sides of the deposit, it will also be tapered in correspondence to the sharpening of the base of the tank, and will be oriented at 45 degrees to conform and align with the angle of the auger axis / internal surface. The piston 30 in the preferred embodiment is deflected against the powder by means of the spring 32. Alternatively, the piston can be deflected by mechanisms such as the spring. Any pressure created by the means can be incorporated, for example a pressurized piston can be used. The feeding mechanism configured to load the dosing cavity is functional in any orientation, and is not of dependent severity. In addition, it does not require shaking or any other agitation. The intermediate chamber used can be of any shape, size or volume that allows a desired operation. The inclination of the walls may be altered and may be made larger or smaller than that described in the preferred embodiment. The side of the intermediate chamber may also be parallel, or tapered in a reverse manner to that shown in the preferred embodiment. Although the preferred perforated outlet comprises an intermediate chamber, it does not necessarily have to be this way. The grooves of the auger can be opened directly in the dosing cavity. The location of the perforated outlet can also be modified. It is considered to be within the scope of the present invention that the perforated outlet could be located at any point along the length of the inner surface where the powder will be fed by the auger. If an intermediate chamber is positioned along the length of the inner surface, opposite the end of the inner surface as in the preferred embodiment, the walls of the chamber will be oriented to conform to the curve of the inner surface. The outlet to the cavity may then be flat in profile, which is believed to be the best configuration to allow the dose plate to move in the air flow path when incorporated in an inhalation device. In the preferred embodiment previously described, the movement of the dosing member or dose plate is described as pivotally pivotal. It will be appreciated that a variety of movements could also be incorporated. For example, an alternative plate could slide longitudinally in the path of the air flow. It can also be provided that the plate can be modified to eliminate the need to move the plate at all. For example, a closure could be provided between the perforated outlet and the dose cavity to close the cavity after it has filled, and a port on the opposite side of the cavity from the perforated outlet could be incorporated in the dose plate, which it could be opened to expose the measured dose to the path of the air flow. It is also considered within the scope of the invention that the release device may be used as a removable cartridge unit that is fixed within a spring of any number of devices or as an integral non-removable part of the inhaler, with the housing of the device release formed by a wall portion of the inhaler. Additionally, the device can be used for delivery of drugs through the mouth or nose, and therefore the mouthpiece can now comprise a nasal actuator. The application of which this description and claims are a part may be used as a basis for priority with respect to any subsequent request. The claims of the subsequent application may be directed to any feature or combination of features described herein. They may take the form of the product, the composition, process or use requires and may include, by way of example and without limitation, one or more of the following claims.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers.

Claims

Having described the invention as above, the content of the following claims is claimed as property: 1. A measuring device suitable for use in a dry powder inhaler characterized in that it comprises: a. a housing defining a reservoir, suitable for containing a powder; b. a rotating auger that defines one or more grooves; the auger has first and second ends and where the groove extends between them, the first end is in communication with the deposit, and; c. a dosing member defining a dosing cavity having a desired volume, the dosing cavity is positioned adjacent the second end of the bit; whereby the spin of the auger causes the powder to be transferred through the grooves and into the dosing cavity to fill the volume, such that the direction of the powder transfer is not coaxial with the spin plane of the auger.
2. A powder release device characterized in that it comprises: a. a housing defining a reservoir, an inner surface and a perforated outlet, the reservoir has a first and a second end and an axis therebetween, the inner surface extends into the housing, and the inner surface and reservoir are in communication at the second end of the reservoir in a connection of the reservoir / internal surface, the internal surface has an axis, which is not parallel and not coaxial with the reservoir axis, the perforated outlet is in communication with the internal surface; and b. a rotating auger is placed coaxially inside the internal surface, the auger has a groove, which allows communication between the connection of the tank / internal surface and the perforated outlet, the direction of the dust transfer is not coaxial with the turning plane of the auger.
3. The device according to claim 2, characterized in that the axis of the tank is approximately perpendicular to the axis of the internal surface.
4. The device according to claim 2, characterized in that additionally comprises a dose plate defining a dosing cavity, the dosing cavity is in communication with the perforated outlet.
5. The device according to claim 2, characterized in that the perforated outlet comprises an intermediate chamber.
6. The device according to claim 5, characterized in that the intermediate chamber is sharpened towards the dosing cavity.
7. The device according to claim 4, characterized in that the dose plate is movable between a loading position where the dosing cavity is adjacent to the perforated outlet, and a release position where the contents of the cavity can be removed .
8. The device according to claim 7, characterized in that the dose plate is rotatably movable between the loading and release positions.
9. The device according to claim 1 or claim 2, characterized in that the bit has a circumference and the reservoir is connected with only a portion of the circumference of the bit at the interface of the reservoir / internal surface.
10. The device according to claim 1 or claim 2, characterized in that it additionally comprises a plunger positioned inside the tank and diverted towards the auger.
11. The device according to claim 1 or claim 2, characterized in that the inner surface extends through the housing, and the auger has an actuator at one end that facilitates the turning of the auger.
12. The device according to claim 2, characterized in that it additionally comprises a powder inside the tank.
13. The device according to claim 1 or claim 2, characterized in that the powder is selected from the group consisting of therapeutic, prophylactic and diagnostic agents.
14. The device according to claim 13, characterized in that the powder is selected from the group consisting of analgesics, anginal preparations, antiallergics, antiinfectives, antihistamines, antiinflammatories, antitussives, bronchodilators, diuretics, anticholinergics, hormones, xanthines, therapeutic proteins and peptides. , vaccines, and gene therapy agents.
15. The device according to claim 14, characterized in that the powder is selected from the group consisting of: codeine, dihydromorphine, ergotamine, fentanyl, morphine, cephalosporins, penicillins, streptomycin, sulfonamides, tetracyclines, pentamidine, diltiazem, cromoglycate, ketoifen, nedocromil, metapirilene, beclomethasone dipropionate, fluticasone propionate, flunisolildo, budesonide, rofleponide, mometasone furoate, triamcinolone acetonide, noscapine, albuterol, salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetarin, tulobuterol, orciprenaline, (-) -4-amino-3, 5-dichloro- - [[[6- [2- (9-pyridinyl) ethoxy] -ery]] methyl] benzenemethanol, amiloride, ipratropium , tiotroprio, atropine, oxitropium, cortisone, hydrocortisone, insulin, glucagon, prednisolone, aminophylline, choline theophyllinate, lysine theophyllinate and theophylline.
16. A dry powder inhaler apparatus having an inhaler body with an air inlet, an air outlet, and an air flow path therebetween, and characterized in that it additionally comprises: a. a wall portion defining a reservoir and an internal surface, the reservoir has a first end and a second end and an axis therebetween, the inner surface extends from a perforated outlet in the housing, and the internal surface and the reservoir they are in communication to one end of the reservoir at an interface of the inner surface / reservoir, the inner surface has an axis, which is not parallel and is not coaxial with the reservoir axis; b. a rotating auger coaxially positioned within the inner surface, a spiral groove defined in the auger, the groove extends between the interface of the inner surface / reservoir and the perforated outlet; the direction of the dust transfer is not coaxial with the spin plane of the auger; and c. a dose plate, the dose plate defines a dosing cavity, the dose plate is movable between a loading position, wherein the dosing cavity is in communication with the perforated outlet, and a release position where the cavity Dosing is in communication with the air flow path.
17. The dry powder inhaler apparatus according to claim 16, characterized in that it additionally comprises a loading arm capable of coupling the auger to cause the rotation thereof.
18. The dry powder inhaler apparatus according to claim 16 or 17, characterized in that it additionally comprises a transfer arm of the dose plate capable of coupling the dose plate to move it between the loading and release positions.
19. The dry powder inhaler apparatus according to claim 16, characterized in that it additionally comprises: a. an integrated nozzle cap positioned within the body of the inhaler, the integrated nozzle cap has a loading arm and a dose plate transfer arm, and wherein the integrated nozzle cap is movable between a closed position, wherein the dose plate is in the loading position, and an open position, where the dose plate is in the release position and the dosage cavity is in the air flow path.
20. The inhaler according to claim 16, characterized in that the perforated outlet comprises an intermediate chamber.
21. A method of releasing a powder to the respiratory tract of a patient characterized in that it comprises: a. provide a dry powder inhaler that has an air inlet, an air outlet and a defined air flow path between them, the inhaler additionally comprises: i. a housing defining a reservoir and an inner surface, the reservoir has first and second ends and an axis therebetween, the inner surface extends from a perforated outlet in the housing, the inner surface and the reservoir are in communication in the second end of the reservoir at an interface of the inner surface / reservoir, the inner surface has an axis, which is not parallel and is not coaxial with the reservoir axis; ii. a powder positioned inside the tank; 10 iii. a bit positioned within the inner surface, the bit is coaxially rotatable within the inner surface, the bit has a spiral slot defined in the 15 itself, the slot extends between the interface of the inner surface / reservoir and the perforated outlet; iv. a dose plate, which defines a 20 dosage cavity, the dosing cavity is positioned adjacent the perforated outlet, and the dosing cavity is exposed to the airflow path; and b. rotating the auger to transport the powder from the reservoir into the slot of the auger and into the dosing cavity, such that the direction of the powder transfer is not coaxial with the spin plane of the auger; c. Expose the dosing cavity to the path of the air flow; d. Create an air flow in the air flow path; and e. Introduce the powder contents of the dosing cavity into the air flow to release the powder to the patient.
22. A method for measuring powders characterized in that it comprises: a. providing a measuring device comprising: (i) a housing having a reservoir, which contains a powder; (ii) a rotating auger that defines one or more grooves; the auger has first and second ends and the groove extends between them, are one or more grooves in communication with the tank and; (ii) n dosage member defining a dosage cavity having a desired volume, the dosage cavity is positioned adjacent the second end of the bit; b. rotating the auger to cause the powder to move through the grooves of the reservoir to the dosing cavity, such that the direction of the powder transfer is not coaxial with the spin plane of the auger; c. enter the powder from the dosing cavity. DRY POWDER INHALER SUMMARY OF THE INVENTION A measuring device suitable for use in a dry powder inhaler comprising a housing defining a reservoir. The deposit contains a powder. A rotating auger, having first and second ends, has one or more grooves extending between the ends. The first end of the auger communicates with the deposit. A dosing member, defining a dosing cavity having a desired volume, is positioned adjacent the second end of the bit. The spin of the auger causes the powder to be transferred through the flutes and into the dosing cavity to fill the volume of the cavity with a specific dose of powder.