HK1078809A1 - Humidity-tight cartridge for a powder inhaler - Google Patents

Abstract

Pharmaceutical powder cartridge for powder inhalers for holding a pharmaceutical depot for several pharmaceutical powder doses has an integrated metering device comprising at least one metering slide which can be moved approximately transversely in a metering slide channel. The metering slide channel with the metering slide is sealed off from the environment at least on a filling position of the metering slide. Pharmaceutical powder cartridge (1) for powder inhalers for holding a pharmaceutical depot for several pharmaceutical powder doses comprises at least one storage space (6) and an integrated metering device comprising at least one metering slide (9, 13, 14) which can be moved approximately transversely in a metering slide channel (12) at least from a filling position to an emptying position approximately transversely with respect to the direction of flow of the pharmaceutical powder out from the storage space. The metering slide channel with the metering slide is sealed off from the environment at least on the filling position of the metering slide. An independent claim is also included for an inhaler for powdered pharmaceuticals, which comprises a pharmaceutical powder cartridge, and a holder for the pharmaceutical powder cartridge, where the pharmaceutical can be taken by a patient by way of an air stream.

Description

Moisture resistant cartridge for powder inhaler

Technical Field

The present invention relates to a pharmaceutical powder cartridge for a powder inhaler and a correspondingly mounted inhaler, the pharmaceutical powder cartridge being intended for filling a drug depot with a large dose of drug powder and having at least one reservoir and an integrated metering device, said integrated metering device comprising at least one metering slide which is movable approximately transversely in a metering slide slot, at least from a loading position to an emptying position, which is approximately transverse to the direction of flow of drug powder from the at least one reservoir.

Background

In the field of the treatment of bronchial diseases, but also other diseases which can be administered via the respiratory tract, it is known not only to atomize solutions or suspensions into inhalable aerosols, but also to use pulverulent medicaments. Many examples of these drugs are described in the literature and WO93/11773, EP 0416950A 1 and EP 0416951A 1 are cited merely for illustration.

In this regard, a common form of administration is the delivery of drugs by inhalation devices (inhalers).

Known inhalers that can be used for powdered medicaments include those for single dose administration and also inhalation devices having a reservoir that can be used for large doses of medicament. In relation to the latter, it is known to provide separate reservoirs for each single dose, as well as to receive multiple doses of medicament with a single containment space.

Known inhalers providing a large number of single doses of medicament in separate reservoirs include those wherein the individual spaces are each filled with a dose of medicament. An example of such an inhaler is described in US5,301,666 a. In addition, it is also known to contain a large dose of medicament powder in a separate space, referred to as a blister container. An example of such a blister container for use with an inhaler is described in DE 4400083C 2. Such a blister container is described, for example, in DE 4400084 a1, and at the same time it is also designed as a disposable inhaler.

For example, in the inhalation device described in DE 19523516C 1 blister containers can be inserted, which each have a separate reservoir for a single dose of powdered medicament and which can be emptied one after the other by means of the inhalation device.

Many examples of inhalers having reservoirs that can be used for large doses of medicament are described in the prior art. An example with a replaceable storage container is described in german patent specification 846770, another such example being described in WO 95/31237.

A significant challenge in inhalation systems where a common reservoir contains a large dose of a pharmaceutically active substance is the apportionment of a single dose to a single inhalation. In this regard, many solutions have been proposed, such as those described in US 2,587,215a and US4,274,403A. In addition, other types of devices for metering individual doses of medicament powder from reservoirs containing large doses of medicament are described in WO 92/09322, WO 93/16748, DE 3535561C 2 and GB 2165159 a. DE 19522415 a1 describes a replaceable cartridge containing a large dose of medicament powder with an integrated metering slide.

Another important problem with inhalation of pharmaceutical powders is the disintegration of botanical powder formulations into particles that can enter the lungs. The active substances to be administered in this way are usually used in combination with excipients in order to achieve a reasonable administration dose of the pharmaceutically active substance and also to further modify the properties of the pharmaceutical powder, for example to influence its shelf life.

For example, the proposed solutions for powder inhalers, by means of which particles that can enter the lungs are obtained in the inhaled air stream, are described in EP 0640354 a2, US5,505,196A, US5,320,714 a, US5,435,301A, US5,301,666A, DE 19522416A 1 and WO 97/00703. Methods of generating a gas stream using secondary energy are also known, for example as described in ZA-a 916741.

In the case of medicaments in powder form for inhalation, it is known to use active substances in combination by applying a prepared active substance mixture. Corresponding processes, such as the combined use of salmeterol and fluticasone, or formoterol and budesonide, are also proposed in EP 0416951A 1 and WO 93/11773.

The documents published in WO 00/74754 and 20 for many years have demonstrated that there are considerable difficulties in addressing moisture, particularly in powder inhalers. Moisture can not only have an adverse effect on the pharmaceutically active ingredients of the medicament, but in particular it can also impair the interaction of the physical and chemical parameters of the combination of active substance and auxiliary agent. As a result, for example, lumps may form or the disintegration of the inhaled powder into particles that can enter the lungs may be affected. All of these conditions can create difficulties that affect the metering and therapeutic effectiveness of the powdered medicament.

In order to minimize these disadvantages, various attempts have been made in the past to reduce the penetration of moisture into the powder inhaler by using a sealing strip. Attempts have also been made to reduce the adverse effects of moisture that has penetrated, particularly by keeping the air moisture in the storage chamber to a minimum, by absorbing the moisture using a desiccant.

Prior Art

In the prior art, WO 00/74754 explicitly describes that this problem is usually only solved by using various forms of desiccants. The applicant claimed for the first time that this problem is solved by using a sealing strip that prevents the penetration of moisture into the inhaler, in particular into the storage container of the powder inhaler by using a particularly elastic closing member.

For this purpose, it is mentioned that the closure parts are composed of "various known and customary materials, such as natural or synthetic rubbers, silicones or PTFE" and similar materials.

Subsequently, reference is made to the Innovata Biomed "Clickhaler" powder inhaler, which describes in detail an apparatus which is a special device in the metering configuration of this inhaler and which comprises a metering device in the form of a star feeder in the form of a truncated cone.

In the description of the embodiments, the closure member is provided as a closure sleeve resembling a truncated cone, which is fixed to the truncated metering cone and is required to be pivotable so that it can assume a closed position and an unclosed position. Page 5 here, it is interesting to describe how this closure sleeve is preferably made of a synthetic material like a metering cone. It is further proposed that the number of bores of this closure sleeve is the same as the number of metering chambers of the metering cone part. The closure sleeve and the metering member are designed in the following manner: when both are rotated, the metering chamber formed by the opening in the closure sleeve first extracts the drug from the reservoir, then, once rotated again, deposits this drug again in the metering chamber of the actual metering cone, and finally transfers them from there into the air passage.

In a particularly advantageous embodiment, the outer curved surface of the closure sleeve forms a spherical cross-section, which conforms well to the corresponding curvature of the drug reservoir. The inner curved surface of the closure sleeve is required to conform to the frustum of the metering cone.

From US 6,132,394a it is known to provide a separate container containing a desiccant in the chamber of the inhaler. This is in contrast to that described in US4,274,403a, where separate containers are used which are completely closed, which are constructed of a material which is as moisture-permeable as possible, and in which a desiccant, for example silica gel, is placed. This has the major advantage that no fitting or connection points allow a small amount of desiccant to enter the drug cavity and contaminate the powdered drug, as compared to conventional dry containers. In conventional drying vessels, these connection points are present in particular between the vessel body and the porous membrane, through which moisture can enter the drying agent.

Therefore, it is required that such a separate container is composed of a single material as much as possible, preferably a material having high moisture permeability. Suitable materials proposed are Polycarbonate (PC) and ABS (acrylonitrile-butadiene-styrene). It is desirable here to modify the drying action over a relatively long period of time by means of such a material of the container.

WO 01/46038 discloses the use of plugs, foils, sheets or liners of EVA copolymers containing 35-80% by weight of a desiccant such as silica gel, clay or zinc chloride, which can be used as desiccant capsules or enclosed in storage containers for packaging food products; mention is made of insufficient mechanical stability of such stoppers and the like; and discloses that there is a risk of mechanical breakdown when the desiccant concentration is relatively high. Here, the suitable EVA types contain a high proportion of vinyl acetate copolymers, and therefore these materials have a high moisture permeability.

WO 01/21238 discloses a powder inhaler with a sealed seal when not in use. To this end, in the case of a powder inhaler having a drug reservoir and an airway extending through the underside of the reservoir, a sealing strip is provided on each side of the reservoir and covers the air inlet and the inhalation port of the airway in the rest state. When the priming cap starts to push the metering piston through the storage space, delivering a dose of medicament from the reservoir into the air passage, the two sealing strips fixed to the priming cap are also pushed downwards until the metering piston reaches its emptying position. The sealing tape has through holes and they are arranged in the following way: when the actuating caps are in the end position, they leave the opening of the airway free. Air can be drawn into the airway as long as the primer cap is depressed. When the actuating cap is released and returns to its starting position, the air passage opening will close again.

By means of additional guiding means and the elastic design of the sealing band, these are pressed against the outer wall to increase the sealing action. In this arrangement, the sealing band progressively presses more strongly against the outer wall of the inhaler, with increasing distance of travel from the open position to the closed position, in a direction transverse to the direction of travel thereof. An elastic seal in the form of a bellows is also provided between the activation cap and the inhaler housing to close the gap between the structural parts.

Summary of the invention

It is therefore an object of the present invention to improve the delivery systems of known powdered drugs.

According to the invention, this object is achieved by a pharmaceutical powder cartridge for a powder inhaler for a drug depot for loading a large dose of drug powder, having at least one reservoir and an integrated metering device comprising at least one metering slide which is movable in an approximately transverse direction in a metering slide slot, at least from a full-loading position to an emptying position, in an approximately transverse direction with respect to the direction of flow of drug powder out of the at least one reservoir, at least in the full-loading position of the metering slide, the metering slide slot with the at least one metering slide being sealed off from the environment.

With the design of the present invention, the drug reservoir is protected from environmental moisture at minimal additional cost, especially during intermediate storage periods after initial use of the reservoir by the patient. This advantage is exerted both when the cartridge is mounted in the inhaler and when it is stored outside the inhaler. Compatibility with known powder inhalers of the kind mentioned at the outset with replaceable medicinal powder cartridges can be maintained.

In a particularly preferred embodiment, the pharmaceutical powder cartridge according to the invention is characterized in that the metering slide slot has an opening at one end which is open to the environment, through which opening part of the metering slide can pass, and around which opening the contact surface of the sealing strip is provided.

A particularly reliable function is obtained if the metering slide has a sealing surface in a plane approximately transverse to its direction of movement from the full position to the emptying position. In this way it is possible to avoid at the same time a change in the friction force during movement of the metering slide, which change may be caused by movement of the sealing strip along the sealing surface, powder residues or wear of the sealing strip in the known inhaler.

A particularly reliable seal can be obtained if the seal is provided by an elastic sealing strip.

In the case of extended storage of the pharmaceutical powder cartridge prior to insertion into the inhaler, it is ensured that a particularly durable and effective seal is obtained if the metering slide can be moved further into an additional storage position and at least the metering slide is elastically prestressed against the sealing strip in this storage position, in particular if this metering slide is held in this storage position by resilient means.

In a preferred embodiment, the pharmaceutical powder cartridge according to the invention is characterized in that the metering device comprises at least one metering chamber for carrying a predetermined amount of powdered medicament.

It is also advantageous if, for the administration of the active substance combination, the pharmaceutical powder cartridge has at least two reservoirs, in particular if the pharmaceutical powder cartridge has a metering device which has, for each reservoir, a metering chamber for dispensing a predetermined quantity of each pharmaceutical active substance provided in the reservoir. Depending on the provided active substance combination, it is also advantageous if the metering devices of the individual pharmaceutical powder cartridges have metering chambers of the same or different volumes.

If the pharmaceutical powder cartridge also has means for indicating the dose of medicament retained in or expelled from the reservoir, it may be a particularly economical application, particularly for expensive medicament powders which are only applied infrequently.

The advantages of the invention are particularly applicable to the long-term use of pharmaceutical powder cartridges for powder inhalers for drug depots loaded with large doses of drug powder, with at least one reservoir and an integrated metering device which can assume at least a full-load position and an empty position and which can be moved from the full-load position to the empty position, and with a sealing strip which can seal off the reservoir from the environment and prevent the ingress of moisture at least in the full-load position of the metering device, the sealing strip being elastically deformable during the movement of the metering device from its empty position to the full-load position, without the sealing strip sliding against a sealing surface.

In a preferred embodiment of the invention, the sealing strip is composed of a silicone rubber or elastomer, more preferably a thermoplastic elastomer, particularly preferably TPEE (thermoplastic polyester elastomer).

In addition, the improvement of the application properties of the invention is obtained by means of a pharmaceutical powder cartridge for powder inhalers, in particular by actively reducing the influence of moisture on the drug powder during use in a patient or medical facility, having at least one reservoir for a drug depot loaded with a large dose of drug powder, comprising a housing and a lid which substantially enclose the at least one reservoir, where the housing and/or the lid consist essentially of PVDC (polyvinylidene chloride), a fully or partially coated drug compatible plastic of PVDC, a heterocyclic side group containing olefin copolymer (COC or mPP) or PCTFE (polychlorotrifluoroethylene).

In a particularly advantageous embodiment, the pharmaceutical powder cartridge according to the invention is characterized in that the at least one metering slide as a component of the metering device is composed predominantly of PVDC (polyvinylidene chloride), PVDC-fully or partially coated, pharmaceutically compatible plastics, olefin copolymers containing heterocyclic side groups, at least partially oriented PP (polypropylene) or PCTFE (polychlorotrifluoroethylene).

In order to limit the effect of moisture penetrating into or present in the cartridge on the medicament powder, it is also useful if the medicinal powder cartridge for a powder inhaler of the invention is characterized in that the side of the housing and/or the lid facing at least partly the reservoir comprises a desiccant mixture embedded in a thermoplastic matrix.

In order to avoid damage to the drug by desiccant residues, it is advantageous according to the invention to provide a pharmaceutical powder cartridge for a powder inhaler with at least one reservoir, which can be used for powder storage of drug loaded large doses, which contains at least one shaped housing consisting of a mixture of thermoplastic matrices embedded in a desiccant, preferably silica gel, bentonite or molecular sieves. It is particularly advantageous if the channels are formed in a thermoplastic matrix of low water absorption, which channels can be formed by dissolving the soluble co-extruded components. It is also useful if the moisture-absorbing fibers are embedded as a filler in a low water-absorbing thermoplastic matrix in order to quickly absorb residual moisture in the reservoir.

For economical mass production it is particularly advantageous if the mixture of the low water-absorbing thermoplastic matrix and the drying agent embedded therein is designed as at least part of the inner wall of the reservoir, which can be done by multi-component injection molding in a housing consisting of a substantially water-vapor impermeable plastic.

It is also advantageous within the scope of the invention if the housing and the cover are sealed against water, preferably by ultrasonic welding.

For particularly economical production, the sealing strip is co-injected on the housing or the metering slide.

The present invention can be advantageously developed in economical aspects by applying the powder medicine inhaler with a medicinal powder cartridge of the present invention and an inhaler for powder medicine in which a patient can take the medicine therein by an air flow, characterized in that it is a container usable for the medicinal powder cartridge of the present invention.

The advantages of the present invention are particularly beneficial for patients in need of treatment with a pharmaceutical powder cartridge of the present invention containing a powder of one or more of the following active substances: analgesics, antiallergic agents, antibiotics, anticholinergics, antihistamines, anti-inflammatory agents, antipyretics, adrenocortical hormones, steroids, antitussives, bronchodilators, diuretics, enzymes, drugs acting on the cardiovascular system, hormones, proteins and peptides.

Application of the invention

With the present invention, even when they are sensitive to moisture or in adverse climatic environments, the pharmaceutically active substances in the form of powder drugs can be used for a long period of time; also in this case, there may be an advantage of a reusable inhaler in which the medicinal powder cartridge can be replaced.

Powdered medicaments for inhalation in different combinations of active substances under improved storage conditions are also made available, wherein the sensitivity of the individual active substances to moisture, which can influence the shelf life, stability or dose availability (dosability) of these substances, has been increased. The active substances which can be used according to the invention can also be, for example, beta-sympathomimetics: salbutamol, reproterol, fenoterol, formoterol, salmeterol. Possible examples of corticosteroids are: budesonide, beclomethasone, fluticasone, triamcinolone, loteprednol, mometasone, flunisolide, ciclesonide. Possible examples of anticholinergic agents are: ipratropium bromide, thiotropium bromide, glycopyrrolate bromide.

Possible examples of analgesics and antimigraine drugs are: morphine, tramadol, flupirtine, sumatriptan. Peptides and proteins that can be used are for example: cetrorelix, insulin, calcitonin, parathyroid hormone, coagulation factor VIII analogs, interferon alpha, interferon beta, heparin, FSH (follicle stimulating hormone), colistin, tobramycin.

The use is not restricted to the active substances mentioned here. The pharmaceutical powder cartridges are suitable for all active substances which, in powder form, can be metered and administered by inhalation. The invention is also applicable to compositions of active substances containing liquid ingredients, such as solutions or suspensions of pharmaceutically active substances, with suitable modifications of the system and the metering device.

Pharmaceutical powder formulations which can be used with the pharmaceutical powder cartridge system of the present invention may contain various active substances, for example, analgesics, antiallergic agents, antibiotics, anticholinergics, antihistamines, antiinflammatory agents, antipyretics, adrenocortical hormones, steroids, antitussives, bronchodilators, diuretics, enzymes, cardiovascular drugs, hormones, proteins and peptides. Examples of analgesics are codeine, diamorphine, dihydromorphine, ergotamine, fentanyl and morphine; examples of antiallergic agents are cromolyn and nedocromil; examples of antibiotics are cephalosporins, fusicoccin, neomycin, penicillins, pentamidine, streptomycins, sulphanilamide and tetracycline, polymyxin E, tobramycin; examples of anticholinergics are atropine, metronidazole, ipratropium bromide, oxitropium bromide, trospium chloride and thiotropium bromide; examples of antihistamines are azelastine, flutemustine and mesalamine; examples of anti-inflammatory drugs are beclomethasone, budesonide, loteprednol, dexamethasone, flunisolide, fluticasone, tipepitant, triamcinolone, mometasone; examples of antitussives are narcotine (narcotine) and narcotine (noscapine); examples of bronchodilators are bambuterol, bitolterol, cabbuterol, clenbuterol, ephedrine, epinephrine, formoterol, fenoterol, hexoprenaline, ibuterol, isoproterenol (isoprendine), isoproterenol (isoproteren0l), ipratropium, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, procaterol, reproterol, rimiterol, salbutamol, salmeterol, sulfoterol, terbutaline, tolobutenol; examples of diuretics are amiloride and furosemide; examples of enzymes are trypsin; examples of cardiovascular drugs are diltiazem and nitroglycerin; examples of hormones are cortisone, hydrocortisone and prednisolone; examples of proteins and peptides are cyclosporine, cetrorelix, glucagon and insulin. Further active substances which can be used are adrenochrome, colchicine, heparin, scopolamine. The active substances listed by way of example can be used in the form of the free base or acid or in the form of a pharmaceutically acceptable salt. Counterions that can be used include, for example, physiological alkaline earth metals or alkali metals or amines, such as acetate, benzenesulfonate, sulfonate, benzoate, bicarbonate, bitartrate, bromide, chloride, iodide, carbonate, citrate, fumarate, malate, maleate, chucking, lactate, pamoate, and sulfate. Esters such as acetates, acetonates, propionates, dipropionates, valerates may also be used.

The invention also allows the physician to adjust the dose very precisely to fit the patient over a long period of time without the need to handle the partially emptied cartridge, which would have a detrimental effect on the cost of the treatment, and without compromising compatibility with other cartridges having different metering devices, such as the cartridge of WO 97/00703.

Brief description of the drawings

Figure 1 shows a perspective view of a pharmaceutical powder cartridge according to the invention.

Fig. 2 is a plan view showing a sealing tape for a pharmaceutical powder cartridge according to the present invention.

Figure 3 shows a schematic representation of the holder structure for the metering slide in a pharmaceutical powder cartridge according to the invention.

Figure 4A shows a schematic representation of a metering slide in a pharmaceutical powder cartridge according to the present invention.

Figure 4B shows a longitudinal section of the metering slide of the pharmaceutical powder cartridge according to the invention shown in figure 4A.

Figure 5 shows a longitudinal section through a pharmaceutical powder cartridge according to the invention in an inhaler with the metering slide in an emptying position.

Figure 6 shows a longitudinal section of a pharmaceutical powder cartridge according to the invention in an inhaler with the metering slide in the full load position.

Description of the preferred exemplary embodiments

Fig. 1 shows a perspective view of a housing 11 of a pharmaceutical powder cartridge 1 according to the invention, which is replaceably inserted into a powder inhaler 2. The pharmaceutical powder cartridge 1 shown here has an edge 3 at the upper part of its housing 11, which comprises two engagement areas 4, so that the pharmaceutical powder cartridge 1 can be easily inserted into the powder inhaler 2. In the illustrated exemplary embodiment, means are also provided in rim 3 for indicating the quantity of doses of medicament remaining in reservoir 6 or which have been expelled from reservoir 6, which are located in an annular groove 5 formed therein (this means is not shown in detail), for example in the form of a foil strip, and which are provided with corresponding markings, as described in detail in WO 97/00703. The user can then read the indicia through the window 7 in the edge 3.

The rim 3 also serves to carry a lid 8 by means of which a reservoir 6 can be closed, which reservoir 6 is an integral part of the pharmaceutical powder cartridge 1. Such a lid 8 is suitably closed on a collar 10 formed in the rim 3 in a watertight manner, for example by ultrasonic welding.

Arranged below the reservoir 6 is a metering slide channel 12 in which a metering slide as a metering device is movable, which in the exemplary embodiment described here is composed of three parts, respectively called carrier 13, actual metering slide body 14 and sealing strip 15 (as shown in fig. 2,3, 4A and 4B). The metering slide is assembled as follows: the sealing strip 15 of fig. 2 is inserted into the holder 13 of fig. 3 and the holder 13 is fixed to the metering slide 14 by means of the sealing strip 15.

As is clear from fig. 1, the metering slide slot 12 has an opening 16 at one end and around this opening 16 a contact surface 17 of the sealing strip 15 of the metering slide is formed. The contact surface 17 may simultaneously act as a sealing surface and extend in a plane which is approximately perpendicular to the direction of movement of the metering slide from the full position shown in figure 6 to the empty position shown in figure 5.

The metering slider body 14 shown in fig. 4A and 4B includes a metering chamber 18 having a volume representative of the dose available for inhalation. The sealing strip 15 can be co-injected, for example by multi-component injection moulding, and for this purpose it can be made of a thermoplastic elastomer, for example. Accordingly, a sealing surface can be provided on the metering slide and this elastic sealing strip 15 can be sealed in the region of the opening 16 of the metering slide groove 12 or, more preferably, it can be injection-molded in the region of the opening 16.

The housing 11 and/or the cover 8 and/or the dosing slider body 14 may advantageously be constructed of COC by injection moulding. Suitable materials are available on the market under the trade name8007, it is a pilot-produced product of Ticona, germany.

For pharmaceutical compositions in which the powder cannot be preserved or is not preserved properly, it is also advantageous to replace one reservoir 6 with two reservoir chambers, considering that it is a mixture.

Figures 5 and 6 show a longitudinal section of a pharmaceutical powder cartridge 1 inserted into an inhaler 2. As shown in these figures, the metering slide, indicated at 9, is movable within the metering slide slot 12, at least from the full position shown in fig. 6 to the empty position shown in fig. 5.

In the fully loaded position shown in fig. 6, medicament powder may fall from the reservoir 6 into the metering chamber 18. When the metering chamber 18 is filled with medicament powder as required, the metering slide 9 may then be moved to the emptying position shown in figure 5 with the aid of coupling means in the powder inhaler, which are only schematically shown in the figures, such as those described in US5,840,279 a, and which cooperate with the holder 13.

The emptying position is reached when the metering chamber 18 is located over the emptying opening 19. When the metering slide 9 reaches this position, medicament powder may fall from the metering chamber 18 through the emptying opening 19 into, for example, a powder channel 20 of the inhaler 2.

The full position of the metering slide 9, with the metering chamber 18 below the aperture 21 on the floor of the reservoir 6, is clearly seen in figure 6. To reach the emptying position, the metering slide 9 is pushed to the left in fig. 6 until the metering chamber 18 covers the emptying opening 19 and medicament powder can fall out of it.

It is also clear from fig. 6 that the sealing strip 15 of the metering slide 9 rests on the contact surface 17 of the metering slide groove 12 and ensures a good seal, preferably with a slight elastic deformation. This is achieved by prestressing by means of resilient elastic means, in particular by means of an activation device for the metering slide 9 in the inhaler which, as soon as the medicament is expelled, suitably causes an instantaneous reverse movement of the metering slide 9 from the emptying position shown in fig. 5 to the sealing full position shown in fig. 6.

In order to provide a higher contact pressure of the sealing strip 15 of the metering slide 9 on the contact surface 17 of the metering slide groove 12 and thus a particularly reliable sealing during storage of the pharmaceutical powder cartridge according to the invention, especially before initial use in a powder inhaler, as shown somewhat to the right in fig. 6, it is advantageous to provide an additional storage state for the metering slide 9 of a filled pharmaceutical powder cartridge 1, where the metering slide 9 can be secured by means of a releasable snap connection 22 as shown. In this storage state, the sealing strip 15 of the metering slide 9 on the contact surface 17 of the metering slide groove 12 is subjected to an increased prestress.

It is also advantageous to have a shaped body 2323 on the upper part of the reservoir, which is preferably fixed in its position by a corresponding shaped edge 24, in order to avoid mechanical loading of the medicament powder. The shaped body 2323 may be produced in situ by injection molding from a mixture of a thermoplastic matrix and a desiccant. In particular, to allow the desiccant to absorb moisture present in the reservoir 6 or moisture that has permeated the metering chamber 18. The use of such a shaped body 2323 ensures that no desiccant (typically silica gel) debris can enter the drug powder, and thus ensures that no desiccant debris can enter the patient's respiratory tract. The matrix 23 may be composed of a PP matrix which does not absorb moisture by itself and which is mixed with a water-soluble compound and a drying agent (e.g., polyethylene glycol) for injection, and then the water-soluble compound is washed off. This results in a sponge-like structure with channels, which, after drying of the shaped body 23, allows a rapid moisture uptake of the silica gel (water-insoluble) by capillary condensation over a large surface area.

In order to achieve rapid moisture absorption throughout the shaped body 2323, it is also advantageous to embed suitable fibers as fillers in the mixture of desiccant and thermoplastic matrix, which fibers, by virtue of their capillary attraction, ensure rapid transport of air moisture and water into the desiccant.

The matrix 2323 may also be designed in the form of a septum which is arranged as an insert, as shown only in the embodiment of fig. 5, or in a pharmaceutical powder cartridge by multicomponent injection molding, so that it forms all or part of the inner wall of the reservoir 6.

Claims (30)

1. A pharmaceutical powder cartridge (1) for a powder inhaler for filling a drug depot with a large dose of pharmaceutical powder, having at least one reservoir (6) and an integrated metering device, the integrated metering device comprises a metering slide groove (12) and at least one metering slide (9, 13, 14), the metering slide (9, 13, 14) can be moved approximately transversely in the metering slide groove (12) at least from a full position into an empty position, said integrated metering device being approximately transverse with respect to the direction of flow of the medicament powder from said at least one reservoir (6), characterized in that the metering slide groove (12) with the at least one metering slide (9, 13, 14) is sealed off from the environment at least in the full-load position of the metering slide (9, 13, 14), and the sealing is provided by an elastic sealing strip (15).

2. A pharmaceutical powder cartridge (1) according to claim 1, characterized in that the metering slide slot (12) has an opening (16) at one end which is open to the environment, part of the metering slide (9, 13, 14) being able to pass through this opening (16), and that the contact surface (17) of the sealing strip (15) is provided around this opening (16).

3. A pharmaceutical powder cartridge (1) according to claim 2, characterized in that the metering slide (9, 13, 14) has a sealing surface in a plane which is approximately transverse with respect to its direction of movement from the full loading position to the emptying position.

4. A pharmaceutical powder cartridge (1) according to claim 1, characterized in that the metering slide (9, 13, 14) is further movable to a storage position and that the sealing strip (15) is given an elastic sealing prestress at least in this storage position of the metering slide (9, 13, 14).

5. A pharmaceutical powder cartridge (1) according to claim 4, characterised in that the metering slide (9, 13, 14) is held in the storage position by resilient means.

6. A pharmaceutical powder cartridge according to any of claims 1 to 3, characterised in that the metering means comprises at least one metering chamber (18) for carrying a predetermined quantity of powdered medicament.

7. A pharmaceutical powder cartridge according to any of claims 1 to 3, characterized in that the pharmaceutical powder cartridge has at least two reservoirs (6).

8. Pharmaceutical powder cartridge according to claim 7, characterized in that it has a metering device with a metering chamber (18) for each reservoir (6) for dispensing a predetermined amount of each pharmaceutical active substance provided in the reservoir (6).

9. A pharmaceutical powder cartridge according to any of claims 1 to 3, characterized in that the metering means of the individual pharmaceutical powder cartridges have metering chambers (18) of the same or different volumes.

10. A pharmaceutical powder cartridge according to any of claims 1 to 3, characterised in that the pharmaceutical powder cartridge (1) further comprises means for indicating the dose of medicament retained in the reservoir (6) or expelled from the reservoir (6).

11. A pharmaceutical powder cartridge (1) for a powder inhaler for a drug depot for loading large doses of pharmaceutical powder, having at least one reservoir (6) and an integrated metering device which can assume at least a fully loaded position and an emptied position and which can be moved from the fully loaded position to the emptied position, characterized in that a sealing strip (15) is provided which can substantially seal off the reservoir (6) from the environment and prevent the ingress of moisture at least in the fully loaded position of the metering device, the sealing strip (15) being elastically deformable during movement of the metering device from its emptied position to the fully loaded position without sliding of the sealing strip (15) against a sealing surface (17).

12. A pharmaceutical powder cartridge according to any of claims 1 and 11, characterised in that the sealing strip (15) is made of silicone rubber or elastomer.

13. A pharmaceutical powder cartridge according to any of claims 1 to 3 and 11, characterised in that the sealing strip (15) is formed from a thermoplastic elastomer.

14. A pharmaceutical powder cartridge according to any of claims 1 to 3 and 11, wherein the thermoplastic elastomer is a thermoplastic polyester elastomer.

15. Pharmaceutical powder cartridge (1) according to any one of claims 1 to 3 and 11, comprising a housing (11) and a lid (8) which substantially enclose said at least one reservoir (6), characterized in that the housing (11) and/or the lid (8) consist of polyvinylidene chloride, a fully or partially coated pharmaceutical compatible plastic of polyvinylidene chloride, an olefin copolymer containing heterocyclic side groups or polychlorotrifluoroethylene.

16. Pharmaceutical powder cartridge (1) according to any one of claims 1 to 3 and 11, characterised in that at least one metering slide (9, 13, 14) as a component of the metering device consists of polyvinylidene chloride, a fully or partially coated, pharmaceutically compatible plastic of polyvinylidene chloride, an olefin copolymer containing heterocyclic side groups, an at least partially oriented polypropylene or polychlorotrifluoroethylene.

17. Pharmaceutical powder cartridge (1) according to any of claims 1 to 3 and 11, characterized in that the side of the housing (11) and/or the lid (8) facing at least partly the reservoir (6) comprises a desiccant mixture embedded in a thermoplastic matrix.

18. The pharmaceutical powder cartridge (1) according to any one of claims 1 to 3 and 11, comprising at least one matrix (23) consisting of a mixture of thermoplastic matrices embedded in a desiccant.

19. The pharmaceutical powder cartridge of claim 18, wherein the desiccant is silica gel.

20. A pharmaceutical powder cartridge (1) according to claim 16, characterized in that channels are formed in the low water absorption thermoplastic matrix by dissolving the soluble co-extruded component.

21. A pharmaceutical powder cartridge (1) according to claim 17, characterized in that channels are formed in the low water absorption thermoplastic matrix by dissolving the soluble co-extruded component.

22. Pharmaceutical powder cartridge (1) for powder inhalers according to claim 16, characterised in that the moisture-absorbable fibres are embedded as a filler in a low water-absorbing thermoplastic matrix.

23. Pharmaceutical powder cartridge (1) for powder inhalers according to claim 17, characterised in that the moisture-absorbable fibres are embedded as a filler in a low water-absorbing thermoplastic matrix.

24. Pharmaceutical powder cartridge (1) as claimed in any of claims 1-3 and 11, characterized in that the mixture of a thermoplastic matrix of low water absorption and a desiccant embedded therein is designed as at least part of the inner wall of the reservoir (6) by multicomponent injection moulding in a housing (11) consisting of a substantially water-air impermeable plastic.

25. A pharmaceutical powder cartridge (1) according to any of claims 1 to 3 and 11, wherein the housing (11) and the lid (8) are sealed watertight.

26. A pharmaceutical powder cartridge (1) according to any of claims 1 to 3 and 11, characterized in that a sealing strip (15) is co-injected on the housing (11) or the metering slide (9, 13, 14).

27. An inhaler for a powdered medicament, characterised by a pharmaceutical powder cartridge as claimed in any of claims 1 to 26.

28. An inhaler for powdered medicaments, the medicament being administrable by a patient via an air stream, characterized in that it is a container for a pharmaceutical powder cartridge as claimed in claims 1 to 26.

29. A pharmaceutical powder cartridge according to any one of claims 1 to 3 and 11 containing a powder of one or more of the following active substances: analgesics, antiallergic agents, anticholinergics, antihistamines, anti-inflammatory drugs, antipyretics, steroids, antitussives, bronchodilators, diuretics, drugs acting on the cardiovascular system, hormones, proteins and peptides.

30. The pharmaceutical powder cartridge of claim 29, comprising a powder of one or more of the following active agents: antibiotics, adrenocortical hormones and enzymes.