Large dose disposable inhaler and sample loading method

Abstract

A dry powder inhaler for pulmonary or nasal use includes at least an inhaler body (201) and a cartridge (203) with multiple powder compartments (205), each containing one dose of a drug. The body (201) has an opening (204) shaped to receive the cartridge (203) and a plastic body recess (215) and detent (218), allowing controlled forward and pivotal movement of the cartridge (203) relative to the body (201) for sequentially delivering each of the multiple unit doses loaded into the cartridge (205). This inhaler configuration is suitable for loading multiple unit doses into the compartments (205) while the cartridge (203) is assembled within the body (201). The present invention provides a single-use, low-cost, large-dose inhaler, improving factory filling and manufacturing costs for delivering large doses of inhaled medication.

Description

[Technical field]

[0001] The present invention describes a novel disposable pulmonary or nasal inhaler of simple construction and operation that is easy to fill in the factory and has a low cost suitable for delivering large doses of drug compounds. [Background technology]

[0002] Inhalers used for the delivery of drug compounds are widespread, especially powder-based inhalers that utilize the patient's inspiratory effort as an energy source for drug delivery, primarily for the treatment of chronic respiratory diseases such as asthma or chronic obstructive pulmonary disease, as well as for the treatment of acute diseases such as the delivery of anti-infectives and rescue drugs in emergency respiratory environments, as well as the delivery of antibiotics and cancer drugs locally to diseased lungs. In addition, the possibility of delivering drugs to the lungs by powder inhalers for systemic drug delivery, with earlier drug onset and lower total dose, is also being investigated. An example of this systemic drug delivery is insulin inhalation, which has become a widely recognized scientific and commercial breakthrough.

[0003] Looking at the current drug development pipeline, there is an increasing interest in delivering large doses of drugs via powder inhalers, such as, by way of non-limiting example, 100 mg to 400 mg, as the drug molecule types used for the treatment of asthma, chronic obstructive pulmonary disease, and other respiratory conditions are expected to transition from primarily potent small molecules to large molecules of biological drugs, such as proteins, peptides, antibodies, oligonucleotides, and even gene / cell / RNA-based biological compounds, all of which require delivery to patients in large doses.

[0004] Furthermore, these compounds (large molecule biopharmaceutical drugs) need to be formulated in carrier-free, high drug-loading formulations using sophisticated particle engineering technologies (because such particulate biopharmaceutical molecules are very expensive) and delivered very efficiently to minimize drug loss by the patient taking multiple successive inhalations from the large amounts of powder that are loaded into and made available by the inhaler (also because such efficient delivery minimizes the "powdery mouth" effect, throat irritation, and extensive drug loss in the upper airways).

[0005] In view of the above, there is therefore a need for a large dose powder inhaler that can efficiently deliver drug doses in the range of between 100 mg and 400 mg of carrier-free formulations in multiple successive inhalations in a manner convenient for the patient. Because such single-use large dose inhalers do not yet exist, a major challenge facing developers is to design an inhaler that is simple to use and construct, can be manufactured in large quantities at a low unit cost of goods, and is easy to fill in a factory using current traditional powder filling technology.

[0006] Although there is a great deal of prior art in the field of single-use disposable inhalers, a large dose disposable inhaler that solves the above-mentioned needs has not yet been provided.The present application is particularly directed to inventive improvements of the inhalers described in Portuguese patent applications PT103481 and PT108426, both assigned to Hovione.

[0007] Already known from PT103481 is a disposable inhaler comprising a body 101 with a mouthpiece 102 and a cartridge 103 placed in an opening 104 provided in the body 101, and further with at least one powder compartment 105. The powder compartment 105 has an inlet hole 106 allowing the admission of air and an outlet hole 107 communicating with a body inhalation channel 108 provided in the body 101. Furthermore, the cartridge 103 is made such that it can be slid by the patient relative to the body 101 between a first position depicted in FIG. 1a and a second position depicted in FIGS. 1b and 1c, where in the first position the inlet and outlet holes 106 and 107 of the compartment are isolated and sealed, and in the second position the inlet and outlet holes 106 and 107 of the compartment are aligned with the inhalation channel 108 of the body, thereby allowing the air flow to be dispersed and to take the powder through the mouthpiece 102 into the patient's mouth or nasal cavity and thus into the desired site of action. This configuration disclosed in PT103481 allows for a device pre-filled with a unit dose of powder that is disposable for patient convenience, simple for economic reasons, and intuitive for easy use by the patient. This disposable inhaler has been successfully marketed, but the maximum dose that can be delivered is in the range of 10-20 mg of powder.

[0008] Already with PT 108426 an inventive improvement to the disposable inhaler disclosed in PT 103481 is known, which is depicted in Figure 1d, where an additional air inlet 109 was positioned within the cartridge compartment 105 in an inventive arrangement which created new highly effective dispersion and aerosolisation dynamics leading to operation at high deliverable doses in the range of 50mg to 100mg.

[0009] However, both disposable inhaler configurations described in PT103481 and PT108426 require industrial scale loading of the disposable inhaler in a disassembled configuration, because the powder amount needs to be loaded into the cartridge with the cartridge disassembled from the disposable inhaler body, and such cartridge is placed in a specially designed industrial scalable automated machine that seals the cartridge compartment entrance during loading and thus displaces the loaded cartridge and mechanical assembly directly into the body to a fixed position where the compartment opening is isolated and sealed. These loading requirements have been found to lead to powder loss and increased manufacturing complexity and costs. Summary of the Invention [Problem to be solved by the invention]

[0010] Therefore, a new single-use large-dose inhaler has been invented, which comprises only two components, improving the configuration of the disposable inhalers disclosed in the prior art patent applications PT103481 and PT108426 for the supply of up to 400 mg of inhalation powder, while keeping the inhaler simple and intuitive to use and allowing the inhaler to be manufactured at very low cost.Furthermore, a single-use large-dose (disposable) inhaler, which is simple in its use and configuration, and low cost, suitable for filling in the assembled inhaler configuration, maximizing the ease of filling in the factory using conventional powder filling machines, minimizing both powder filling losses and manufacturing complexity and costs.This is an advantageous and significant improvement over the configurations disclosed in PT103481 (Hovione) and PT108426 (Hovione), which require filling in the disassembled configuration of the inhaler.This is novel. [Means for solving the problem]

[0011] The present invention comprises two injected plastic parts known from prior art patent applications PT 103481 and PT 108426, an inhaler body and a powder cartridge. The body and cartridge are assembled and then fixed together, thereby forming an integrated functional disposable inhaler.

[0012] Similar to the disposable inhalers disclosed in prior art Portuguese patent applications PT103481 and PT108426, the inhaler body is equipped with a mouthpiece or nosepiece, an opening shaped to receive and hold the cartridge in place, and an inhalation channel for providing fluid communication between the patient's mouth or nose and the assembled cartridge in engagement with the mouthpiece or nosepiece. One or more body side inlets are provided to allow air to enter the inhalation channel directly from the atmosphere. In addition, there is at least one body bottom opening contained in the bottom wall of the body opening shaped to receive the cartridge, thereby allowing air to enter the cartridge powder compartment from the atmosphere when the cartridge is moved to the inhalation position.

[0013] Similar to prior art Portuguese patent applications PT103481 and PT108426, the cartridge has at least one powder compartment built into or molded integrally with the cartridge, with at least one powder compartment being tapered cylindrical or approximately cylindrical with circular ends without sharp angles such as spherical and oval, thereby minimizing powder residue during and after inhalation. The cartridge is provided with at least one powder compartment that is movable when placed in the body opening. In addition, there is at least one compartment bottom inlet to allow air to enter, having a very small size with a width between 0.1 mm and 2 mm, in one embodiment less than 1 mm wide. The shape of the cartridge is tapered in the direction of the powder compartment, thereby creating a "funnel" that prevents powder from flowing due to gravity or other forces. Furthermore, as known from PT103481 and PT108426, the powder compartment further comprises an outlet, usually having a diameter the same or equivalent to that of the compartment itself, thereby allowing normal loading and automatic fast loading of powder, and further allowing fluid communication with the body intake channel through the body bottom intake channel when the cartridge is moved to the intake position.

[0014] However, the inhaler of the present application has new features which are not found in the inhalers described in Portuguese patent applications PT 105065 or PT 108426 or in the prior art. These new features are now described.

[0015] In the inhaler of this document, the inhaler body further comprises top and bottom walls within the body opening, the top and bottom walls being shaped to receive the cartridge, being cylindrical or approximately cylindrical, having rounded ends without sharp edges, and further comprising at least one rail, preferably located at the body top wall, which allows the cylindrical or approximately cylindrical cartridge to be pivoted or swiveled relative to the body from a number of initial cartridge positions to a final cartridge position, in which the cartridge compartment is sealed and in which the cartridge compartment is aligned with the body intake channel, and in which an air inlet and an air outlet included in the compartment are available for the entry of air and communicated with the body intake channel.

[0016] Furthermore, the inhaler body of this document comprises a snap-type hinged or foldable lid contained within a cylindrical top wall of a body opening shaped to receive a cartridge, injection molded from the same material and in the same molding step as the body itself, said hinged body top wall lid being movable or foldable from a first open position to a second closed position, in which a cartridge is assembled to the body and the cartridge compartment bottom entrance is sealed by the cylindrical body bottom wall, the first open position being suitable for allowing efficient and easy filling of powder into the sealed cartridge compartment on an industrial scale, and in which a cartridge assembled to the body is sealed by the body bottom, the cylindrical wall and said snap-type closed hinged top wall lid.

[0017] The above-mentioned snap-type hinged or foldable lid contained in the cylindrical top wall of the body opening shaped to receive the cartridge further comprises at least one plastic recess shaped to be engageable with one or more plastic protrusions contained in the cartridge, thereby providing a device for promoting and controlling the pivoting or pivoting motion of the cartridge relative to the body and for limiting its pivoting movement between a plurality of initial positions and a final position, in each of the plurality of initial positions each of the plurality of cartridge compartments is sealed, and in the final position each of the plurality of cartridge compartments is aligned with the body intake channel, and the air inlet and air outlet contained in the compartment are available for admitting air and are in communication with the body intake channel. After the advancement of the cartridge is completed, the device has a detent device for realizing a detent interference between the cartridge and the body.

[0018] Further, in this inhaler, the cylindrical bottom wall of the body opening shaped to receive the cartridge has at least one plastic protrusion which is engageable with a corresponding cylindrical bottom wall of the cartridge, thereby providing a snap-type assembly between the body and the cartridge and achieving a complete mechanical fixation between the body and the cartridge after assembly.

[0019] In this inhaler, the inhaler cartridge further has a cylindrical or approximately cylindrical shape providing space for receiving a plurality of powder compartments, preferably 4, 8 or 10, suitable for filling, storing and dispensing up to 400 mg of inhalation powder.

[0020] The inhaler cartridge further comprises cylindrical or approximately cylindrical top and bottom walls with rounded ends free of sharp edges, and at least one plastic protrusion for each of a plurality of powder compartments therein, preferably located at the cartridge top wall, the at least one plastic protrusion being engageable with a cylindrical body rail and a hinged top wall plastic recess, thereby providing a device for driving and controlling the pivoting or swiveling motion of the cartridge relative to the body and for limiting its swiveling movement between a plurality of initial positions and a final position, in which each of the plurality of cartridge compartments is sealed, and in which each of the plurality of cartridge compartments is aligned with the body intake channel, and an air inlet and an air outlet contained within the compartment are available for admitting air and are in communication with the body intake channel. After the advancement of the cartridge is completed, the cartridge will have a detent device for realizing a detent interference between the cartridge and the body.

[0021] Additionally, the inhaler cartridge has at least one cartridge hand grip or cartridge holder, preferably of cylindrical shape, contained in a cartridge front wall facing a body opening shaped to receive the cartridge, or a plurality of hand grips spaced apart on the cartridge, the at least one cartridge hand grip or cartridge holder or a plurality of hand grips engageable by a patient's fingers, providing a device for effortlessly and easily pivoting the cartridge relative to the body between a plurality of positions with low friction.

[0022] In another aspect of the inhaler of the present invention, the inventive inhaler components described above may be configured to be operated in a straight line linear motion, instead of pivoting or pivoting relative to one another, where the cartridge slides perpendicular to the axis of the mouthpiece.

[0023] Inhaler bodies and cartridges can be made by injection molding of any material suitable for pharmaceutical applications, such as polyethylene (PE), polypropylene (PP), polysulfone (PSU), acrylonitrile butadiene styrene (ABS), polymethyl methacrylate (PMMA), polycarbonate (PC), polypropylene oxide (PPO), polybutylene terephthalate (PBT), polyethylene terephthalate (PET), liquid crystal polymer (LCP), polyethyleneimine (PEI), polyphenylene sulfide (PPS), etc. Material selection must be made to maximize compatibility with the powder to be contained and delivered, minimize retention during inhalation, minimize degradation during storage, and allow transparency where possible.

[0024] After manufacture, the cartridge is inserted into the body of the inhaler through an opening shaped to receive the cartridge, and a snap-type engagement between a protrusion on the bottom wall of the body and the bottom wall of the cartridge provides complete assembly and mechanical fixation between the body and cartridge, while at the same time allowing low friction free pivoting movement between the cartridge and body for the filling process.

[0025] After assembly, the multiple inhaler cartridge powder compartments are available and ready to be filled by conventional powder filling equipment via the above-mentioned snap-type body lid contained in the cylindrical top wall of the body opening, which is in an open position after injection molding of the body, thus allowing the dispensing of a unit dose of inhalation powder into each of the multiple powder compartments contained within the cartridge, while the cartridge is allowed to rotate continuously without mechanical constraints during the filling process.

[0026] After filling the cartridge, a body lid contained within the cylindrical top wall of the body opening is moved or folded from an open position to a closed position and snaps into contact with said top wall of the body opening, thereby providing tight mechanical contact and sealing interference with each compartment outlet contained within the plurality of cartridge powder compartments, thereby providing complete unit-dose sealing of the compartments in conjunction with the body bottom wall in all cartridge compartment storage positions and in the lid closed position.

[0027] In its storage position, the inhaler is preferably in a foil or aluminum pouch or pouch or package of any other suitable material and is under low or constant humidity conditions, with the multiple cartridge powder compartments being enclosed between and by a cylindrical or approximately cylindrical top and bottom body walls.

[0028] During use of the inhaler of the present invention, a patient removes the inhaler from its packaging to access the inhaler with the cartridge in a storage position. The patient then contacts the cartridge hand grip to pivot and advance a first of the multiple cartridge powder compartments to an inhalation position, where the powder compartment bottom air port and / or side air port are aligned with a bottom opening and / or a side opening provided in the bottom / side wall of the body opening, thereby allowing air to enter. Furthermore, in this position, a first of the multiple cartridge powder compartment outlets is aligned with a bottom inlet of an inhalation channel contained in the top wall of the body opening.

[0029] Once the cartridge is moved to the inhalation position, the patient inhales the first dose according to the instructions for use, creating airflow across the device, where air can travel first through the body bottom air inlet and / or the body side air inlet and then through the compartment bottom entrance slit and / or the compartment side entrance slit into the powder compartment, thereby dispersing particulate matter contained therein.

[0030] The airflow loaded with the particulate matter then enters the body inlet channel, and an auxiliary airflow provided through the body side inlet induces additional channel turbulence, thereby causing further dispersion and deagglomeration of the particulate matter for entrapment and ultimate deposition in the intended area, such as the lungs or nasal cavity, depending on the application.

[0031] After an inhalation operation, interference between a plastic protrusion in the first powder compartment of each of the plurality of powder compartments and a plastic recess in the body top wall prevents mechanical return of the first cartridge powder compartment after inhalation.

[0032] The patient then moves a second of the cartridge powder compartments into inhalation position to take a second inhalation, and so on for as many compartments as there are.

[0033] This novel configuration provides an inventive assembled inhaler configuration suitable for a powder filling process that allows dispersion and deagglomeration of large doses of inhalation powder, while minimizing drug loss, industrial complexity and manufacturing costs, while maintaining an inhaler that is simple and intuitive, limiting the number of parts to two components that are assembled in one simple assembly step, all of the above features cumulatively contributing to achieving a large dose inhaler that is manufactured at low cost and provides economic benefits.

[0034] Based on these advantages, one inventive feature of the present application is that the inhaler body and cartridge are assembled prior to loading of powder into the individual cartridge compartments, and the assembled inhaler comprises an opening for loading inhalation powder into the cartridge.

[0035] Another inventive feature of the present application is that the assembled inhaler comprises a hinged or foldable lid made of the same material and manufactured in the same step as the inhaler body, which lid allows the inhalation powder to be loaded through the opening in the assembled configuration of the inhaler, and the cartridge can freely advance and pivot relative to the body in the assembled configuration of the inhaler.

[0036] Another inventive feature of the present application is that the assembled inhaler comprises a hinged or foldable lid made of the same material and manufactured in the same step as the inhaler body, which when moved or folded from an open position suitable for powder loading to a closed position, snaps into and into contact with the inhaler body, thereby coming into close contact and interference with the cartridge, such interference sealing the filled cartridge.

[0037] Another inventive feature of the invention is that the assembled inhaler comprises a hinged or foldable lid made of the same material and manufactured in the same steps as the inhaler body, which when moved or folded to snap into the inhaler body comprises a mechanism that engages the cartridge to limit and control forward and pivotal movement of the cartridge relative to the body between a plurality of initial positions in which each of a plurality of cartridge compartments is sealed and a final position in which each of a plurality of cartridge compartments is aligned with the body inlet channel and an air inlet and an air outlet contained within the compartment are available for admission of air and communicated with the body inlet channel, and a detent device for providing a detent interference between the cartridge and the body after said cartridge advancement is completed and the cartridge is fixed and unable to move further. [Brief description of the drawings]

[0038] [Figure 1a] FIG. 1 shows a prior art inhaler. [Figure 1b] FIG. 1 shows a prior art inhaler. [Figure 1c] FIG. 1 shows a prior art inhaler. [Figure 1d] FIG. 1 shows a prior art inhaler.

[0039] [Figure 2a] FIG. 2 is a perspective view of an inhaler body according to the present invention; [Figure 2b] FIG. 2 is a longitudinal cross-sectional view of an inhaler body according to the invention;

[0040] [Figure 3a] FIG. 1 is a perspective view of an inhaler cartridge according to the present invention; [Figure 3b] 1 is a longitudinal cross-sectional view of an inhaler cartridge according to the present invention;

[0041] [Figure 4a] FIG. 2 is a perspective view showing a further embodiment of an inhaler body according to the present invention; [Figure 4b] FIG. 11 is a front view showing a further embodiment of an inhaler body according to the present invention.

[0042] [Figure 5a] 11A-11C are perspective views showing further aspects of an inhaler cartridge according to the present invention; [Figure 5b] 11A-11C are perspective views showing further aspects of an inhaler cartridge according to the present invention;

[0043] [Figure 6a] FIG. 4 is a perspective view showing the inhaler body according to FIG. 2 and the inhaler cartridge according to FIG. 3 in an exploded configuration;

[0044] [Figure 6b] FIG. 4 is a perspective view showing the inhaler body according to FIG. 2 and the inhaler cartridge according to FIG. 3 after an assembly step in an assembled configuration with the hinged lid in the open position making the device available for loading with powder.

[0045] [Figure 7a] 1A-1C are perspective views of another embodiment of an inhaler body and inhaler cartridge according to the present invention in exploded and assembled configurations, respectively; [Figure 7b] 1A-1C are perspective views of another embodiment of an inhaler body and inhaler cartridge according to the present invention in exploded and assembled configurations, respectively;

[0046] [Figure 8a] FIG. 2 is a longitudinal cross-sectional view of an inhaler according to the invention during loading of powder into the powder compartments. [Figure 8b] FIG. 2 is a longitudinal cross-sectional view of an inhaler according to the invention during loading of powder into the powder compartments. [Figure 8c] FIG. 2 is a longitudinal cross-sectional view of an inhaler according to the invention during loading of powder into the powder compartments.

[0047] [Figure 8d] FIG. 2 shows a longitudinal section of an inhaler according to the invention after loading of powder into the powder compartments, when the hinged lid has been moved to a closed position. [Figure 8e] FIG. 2 shows a longitudinal section of an inhaler according to the invention after loading of powder into the powder compartments, when the hinged lid has been moved to a closed position. [Figure 8f] FIG. 2 shows a longitudinal section of an inhaler according to the invention after loading of powder into the powder compartments, when the hinged lid has been moved to a closed position.

[0048] [Figure 9] FIG. 9 is a longitudinal section view of the inhaler according to FIG. 8 after filling with powder and closing the hinged lid, when the inhaler cartridge is in the storage position.

[0049] [Figure 10] FIG. 9 is a longitudinal section view of the inhaler according to FIG. 8 after filling with powder and closing the hinged lid, when the inhaler cartridge has been moved from the storage position to the inhalation position.

[0050] [Figure 11] FIG. 1 is a schematic diagram showing a filling method. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0051] The present invention will now be described based on the drawings. It should be understood that the embodiments and aspects of the present invention described herein are merely examples and do not limit the scope of protection of the claims. The present invention is defined by the claims and their equivalents. It should be understood that one aspect or embodiment of the present invention can be combined with the features of another aspect and / or embodiment of the present invention.

[0052] Referring to the drawings, which are numbered consecutively after the word "FIG", like numerals indicate like parts, and each embodiment or aspect is identified by a series of numbers, where the hundredth digit is the embodiment or aspect number (1xx through 7xx), and equivalent features in each embodiment or aspect have an equal number of xx.

[0053] Referring to Figures 2a and 2b, there is shown an inhaler body 201 comprising a mouthpiece or nosepiece 202 for engagement with a patient's mouth or nose respectively, and an opening 204 for receiving an inhaler cartridge 203, the opening 204 having top and bottom walls 210 and 211 which are cylindrical or approximately cylindrical in shape without any sharp edges, a sidewall 226, and at least one body rail 212 for permitting pivotal or swiveling movement of the cartridge 203 relative to the body 201.

[0054] Figure 2a shows an inhaler body 201, which is injection moulded from the same material and in the same moulding step as the body 201 itself, with a powder filling opening 214 and a hinged or foldable lid 213 contained in a top wall 210 of the body opening 204. Figure 2a further shows that the hinged or foldable lid 213 further has at least one plastic body recess 215 shaped to be engageable with a corresponding cartridge protrusion 217 in the cartridge 203, thereby providing a device for propelling and controlling the pivoting or swiveling motion of the cartridge 203 relative to the body 201, which device has a detent 218 for providing a detent between the cartridge 203 and the body 201 after said propelling is completed.

[0055] FIG. 2a additionally shows that the bottom wall 211 of the body opening 204 has at least one plastic body protrusion 219 that is engageable with a corresponding bottom wall 221 of the cartridge 203, thereby achieving a snap-type assembly and mechanical fixation between the body 201 and the cartridge 203 after the above assembly.

[0056] 2b further shows that the body top wall 210 and the hinged or foldable lid 213 form a snap-type assembly 216, where the hinged or foldable lid 213 snaps into the body top wall 210 after the above assembly to provide mechanical fixation. Additionally, an opening 224 in the bottom wall 211 of the opening 204 shaped to receive the cartridge 203 is further shown, thereby allowing air to enter said opening 204 in alignment with the mouthpiece channel 208.

[0057] Referring to the drawings in Figures 3a and 3b, there is shown an inhaler cartridge 203 having a cylindrical or approximately cylindrical cartridge top 220 and bottom wall 221 without sharp edges, and a number of powder compartments 205, each of which has an inlet 206 and an outlet 207 suitable for filling, storing and delivering a powder formulation to be inhaled.

[0058] FIG. 3a further illustrates an inhaler cartridge 203 comprising at least one plastic cartridge protrusion 217 at the cartridge top wall 220 for each of a plurality of powder compartments 205, the plastic cartridge protrusion 217 being engageable with a corresponding hinged body lid plastic body recess 215 and detent 218, thereby providing a device including a detent device for providing a detent after completion of said advancement for facilitating and controlling pivoting or pivoting motion of the cartridge 203 within the body rail 212 relative to the inhaler body 201 between a plurality of positions.

[0059] FIG. 3b further shows that the inhaler cartridge 203 has at least one hand grip 222 engageable with a patient's finger, thereby providing a pivoting device for pivoting the cartridge 203 relative to the body 201 between a plurality of positions.

[0060] Referring to FIG. 4a, a second embodiment of an inhaler body 301 is shown in which a hinged or foldable lid 313 with a plastic body recess 315 and a detent 318 forms a device for controlling the advancement of the inhaler cartridge 203 and is integrated into the mouthpiece or nosepiece 302.

[0061] FIG. 4b shows a third embodiment of an inhaler body 401 in which a plastic body recess 415 and a detent 418 forming a device for controlling the advancement of the cartridge are incorporated into the inhaler body side wall 426.

[0062] Figures 5a and 5b show a second embodiment of an inhaler cartridge 503 in which a cartridge protrusion 517 is located in the front wall of each powder compartment 505 and is engageable with a corresponding body protrusion (i.e., plastic body recess 415 and detent 418) of a third embodiment of the inhaler body 401 shown in Figure 4b, thereby providing a device for propelling and controlling the pivoting or swiveling motion of the cartridge 503 relative to the body 401 between a plurality of positions by actuation of a hand grip 522 by the patient's fingers.

[0063] Referring now to Figure 6, there is shown an inhaler assembly consisting of an inhaler body 201 and an inhaler cartridge 203. Figure 6a shows that after manufacture, the inhaler cartridge 203 is inserted into the inhaler body 201 through the opening 204. Figure 6b shows that the snap-type engagement between the plastic body projection 219 and the cartridge bottom wall 221 provides a complete mechanical fixation between the inhaler body 201 and the inhaler cartridge 203 after the assembly step, while the engagement of the cartridge top wall 220 against the body rail 212 allows free pivoting movement between the inhaler cartridge 203 and the inhaler body 201.

[0064] FIG. 6b further shows that after assembly, each of the powder compartments 205 is available for filling with a unit dose of powder through the body powder filling opening 214 because the body's hinged or foldable lid 213 is in an open position from the injection molding process of the inhaler body 201 and the inhaler cartridge 203 can freely pivot continuously relative to the inhaler body 201 without mechanical constraints.

[0065] Fig. 7a further shows the assembly of the second inhaler embodiment constituted by the inhaler body 601 and the inhaler cartridge 603, in which a lateral air inlet 609 is included in each powder compartment 605 for additionally admitting air tangentially into the powder compartment 605, which leads to creating the effective dispersion and aerosolization dynamics disclosed in the above mentioned Portuguese patent application PT 103481. Fig. 7b shows that after assembly, a lateral air inlet 625 included in the inhaler body side wall 626 allows admitting air into each powder compartment 605 through the compartment lateral air inlet 609, when said powder compartment 605 reaches the inhalation position aligned with the mouthpiece channel 608.

[0066] Referring now to Figure 8, the filling of the inhaler is illustrated. Figure 8a illustrates the loading of a unit dose of powder into the first cartridge powder compartment 705 through the body powder loading opening 714 with a conventional device, with the body lid 713 in the open position. Figure 8b illustrates the pivoting of the inhaler cartridge 703 until the second powder compartment 705 is aligned with the body powder loading opening 714 and available and ready to be loaded. Additionally, Figure 8c illustrates the loading of a second unit dose of powder into the second cartridge powder compartment 705 through the powder loading opening 714 with a conventional device, with the body hinged lid 713 in the open position.

[0067] Figures 8d to 8f show that after loading of a unit dose into the last available cartridge powder compartment 705, the body lid 713 is moved or folded from the open position to the closed position and snap-fitted into and into contact with the body top wall 710 of the inhaler body 701, thereby providing close mechanical contact and sealing interference with the outlets 707 of each cartridge powder compartment 705, and at the same time providing close contact and sealing interference of the body bottom wall 711 with the cartridge powder compartment bottom inlets 706, thereby providing complete sealing of the powder compartments 705 with unit doses of powder in all cartridge compartment storage positions.

[0068] FIG. 9 shows the inhaler when a patient removes the inhaler from the packaging to access the inhaler with the inhaler cartridge 705 in the storage position, showing that each of the multiple powder compartments 705 is sealed by a bottom body wall 711, a top body wall 710, and a closed body lid 713.

[0069] 10, the inhaler is shown as a patient contacts cartridge hand grip 522 and pivots to advance a first of powder compartments 705 to an inhalation position, where cartridge powder compartment bottom inlet 706 is aligned with bottom wall opening 724, thereby allowing air to enter powder compartment 705, and cartridge powder compartment outlet 707 is aligned with mouthpiece channel 708, thereby allowing fluid communication with the patient's airway and dispersion of a unit dose of powder contained within said powder compartment 705 via the patient's inhalation effort.

[0070] Figure 11 shows an outline of a method for filling a dry powder inhaler. In a first step S1, in the assembled inhaler, a first one of the drug doses is loaded into a first one of the individual cartridge compartments 205;505;605;705 via a loading opening 214;314;414;71 in the body 213;313;413;613;713. In step S2, the cartridge compartment 205;505;605;705 is advanced to the next drug compartment loading position, and finally in S3, all cartridge compartments 205;505;605;705 are filled. In step S4, the hinged or foldable body lid 213; 313; 413; 613; 713 is closed and snapped into contact with the inhaler body 213; 313; 413; 613; 713 in step S5.

Claims

1. A dry powder inhaler suitable for pulmonary or nasal delivery, said dry powder inhaler comprising an inhaler body (201; 301; 401; 501; 601; 701) and a cartridge (203; 303; 503; 603; 703), a. said inhaler body (201; 301; 401; 501; 601; 701) comprises a mouthpiece (202; 302; 702); an inhalation channel (208; 608; 708) for providing fluid communication with a patient's mouth when engaged with said mouthpiece (202; 302; 702); a bottom inlet of said inhalation channel (208; 608; 708); a bottom inlet of said inhalation channel (208; 608; 708) for allowing air to enter directly from the atmosphere into said inhalation channel (208; 608; 708); a side inlet (223; 623; 723) for opening the cartridge (203; 303; 503; 603; 703); a body top wall (210, 710) forming an inhaler body opening (204) in said inhaler body (201; 301; 401; 501; 601; 701), a body bottom wall (211, 711) opposite said body top wall (210, 710) and a body side wall (226, 426, 626), said inhaler body opening (204) being provided between said cartridge (203; 303; 503; 603; 703) and said cartridge bottom wall (211, 711) and said cartridge side wall (226, 426, 626) facing said body top wall (210, 710); the cartridge (203; 303; 503; 603; 703) has at least one open end to allow the cartridge (203; 303; 503; 603; 703) to be placed in said inhaler body opening (204); the body bottom wall (211, 711) has a body bottom wall opening (224; 724) and one or more plastic body projections (219; 619) for engaging and securing the cartridge (203; 303; 503; 603; 703) after it is placed in said inhaler body opening (204); one or more body rails (212) within said inhaler body opening (204) shaped to receive said cartridge (203; 303; 503; 603; 703), and one or more body recesses (215; 415) and detents (218; 418) adapted to move said cartridge (203; 303; 503; 603; 703) relative to said body (201; 301; 401; 501; 601; 701); b. the cartridge (203; 303; 503; 603; 703) comprises a plurality of tapered cylindrical or generally cylindrical powder compartments (205; 505; 605; 705) formed therein for carrying a powder-based medicament; a cartridge bottom wall (221; 521; 621) engaged with the plastic body projections (219; 619) for engaging and securing the cartridge (203; 303; 503; 603; 703) after installation in the inhaler body opening (204); a cartridge top wall (220; 520) engaged with the body rail (212); and one or more cartridge projections (217; 517) which engage with the one or more plastic body recesses (215; 415) and detents (218; 418) provided in the body (201; 301; 401; 501; 601; 701) to allow movement of the cartridge (203; 303; 503; 603; 703) relative to the body (201; 301; 401; 501; 601; 701) from a storage position to an inhalation position when the cartridge (203; 303; 503; 603; 703) is placed in the inhaler body opening (204) which is shaped to receive the cartridge (203; 303; 503; 603; 703); c. the cartridge (203; 303; 503; 603; 703) comprises a plurality of powder compartments (205; 505; 605; 705), the plurality of powder compartments (205; 505; 605; 705) comprising compartment air inlets (206; 506; 606; 706) and compartment air outlets (207; 507; 607; 707), and the plurality of powder compartments (205; 505; 605; 705) are adapted to be moved from a storage position of the cartridge (203; 303; 503; 603; 703) to a storage position of the plurality of powder compartments (205; 505; 605; 705) in which no fluid communication of air is established into the plurality of powder compartments (205; 505; 605; 705); and the suction channel (208; 608; 708) are aligned to provide air fluid communication between the body bottom wall opening (224; 724) and the compartment air inlet (206; 506; 606; 706) of the aligned one of the powder compartments (205; 505; 605; 705) and between the compartment air outlet (207; 507; 607; 707) of the aligned one of the powder compartments (205; 505; 605; 705) and the bottom inlet of the suction channel (208; 608; 708), The inhaler body (201; 301; 401; 501; 601; 701) and the cartridge (203; 303; 503; 603; 703) are assembled prior to loading of powder into the individual powder compartments (205; 505; 605; 705), the assembled inhaler comprising a body loading opening (214; 314; 414; 714) for loading inhaled powder into the cartridge (203; 303; 503; 603; 703). A dry powder inhaler comprising:

2. 2. The dry powder inhaler of claim 1, wherein the inhaler body (201; 301; 401; 501; 601; 701) further comprises at least one body side air inlet (625), and each of the plurality of powder compartments (205; 505; 605; 705) comprises a powder compartment side air inlet (609), and the at least one body side air inlet (625) and the powder compartment side air inlet (609) are in communication when a corresponding one of the plurality of powder compartments (205; 505; 605; 705) and the inhalation channel (208; 608; 708) are aligned.

3. 3. The dry powder inhaler according to claim 1 or 2, characterized in that the assembled inhaler comprises a hinged or foldable lid (213; 313; 413; 613; 713) in the inhaler body (201; 301; 401; 501; 601; 701) which allows the filling of the inhalation powder through the body filling opening (214; 314; 414; 714) in the assembled configuration of the inhaler.

4. 4. The dry powder inhaler according to claim 1, characterized in that during the loading of the powder, the cartridge (203; 303; 503; 603; 703) can move forward and swivel freely and unrestrictedly relative to the body (201; 301; 401; 501; 601; 701) in the assembled inhaler configuration in order to load a unit dose of the inhalation powder into each of the plurality of powder compartments (205; 505; 605; 705).

5. 5. The dry powder inhaler according to claim 1, wherein during powder filling, each of the plurality of powder compartments (205; 505; 605; 705) is sealed by intimate contact with the body bottom wall (211, 711) in the inhaler body opening (204) shaped to receive the cartridge (203; 303; 503; 603; 703).

6. 6. A dry powder inhaler according to claim 3 and any one of claims 4 to 5 when claim 3 is taken from claim 3, characterized in that after the last unit dose of powder has been loaded into the powder compartments (205; 505; 605; 705), the hinged or foldable body lid (213; 313; 413; 613; 713) moves into the body (201; 301; 401; 501; 601; 701) and snaps into place, establishing a mechanical interference with the compartment air outlet (207; 507; 607; 707), closing the body filling opening (214; 314; 414; 714) and sealing the filled cartridge (203; 303; 503; 603; 703) by means of said mechanical interference.

7. the hinged or foldable body lid (213; 313; 413; 613; 713) comprises at least one plastic body recess (215) and detent (218) that engages with at least one compartment protrusion (217) contained within each of the plurality of powder compartments (205; 505; 605; 705) after being moved or folded into the body (201; 301; 401; 501; 601; 701) and snap-fitted, thereby facilitating the continuous advancement and retraction of the cartridge (203; 303; 503; 603; 703) relative to the body (201; 301; 401; 501; 601; 701) between a plurality of initial positions that seal each of the plurality of powder compartments (205; 505; 605; 705) to a final position; A dry powder inhaler as described in any one of claims 3 when referring to claim 2 and claims 4 to 6 when referring to claim 3 when referring to claim 2, characterized in that in the final position, each of the multiple powder compartments (205; 505; 605; 705) is aligned with the inhalation channel (208; 608; 708) and the compartment air inlet (206; 506; 606; 706), the powder compartment lateral air inlet (609) and the compartment air outlet (207; 507; 607; 707) contained in the powder compartment (205; 505; 605; 705) are available for the entry of air and are connected to the inhalation channel (208; 608; 708).

8. A dry powder inhaler as claimed in claim 3 and any one of claims 4 to 7 when claim 3 is taken as a dependency, characterized in that when the hinged or foldable body lid (213; 313; 413; 613; 713) is moved into the body (213; 313; 413; 613; 713) and snap-fitted, a detent (218) is disposed between the cartridge (203; 303; 503; 603; 703) and the body (213; 313; 413; 613; 713) upon completion of movement of each cartridge (203; 303; 503; 603; 703).

9. 9. The dry powder inhaler according to any one of the preceding claims, characterized in that the cartridge (203; 303; 503; 603; 703) comprises at least one cartridge hand grip or holder (222; 522) adapted to pivot or advance the cartridge relative to the body.

10. A method of filling a dry powder inhaler according to any one of claims 1 to 9, comprising the steps of: In the assembled inhaler, a plurality of drug doses are loaded (S1) into each individual powder compartment (205; 505; 605; 705) via body loading openings (214; 314; 414; 714) in the inhaler body (201; 301; 401; 501; 601; 701) components, advancing (S2) the powder compartment (205; 505; 605; 705) to the next drug compartment filling position until all powder compartments (205; 505; 605; 705) are filled (S3) and a hinged or foldable body lid (213; 313; 413; 613; 713) is closed (S4) and snapped (S5) into the inhaler body (201; 301; 401; 501; 601; 701); A method comprising:

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