Patent Application
20220023553
The present invention describes a novel disposable pulmonary or nasal inhaler of simple construction and operation, ease of industrial filling and low cost suitable for the delivery of very large doses of pharmaceutical compounds.
Inhalers used for the delivery of pharmaceutical compounds have become widespread, particularly powder-based inhalers which use the patient's inspiratory effort as source of energy for drug delivery, mainly for the treatment of chronic respiratory diseases such as asthma or the chronic obstructive pulmonary disease, but also for the treatment of acute conditions, such as to deliver anti-infectious drugs, rescue drugs in emergency respiratory situations and to deliver antibiotics and cancer locally to the diseased lung. In addition, the potential of the fast drug onset and lower total dose from pulmonary drug delivery by powder inhalers has also been explored for systemic drug delivery. An example of this systemic drug delivery is inhaled insulin which has been a widely known scientific and commercial breakthrough.
Presently, looking ahead to the drug development pipeline, there is growing interest in delivering very large doses of drugs from powder inhalers, a non-limiting example being in the range of 100 to 400 mg, as it is anticipated that the molecule types of the drugs used for the treatment of asthma, the chronic obstructive pulmonary disease and other respiratory conditions, shifts predominantly from highly potent, small molecules to large biopharmaceutical molecules, such as proteins, peptides, antibodies, oligonucleotides and even gene/cell/RNA based biologic compounds, which are all required to be delivered in large doses to the patients.
Moreover, these compounds (large biopharmaceutical molecules) are required to be formulated by sophisticated particle engineering technologies in carrier free, high drug load formulations and delivered very efficiently to minimize drug losses, as such biopharmaceutical molecules are extremely expensive, from multiple consecutive inhalations performed by the patient from a large powder volume filled into and made available by the inhaler, since that efficient delivery minimizes the “powdery mouth” effect, throat irritation and extensive drug losses in the upper airways.
From the above it is thus required a large dose powder inhaler, capable of delivering efficiently a drug dose in the range between 100 and 400 mg of carrier free formulations, conveniently to the patient from multiple consecutive inhalations. As such a large dose inhaler of single-use has not been presented yet, a major challenge presented to the developer is designing an inhaler that is of simple use and construction, easy to fill industrially with current, traditional powder filling technologies, and which can be manufactured in high volume at a low unit cost of goods.
There is abundant prior art in the field of single-use disposable inhalers, but a very large disposable inhaler solving the above requirements has not been provided yet. The present application is particularly directed at the inventive improvement of the inhaler described in Portuguese patent applications numbers PT103481 and PT108426, both of which are assigned to Hovione.
Previously, in PT103481, there was known a disposable inhaler comprising a body 101 including a mouthpiece 102 and a cartridge 103 mounted in an opening 104 provided in the body 101 and having at least one powder compartment 105. The powder compartment 105 had inlet holes 106 to admit air and outlet holes 107 to communicate with a body inhalation channel 108 provided in the body 101. Furthermore, the cartridge 103 was made slidable relative to the body 101 by the patient, between a first position detailed in
Previously, in PT108426, there was known an inventive improvement to the disposable inhaler disclosed in PT103481, and detailed in
However, both the constructions of the disposable inhalers described in PT103481 and PT108426, require industrial scale filling of the disposable inhaler to be setup in an inhaler disassembled configuration, as the powder volume is required to be filled into the cartridge while this cartridge is dissembled in relation to the body of the disposable inhaler, and such cartridge is positioned in an specifically designed, industrial scale capable, automated mechanical apparatus that provides sealing of the cartridge compartment inlet during filling, and then immediate displacement of the filled cartridge and mechanical assembly into the body, into the position where the compartment holes are isolated and sealed, and these filling requirements have been found to lead to additional powder losses and manufacturing complexity and cost.
We have now invented a novel large dose inhaler of single-use comprising only two components that improves the constructions of the disposable inhalers as disclosed in the prior art patent applications PT103481 and PT108426 for the delivery of up to 400 mg of inhalation powders, while maintaining an inhaler that is simple and intuitive to use and that can be manufactured at a very low cost. Furthermore, we have invented a large dose single-use (disposable) inhaler of simple use, construction and low cost that is suitable for filling in an assembled inhaler configuration which maximizes ease of industrial filling with traditional powder filling machines, and minimizes both powder filling losses and manufacturing complexity and cost, and this a highly advantageous improvement to the constructions disclosed in PT103481 (Hovione) and PT108426 (Hovione) which required filling to take place in a disassembled inhaler configuration, and this is novel.
The present invention comprises two plastic-injected components as known in the prior art patent applications PT103481 and PT108426: an inhaler body and a powder cartridge. The body and cartridge are locked together after assembly to form the integral and functional disposable inhaler.
As in disposable inhalers disclosed in the prior art Portuguese applications, PT103481 and PT108426, the inhaler body is provided with a mouthpiece or nosepiece, an opening shaped for receiving and holding in place a cartridge and an inhalation channel for providing fluid communication between the patient's mouth or nose when engaged with the mouthpiece or nosepiece and the assembled cartridge. One or more body side inlets are provided to admit air directly from the atmosphere to the inhalation channel. In addition, there is at least one body bottom opening, included in the bottom wall of the body opening shaped for receiving the cartridge, to allow the admission of air from the atmosphere into the cartridge powder compartment when the cartridge is moved into the inhalation position.
As in the prior art Portuguese applications PT103481 and PT108426, the cartridge includes at least one powder compartment, that is built or moulded into the cartridge, and which is tapered cylindrical or near-cylindrical shape with rounded extremities absent of sharp angles, such as spherical, oval and the like to minimize powder retention during and after inhalation. The cartridge comprises at least one powder compartment which is movable when mounted in the body opening. In addition, there is at least one compartment bottom inlet for admission of air that is of very small size, between 0.1 and 2 mm in width, and in one aspect 1 mm or less in width. The shape of the cartridge is tapered in the direction of the powder compartment to create a “funnel” that blocks the flow of powder under gravity and other forces. Furthermore, as known in PT103481 and PT108426, the powder compartment comprises also an outlet, normally of the same or similar diameter as the compartment itself, to allow normal filling and automated high-speed filling of the powder and to allow fluid communication with the body inhalation channel through the body bottom inhalation channel inlet when the cartridge is moved into the inhalation position.
However, the inhaler of the present application includes new features not found in the inhaler described in the prior art Portuguese patent applications PT 105065, or PT108426, or in the prior art, and these new features are now detailed.
In the inhaler of this document, the inhaler body further comprises top and bottom walls in the body opening. The top and bottom walls are shaped for receiving the cartridge and are of cylindrical or near-cylindrical shape, with round extremities absent of sharp edges, as well as comprising at least one rail, preferably located at the top body wall, to allow the cartridge of cylindrical or near-cylindrical shape to be pivoted or turned in relation to the body, from multiple initial positions of the cartridge, at which initial positions the cartridge compartment is sealed, into a final position where the cartridge compartment becomes aligned with the body inhalation channel and air inlets and outlets included in the compartment are available for air admission and in communication with the body inhalation channel.
Furthermore, the inhaler body of this document comprises a hinged or foldable lid of a snap type, included in the top, cylindrical shaped wall of the body opening shaped for receiving the cartridge, injection moulded in the same material and moulding step as the body itself. The said body top wall hinged lid is moveable or foldable from a first open position, at which first open position the cartridge is assembled into the body and the cartridge compartment bottom inlet is sealed by the body bottom wall of cylindrical shape, and which is suitable to allow easy, effective industrial scale powder filling into the sealed cartridge compartment, into a second closed position, at which second closed position the cartridge assembled into the body is sealed by the body bottom, the cylindrical shaped wall and the said closed top wall hinged lid of snap type.
The hinged or foldable lid of snap type, as described above, included in the top, cylindrical shaped wall of the body opening shaped for receiving the cartridge, in addition comprises at least one plastic recess shaped to be engageable with one or more plastic protrusions included in the cartridge, to provide the device for advancing and controlling the pivoting or turning motion of the cartridge in relation to the body and to limit its turning travel between multiple initial positions, at which each multiple initial positions each of the plurality of cartridge compartments is sealed, into a final position at which final position each of the plurality of cartridge compartments becomes aligned with the body inhalation channel and air inlets and outlets included in the compartment are available for air admission and in communication with the body inhalation channel, including a non-return device to provide a non-return interference between the cartridge and the body, once said cartridge advancement is conducted.
Moreover, in this inhaler, the bottom, cylindrical shaped wall of the body opening shaped for receiving the cartridge, comprises at least one plastic protrusion engageable with the corresponding bottom, cylindrical shaped wall of the cartridge, which provides a snap type assembly between the body and cartridge and a full mechanical locking between the same following assembly.
In this inhaler, the inhaler cartridge further comprises a cylindrical or near-cylindrical shape providing the space to accommodate a plurality of powder compartments, preferably four, eight or ten, suitable for filling, storing and delivering up to 400 mg of inhalation powders.
The inhaler cartridge further comprises top and bottom walls which are of cylindrical or near-cylindrical shape, with round extremities absent of sharp edges, and comprising at least one plastic protrusion for each of the plurality of powder compartment therein, preferably located at the top cartridge wall, engageable with the body cylindrical rail and with the top wall hinged lid plastic recess, to provide a device for advancing and controlling the pivoting or turning motion of the cartridge in relation to the body and limit its turning travel between multiple initial positions, at which multiple positions each of the plurality of cartridge compartments is sealed, into a final position, at which final position each of the plurality of cartridge compartments becomes aligned with the body inhalation channel and air inlets and outlets included in the compartment are available for air admission and in communication with the body inhalation channel, including a non-return device to provide a non-return interference between the cartridge and the body, once said cartridge advancement is conducted.
Additionally, the inhaler cartridge includes at least one cartridge hand grip or holder, preferably of cylindrical shape, or multiple hand grips spaced across the cartridge, included in the cartridge frontal wall opposing the body opening shaped for receiving the cartridge, engageable with the patient's fingers and providing the device for a comfortable, easy, low friction turning of the cartridge in relation to the body between multiple positions.
In another aspect of the inhaler of the present invention, the inventive inhaler components described above, instead of pivoting or turning about one another, can be constructed as to be operated in a straight line, linear motion, where the cartridge slides perpendicularly to the axis of the mouthpiece.
The inhaler body and the cartridge can be made by injection-moulding of any suitable material for pharmaceutical use such as polyethylene (PE), polypropylene (PP), polysulfone (PSU), acrylonitrile butadiene styrene (ABS), polymethylmetacrilate (PMMA), polycarbonate (PC), polypropilene oxide (PPO), polybutylene terephthalate (PBT) polyethylene terephthalate (PET), liquid crystal polymer (LCP), polyethyleneimine (PEI), polyphenylenesulphide (PPS). Material selection should be made to maximize compatibility with the powder to be contained and delivered, minimize retention during inhalation and degradation during storage and allow transparency if possible.
Following manufacturing, the cartridge is inserted into the body of the inhaler through the opening shaped for receiving it and the engagement of snap type between the body bottom wall protrusions and the bottom cartridge wall provides full assembly and mechanical locking between the body and the cartridge, while allowing a low friction free turning movement between the cartridge and the body for the filling process.
Following assembly, the plurality of inhaler cartridge powder compartments are available and ready to be filled by conventional powder filling equipment through the body lid of snap type described above, included in the top, cylindrical shaped wall of the body opening, which is in the opened position following injection moulding of the body, and thus allows a unit dose of inhalation powder to be dispensed into each of the plurality of powder compartments included in the cartridge, while this cartridge is turned sequentially, without mechanical constraints during the filling process.
Following filling of the cartridge, the body lid, included in the top, cylindrical shaped wall of the body opening, is moved or folded from the open position into the closed position and snapped into and against the said top wall of the body opening, providing close mechanical contact and sealing interference with each compartment outlet included in plurality of cartridge powder compartments, which provides a full compartment sealing to the unit dose in said closed lid position together with the bottom body wall, in all cartridge compartment storage positions.
In its storage position, the inhaler is desirably in a foil or aluminium pouch, or pouch or packaging of any other suitable material and under low or equilibrium humidity conditions, and the plurality of cartridge powder compartments are sealed by and between the top and bottom body walls of cylindrical or near cylindrical shape.
During use of the inhaler of the present invention, the patient removes it from its packaging and accesses the inhaler with the cartridge in the storage position. The patient then engages with the cartridge hand grip and turns and advances the first of the plurality of cartridge powder compartments into the inhalation position and, at this position, the powder compartment bottom and/or lateral air vents become aligned with the bottom and/or side openings provided in the bottom/side walls of the body opening for allowing air admission. Also, at this position, the first of the plurality of cartridge powder compartment outlet becomes aligned with the bottom inlet of the inhalation channel that is included in the top wall of the body opening.
When the cartridge has travelled into the inhalation position, the patient then inhales a first dose, according to the instructions for use, and airflow is created across the device. Air is first able travel through the body bottom and/or side air inlet and into the powder compartment through the compartment bottom and/or side inlet slit to disperse the particles there contained.
The flow of air with entrained particles then enters the body inhalation channel and the supplementary air flow provided through the body side inlets induces additional channel turbulence leading to further dispersion and deagglomeration of the particles, for entrainment and final deposition in the intended site, in the lung or in the nasal cavity, depending on the application.
Following the inhalation maneuver, the interference between the plastic protrusion included in the first and each of the plurality of powder compartments, and the plastic recess included in the body top wall prevents the mechanical return of the inhaled first cartridge powder compartment.
The patient then moves the second of the plurality of cartridge powder compartment to the inhalation position and inhales a second time, repeating the maneuver as often as there are compartments.
This novel construction allows the dispersion and deagglomeration of large dose of inhalation powders while providing an inventive assembled inhaler configuration suitable for powder filling process that minimizing drug losses, industrial complexity and manufacturing cost, while maintaining an inhaler that is simple and intuitive and maintaining the part count to two components assembled through a single and simple assembly step, and all the above features cumulative contribute to achieve a large dose inhaler manufactured at low cost, which provides an economical advantage.
Based on these advantages, it is one inventive feature of the present application that the inhaler body and cartridge are assembled prior to the powder filling into the individual cartridge compartments and the said assembled inhaler comprises an opening for filling the inhalation powder into the cartridge.
It is also an inventive feature of the present application 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 that allows the inhalation powder filling through the said opening in the inhaler assembled configuration, and the cartridge is free to advance and turn in relation to the body in said assembled inhaler configuration.
It is also an inventive feature of the present application 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, that once moved or folded, from the open position suitable for powder filling, into the closed position, snaps into and against the inhaler body and provides close contact and interference with the cartridge and such said interference provides sealing of the filled cartridge.
It is also an inventive feature of the present invention 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, that once moved or folded and snapped into the inhaler body, comprises the mechanism engaging with the cartridge for restraining and controlling the advancement and turning travel of the cartridge in relation to the body between multiple initial positions, where each of the plurality of cartridge compartments is sealed, into a final position where each of the plurality of cartridge compartments becomes aligned with the body inhalation channel and air inlets and outlets included in the compartment are available for air admission and in communication with the body inhalation channel, including the non-return device to provide a non-return mechanism between the cartridge and the body, once said cartridge advancement is concluded and the cartridge is locked and further movements is no longer possible.
The invention will now be described on the basis of the drawings. It will be understood that the embodiments and aspects of the invention described herein are only examples and do not limit the protective scope of the claims in any way. The invention is defined by the claims and their equivalents. It will be understood that features of one aspect or embodiment of the invention can be combined with a feature of a different aspect or aspects and/or embodiments of the invention.
Referring to the drawings, numbered sequentially after the word “Fig.”, like numerals indicate like parts, and each of the embodiments or aspects is identified with series of numbers where the number of hundreds is the number of the embodiment or aspect (1xx to 7xx) and the equivalent feature in each of the embodiments or aspects has the same number xx.
Referring to the drawings in
Referring to the drawings in
Referring to
Referring next to
Referring next to
Referring next to
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2019/081993 | 11/19/2019 | WO | 00 |
