WO2025032336A1

WO2025032336A1 - Cartridge and system for storing and dispensing liquid

Info

Publication number: WO2025032336A1
Application number: PCT/GB2024/052095
Authority: WO
Inventors: Svilen SAVOV; Rob SELBY; Simon Waddelow; Nigel Webb
Original assignee: Ttp Plc
Priority date: 2023-08-09
Filing date: 2024-08-08
Publication date: 2025-02-13
Also published as: GB202312174D0

Abstract

A cartridge and system for storing and dispensing liquid medicament, the cartridge comprising an outer container, a collapsible bag arranged within the outer container and configured to store liquid medicament. The cartridge further comprises a cap configured to close the outer container and the collapsible bag, wherein the cap comprises a medicament dispensing channel extending through the cap to the collapsible bag and one or more pressure equalisation channels extending through the cap to an intermediate cavity between the outer container and the collapsible bag and a seal configured to close the medicament dispensing channel and the one or more pressure equalisation channels. The cap is configured such that when the seal is broken, the contents of the collapsible bag may be dispensed and gas from the exterior of the cartridge may enter the intermediate cavity through the pressure equalisation channels.

Description

CARTRIDGE AND SYSTEM FOR STORING AND DISPENSING LIQUID

FIELD OF THE INVENTION

The present invention relates to cartridges and systems for storing and dispensing liquids. In particular, the invention is suited to be used within drug delivery systems with separate dose cartridges such as inhalers. The invention provides cartridges that are particularly stable having a long shelf-life, that are simple, safe and reliable to use, and that are economical to produce.

BACKGROUND

A common means to dispense medicaments orally and into the lungs is using an inhaler. When operated, an inhaler releases aerosolised or powdered medicaments that can be breathed by a user. For example, where a medicament is released as an aerosol, the medicament may be stored as a liquid within a cartridge. Inhalers may include replaceable cartridges that can be replaced when they become empty. Whereas other inhalers may be “single-use” being intended to be replaced as a whole when their cartridge is empty.

It is desirable that cartridges for inhalers have long shelf-lives, meaning that the length of time they can be stored after being manufactured and filled before becoming unsuitable for use is very large. Ideally, cartridges and their contents should be stable and not degrade significantly over time. It should not be possible for the contents of cartridges to easily escape or become contaminated with external substances.

Equally, it is important that cartridges can be safely inserted into inhalers and that their contents can be safely dispensed during operation of the inhalers without contamination.

However, existing cartridges and inhaler systems that meet the above requirements tend to include complicated mechanisms to access and dispense the contents of the cartridge. The mechanisms can be expensive to manufacture given the need for multiple parts. Equally, the complicated mechanisms can be prone to user error. Ease of use is particularly important for these products, since the users of an inhaler and cartridge system are often ill, elderly or infirm and may not have the strength or coordination to operate complicated systems. For example, US 10603451 B2 discloses inhalers and cartridges that include mechanisms to pierce both the cap and a base of a cartridge. The mechanisms have large numbers of parts and require significant space.

Therefore, it is desirable to provide a solution to the problems identified above. There is a need for inhalers and cartridges that are safe for users, have long shelflives, are easy and reliable to use and economic to produce.

SUMMARY OF INVENTION

According to aspects of the invention there are provided cartridges, systems and methods in accordance with the appended claims.

In accordance with an aspect of the invention there is provided a cartridge for a liquid medicament, the cartridge comprising an outer container, a collapsible bag arranged within the outer container and configured to store a liquid medicament, and wherein the cartridge further comprises a cap configured to close the outer container and the collapsible bag to prevent fluids entering or exiting the outer container or collapsible bag and wherein the cap comprises a medicament dispensing channel extending through the cap to the collapsible bag, and, one or more pressure equalisation channels extending through the cap to an intermediate cavity between the outer container and the collapsible bag, and a seal configured to close the medicament dispensing channel and the one or more pressure equalisation channels, wherein the cap is configured such that when the seal is broken, the contents of the collapsible bag may be dispensed through the medicament dispensing channel and gas from the exterior of the cartridge may enter the intermediate cavity through the one or more pressure equalisation channels to reduce a pressure differential between the interior and exterior of the cartridge. Cartridges in accordance with the invention are safe, have long shelf-lives, are easy and reliable to use and economical to produce

The cartridge includes a cap with a single seal that closes two different channels in the cartridge - the medicament dispensing channel through which medicament can be dispensed from the collapsible bag, and the pressure equalisation channel(s) which allow for the pressure inside the cartridge to remain similar to the exterior, ambient pressure as medicament is dispensed from the collapsible bag. Providing pressure equalisation channels that help equalise the pressure inside and outside the cartridge allows the contents of the collapsible bag (e.g. a liquid medicament) to be easily and smoothly dispensed. Through the inclusion of the pressure equalisation channels it will be appreciated that the cap of the cartridge is vented so as to prevent significant pressure differences between the interior and exterior of the cartridge.

The provision of one or more pressure equalisation channels allows the contents of the collapsible bag to be reliably dispensed over the lifetime of the cartridge in an inhaler. In particular, the cartridge is well suited for use with inhalers which generate negative internal pressures to draw the medicament from the cartridge. A negative pressure within the inhaler may drive air from the exterior of the inhaler into the intermediate volume around the collapsible bag, which in turn may push the contents of the collapsible bag out of the cartridge and into the inhaler so that the medicament is ready for dispensing to a user. Suitable inhalers and mechanisms by which the contents of the collapsible bag can be dispensed are discussed in more detail below.

Breaking the seal will be understood to encompass any act of creating a fluid channel from an exterior of the cartridge and the medicament dispensing channel and/or the pressure equalisation channels. In this manner the medicament dispensing channel and/or the pressure equalisation channels are opened. As such, the seal may be broken by acts such as piercing, tearing or breaching the seal or by peeling or separating the seal from the other components of the cap. Following the breaking of the seal and the opening of the channels, the contents of the cartridge may be dispensed via the medicament dispensing channel and the pressure equalisation channel is opened to the atmosphere so that pressure differentials can be relieved.

Preferably the medicament dispensing channel and the one or more pressure equalisation channels can be opened together by a single action - by breaking the seal. The cartridge is preferably configured such that on first use both the medicament dispensing channel and the pressure equalisation channels are opened simultaneously. For example, a tube or needle may be inserted through the seal, piercing the seal and opening the channels.

Therefore, opening the cartridge and dispensing medicament is particularly reliable. The user is not required to perform any additional step either on first use or during subsequent uses to equalise the pressure within the cartridge whilst its contents are dispensed. Therefore, user error is avoided. There is also no requirement for any additional components or mechanism to equalise the pressure within the cartridge. As such, the cartridge is cheap and easy to produce. Moreover, the cartridge may be made very compact and/or may be configured to store a relatively large amount of liquid medicament (i.e. a large number of doses) given its external dimensions.

Furthermore, providing a seal that closes the medicament dispensing channel and the one or more pressure equalisation channels is stable, safe and hygienic. Contaminants cannot enter the collapsible bag and the contents of the collapsible bag cannot be dispensed until the seal is removed, pierced or broken.

Herein, it will be understood that “channels” are holes or passages that extend through the cap. The medicament dispensing channel extends through the cap from the seal (when present) to the interior of the collapsible bag. Opening the cap by removing, piercing or breaking the seal forms a fluidic connection (i.e. a path along which liquids or gases may travel) between the interior of the collapsible bag and the exterior of the cartridge via the medicament dispensing channel. When inserted in an inhaler, the contents of the collapsible bag may be dispensed to a user through the medicament dispensing channel using the inhaler. The one or more pressure equalisation channels extend to the intermediate cavity, a space or volume within the cartridge between the outer container and the collapsible bag. Opening the cap by removing, piercing or breaking the seal forms a fluidic connection between the intermediate cavity and the exterior of the cartridge via the one or more pressure equalisation channels. When manufactured, the intermediate cavity may be filled by the collapsible bag. As the contents of the collapsible bag are dispensed, air may enter the intermediate cavity via the pressure equalisation channel(s). This leads the bag to collapse and the intermediate cavity to expand as the contents of the collapsible bag are dispensed.

If the intermediate cavity and pressure equalisation channels were not present, as the contents of the bag are removed, the pressure within the cartridge would be reduced. This would form a negative pressure differential between the interior of the collapsible bag and the exterior of the cartridge and act to prevent additional contents of the bag from being dispensed. This issue is resolved by the pressure equalisation channels provided in the cartridges discussed herein which allow for the contents of the cartridge to be dispensed at a low pressure differential.

By “collapsible” it will be understood that the shape of the collapsible bag may change and its internal volume reduce as its contents are dispensed. The collapsible bag may be thin-walled and/or have one or more walls formed of a flexible material. The collapsible bag may be formed of a single layer or multilayer construction. Preferably the bag may be formed of a flexible polymer. Particularly suitable materials for the bag are low density polyethylene (LDPE) and polypropylene (PP). The thickness of the bag and bag walls may be in the range from 80 to 200 micrometres and preferably in the range from 100 to 150 micrometres.

The outer container may be configured to protect the collapsible bag and the contents of the collapsible bag. The outer container may be a can or canister.

Preferably an exterior wall of the outer container is more rigid than a wall or walls of the collapsible bag. Where the outer container comprises multiple exterior walls, preferably all of these walls are more rigid than the wall(s) of the collapsible bag. Where the exterior wall or walls of the outer container are rigid, the outer container protects the collapsible bag inside from external forces and damage.

Additionally, or alternatively, preferably an exterior wall of the outer container has a lower fluid permeability than a wall or walls of the collapsible bag. Where the outer container comprises multiple exterior walls, preferably all of these walls have lower fluid permeability than the wall(s) of the collapsible bag. The use of a relatively impermeable outer container significantly increases the shelf-life of a cartridge. Whilst flexible materials such as polymers that can be used in collapsible bags are fluid-tight and will retain liquids, they tend to allow molecules such as water to slowly diffuse through. Over long periods of time a proportion of the contents of the collapsible bag will be lost. Providing an impermeable barrier around the collapsible bag - whether this be the walls of the outer container, a layer within the construction of the collapsible bag or another component between the collapsible bag and the outer container - reduces the flow of out and away from the collapsible bag. Therefore, the contents of the bag will remain stable and suitable for use for a longer time.

In particularly preferred examples, the outer container comprises one or more exterior walls formed of a metal or metal alloy. In preferred examples the outer container comprises exterior walls formed of aluminium as it is a relatively rigid, strong material with low permeability. For example, the outer container may comprise aluminium walls with a thickness in the range from 0.2 mm to 0.5 mm and preferably from 0.35 mm to 0.45 mm. In further examples, the outer container may comprise multiple layers including an impermeable liner layer to prevent the passage of fluids. The outer container is preferably formed as a closed tube, where one end of the tube is closed by the cap discussed above. In preferred examples the outer container is crimped or otherwise plastically deformed onto the cap or an internal bottle (if present) to form a fluid-tight joint during manufacture.

Preferably, the seal has a lower fluid permeability than a wall of the collapsible bag. For instance the seal may comprise a metal foil (e.g. an aluminium foil). Again, using a seal that is impermeable or relatively impermeable in comparison to flexible materials that may be suitable for use within a collapsible bag will prevent the diffusion and flow of moisture away from the collapsible bag and therefore increases the stability and shelf-life of the cartridge contents.

Preferably the seal comprises a metal foil. Metal foils have low permeability but remain easy to remove, break or pierce. For example, the seal may comprise an aluminium foil. Therefore, the cartridges have high stability, but remain easy to use. The seal may comprise a single layer or be of multi-layer construction. For example, the seal may comprise a metal or aluminium and an underlying adhesive layer used to connect the seal to the remaining components of the cap. In alternative examples the seal may be a rigid lid that may be removed or released by a user of the cartridge. In preferred examples, the seal is configured to be pierced by a tube such as a dip tube, capillary tube or needle. However, this is not essential, and, in a further example, the seal may be intended to include a pull tab to allow it to be removed from the cap or a rip tab to allow it to be broken.

In preferred examples, the cap may comprise a septum that extends across and closes the medicament dispensing channel. A septum (sometimes referred to as a rubber septum, sleeve septum, seal septum or septum seal) is a thin membrane that extends across a channel to provide a fluid-tight boundary. The septum will retain liquid within the collapsible bag before the cartridge is opened. The septum may be pierced or broken by a tube such as a needle or dip tube inserted through the medicament dispensing channel. During use, the contents of the collapsible bag may be easily dispensed through the channel within such a tube. The septum may be arranged at an opposing end of the medicament dispensing channel to the seal. The septum may comprise an indent or deliberate defect at its centre to reduce the force required to pierce the septum. In preferred examples, a portion of the seal, medicament dispensing channel and the septum may be arranged along a single line, such that the seal and septum may be easily pierced by a single tube (e.g. a dip tube or needle) inserted through the medicament dispensing channel into the collapsible bag. A septum that extends across and closes the medicament dispensing channel may reduce the risk of cross-contamination during assembly of the cartridge before the seal is applied to the cap. A further benefit of the septum is that it offers a further barrier against moisture loss from the interior of the collapsible bag. Therefore, a cartridge with these septums has a greater shelf-life.

Preferably, the septum is configured to form a fluid-tight seal around a tube inserted therethrough. Therefore, the septum will prevent the contents of the collapsible bag from leaking or escaping between the tube and the septum and/or contaminants entering the collapsible bag through a gap between the tube and septum. For example the septum may be formed of a flexible and resilient material such that it grips a tube inserted therethrough. In this manner the septum is configured to act as a gasket between the cap and the tube therethrough.

Preferably, the septum is formed of an elastomer or thermoplastic polymer. For example, the septum may be formed of a rubber. Indeed, the septum may be formed of Silicone, Neoprene, Ethylene Propylene Diene Monomer (EPDM) rubber, Butyl rubber or a Thermoplastic Elastomer (TPE). The septum may be part of a septum body overmolded to a main cap body of the cap that is formed of a rigid material and comprises the medicament dispensing channel and the one or more pressure equalisation channels. For example, the main body of the cap may be formed of a relatively rigid polymer such as Poly Propylene (PP), High Density Polyethylene (HDPE), Acetal or Polyoxymethylene (POM), Acrylonitrile Butadiene Styrene (ABS), Polyvinyl Chloride (PVC), or a Polycarbonate (PC). Overmolding helps ensure fluid-tight seals between different components of the cap since the relative positions of the components are fixed. Overmolding reduces the number of parts within the cartridge and reduces part handling during manufacture. In turn, reduced part handling leads to reduction in manufacturing time, manufacturing errors, cartridge cost and the risk of cross contamination.

Therefore, it will be appreciated that in preferred examples the septum is a pierceable elastomeric feature that protects the contents of the cartridge. The septum can be pierced when the cartridge is used for the first time to access and dispense the contents of the cartridge. Preferably the one or more pressure equalisation channels each extend from a side wall of the medicament dispensing channel to the intermediate space. Therefore, opening the medicament dispensing channel such that a fluidic connection is formed between collapsible bag and the exterior of the cartridge will also open the medicament dispensing channel such that a fluidic connection is formed between the intermediate cavity and the exterior of the cartridge through the pressure equalisation channels. This helps ensure the contents of the collapsible bag may be reliably dispensed. For example, the one or more pressure equalisation channels may each extend to the intermediate cavity from a position on a side wall of the medicament dispensing channel between a septum within the medicament dispensing channel and the seal.

Preferably wherein the maximum width of the medicament dispensing channel at each position at which the one or more pressure equalisation channels join the medicament dispensing channel is greater than the maximum width of the septum. Equally, the maximum width of the medicament dispensing channel at each position at which the one or more pressure equalisation channels join the medicament dispensing channel is preferably greater than the maximum width of a tube that is intended to be inserted through the medicament dispensing channel and the septum - i.e. the tube of an inhaler that is inserted into the collapsible bag to dispense the contents of the cartridge. Providing a medicament dispensing channel that is relatively wide at the point at which the pressure equalisation channel(s) join the medicament dispensing channel helps ensure that the openings to the pressure equalisation channel(s) are not blocked by a tube inserted through the medicament dispensing channel or any part of the seal. As such, the chance that a piece of foil is pushed into the medicament dispensing channel and blocks an opening to a pressure equalisation channel when a tube is inserted through the medicament dispensing channel is reduced.

For example, the medicament dispensing channel may have a tapered bore, such that its cross sectional area decreases from an end nearest the seal to an end at which the septum is provided. Such a taper will also help guide any tube towards the septum, ensuring that a tube can be reliably inserted through the medicament dispensing channel and into the collapsible bag in use. However, other arrangements of the medicament dispensing channel are possible. The medicament dispensing channel may have a stepped bore.

Preferably, the distance between the position at which each of said pressure equalisation channels join the side wall of the medicament dispensing channel and the end of the medicament dispensing channel nearest the seal is at least 0.5 times the maximum width of the medicament dispensing channel at the end of the medicament dispensing channel nearest the seal, more preferably at least 0.6 times, and more preferably still 0.7 times. This arrangement again helps prevent the one or more pressure equalisation channels from being unintentionally blocked when a tube is inserted through a seal into the medicament dispensing channel. Providing a relatively long medicament dispensing channel and one or more pressure equalisation channels that are positioned relatively far from the end of the medicament dispensing channel nearest the seal reduces the chance that the a part of the seal will be pushed into the medicament dispensing channel and block the opening to a pressure equalisation channel. It will be appreciated that where the medicament dispensing channel has a circular cross section the maximum width will be equal to the diameter of the channel. The position at which each of said pressure equalisation channels join the side wall of the medicament dispensing channel may be understood to be defined by the centreline of the pressure equalisation channel in question when it intersects with the side wall of the medicament dispensing channel.

Whilst in some examples the medicament dispensing channel may have a circular cross section, this is not essential and other shapes are possible. In some examples the perimeter of the medicament dispensing channel may comprise one or more grooves and/or protrusions. For example, the walls of the medicament dispensing channel may be fluted. These grooves or protrusions help prevent the seal from blocking the opening to the pressure equalisation channels.

In the examples discussed above, the pressure equalisation channels are directly fluidly connected to the medicament dispensing channel. For instance, the pressure equalisation channels may extend between the medicament dispensing channel and the intermediate channel. In this manner the pressure equalisation channels branch off from the medicament dispensing channel. However, this is not essential, and in further examples the pressure equalisation channels may be separate from the medicament dispensing channel. In these examples the medicament dispensing channel and the one or more pressure equalisation channels may each extend entirely through the cap from the seal to a side of the cap opposing the seal.

In preferred examples, a fluid path from the exterior of the cartridge to the intermediate cavity via a pressure equalisation channel comprises two or more turns of at least 75 degrees. For example, one or more bends may be formed within the pressure equalisation channel and/or the pressure equalisation channel may join the medicament dispensing channel at a substantially perpendicular angle. As such, the fluid path connecting the intermediate cavity to the exterior of the cartridge is indirect and tortuous. This arrangement helps maintain the quality of the contents of the cartridge after the cartridge is opened. The indirect and tortuous path restricts excessive transfer of gases from inside the cartridge to outside the cartridge. This acts to restrict the escape of water vapour or water molecules through the collapsible bag even after the cartridge and seal are opened. Preventing this flow of moisture away from the collapsible bag ensures the stability of the contents of the bag, and importantly helps avoids significant changes to the concentration of a medicant in the bag which can have substantial impact on the performance of the medicament.

Whilst the pressure inside and outside the cartridge can still be equalised through a fluid path with many bends, diffusion of individual molecules out of the intermediate cavity is slowed. As such, the contents of the cartridge remains stable for a longer period of time. Additionally or alternatively, if the pressure equalisation channel is narrower than the medicament dispensing channel this may not restrict the equalisation of pressure between the inside and outside of the cartridge but may prevent excessive mixture of gas between the intermediate cavity and external atmosphere around the cartridge. For example the minimum width of each pressure equalisation channel may be less than 75% of the minimum width of the medicament dispensing channel or more preferably less than 50% of the minimum width of the medicament dispensing channel. Similar to the bends discussed above, the relatively narrow pressure equalisation channel improves the usable life of the cartridge after it is opened as the contents of the collapsible bag escape slowly through the side walls of the bag.

Preferably, the cartridge further comprises a bottle arranged within the outer container, wherein the collapsible bag is arranged within the bottle and wherein the bottle comprises at least one wall that is more rigid than a wall of the collapsible bag. Therefore, the bottle offers further protection to the collapsible bag within the cartridge. Moreover, the bottle simplifies handling of the collapsible bag during manufacture. The bottle may be arranged within the intermediate cavity and the walls of the bottle may comprise one or more apertures that extend therethrough, so that there is fluidic connection between the walls of the collapsible bag and the outer container and/or the pressure equalisation channels. Therefore, the bottle can provide support to the collapsible bag without preventing the relief of pressure through the pressure equalisation channels. The bottle may be formed of a rigid polymer such as Poly Propylene (PP), High Density Polyethylene (HDPE), Acetal or Polyoxymethylene (POM), Acrylonitrile Butadiene Styrene (ABS), Polyvinyl Chloride (PVC), or a Polycarbonate (PC). Other materials may also be used.

As discussed above, the cap may comprise a main cap body that comprises the medicament dispensing channel and the one or more pressure equalisation channels. Preferably, the main cap body is formed of a substantially rigid material.

The cap may be attached to the bottle by a clip mechanism. For example, a portion of main cap body or the bottle may be configured to deform elastically to receive and hold a portion of the bottle or the main cap body, respectively. Alternatively, the main cap body and bottle may each comprise a screw thread and may be configured to screw together. Additionally or alternatively, the outer container and cap may be secured together by an adhesive.

The collapsible bag may be secured to the bottle (e.g. by overmolding, blowmolding, co-molding, an adhesive or weld) and/or secured between the bottle and the cap using the clip mechanisms discussed above. As such, there may be a layer of the bag wall sealed between the bottle and cap.

The cartridge may comprise a first elastomeric seal arranged between the cap and the bottle. The first elastomeric seal is configured to prevent liquids from entering or exiting the cartridge via the interface between the cap and the bottle. That is the first elastomeric seal preferably provides a fluid-tight seal between the cap and bottle. Elastomeric seals are also sometimes termed a gasket. For example, a main cap body and bottle may be arranged such that the first elastomeric seal is compressed therebetween (e.g. due to the action of the clip mechanism or the screwed connection). Where the collapsible bag is secured between the bottle and the cap, the first elastomeric seal and a portion of the collapsible bag may overlap and be secured together between the bottle and the cap. In this manner the collapsible bag and first elastomeric seal may be sandwiched on top of one another between the cap and the bottle. As such, the first elastomeric seal may be positioned between the cap and the bottle and in contact with the collapsible bag and the bottle or in contact with the collapsible bag and the cap.

The first elastomeric seal between the cap and bottle may be a separate component such as an O-ring. However, more preferably the first elastomeric seal is overmolded to the main cap body. Overmolding helps ensure a fluid-tight seal between the main cap body and bottle and reduces the number of parts within the cartridge.

As discussed above, the cap may also comprise an elastomeric septum. In some examples the elastomeric septum and first elastomeric seal are separate portions of a single elastomeric component. That is the septum and first elastomeric seal are formed integrally together as different parts of a single body. However, this is not essential, and the septum and first elastomeric seal may be separate components.

The cap and outer container may be attached to the outer container by a clip mechanism. For example, a portion of a cap main body or the outer container may be configured to deform elastically to receive and hold a portion of the outer container or the main cap body, respectively. Alternatively, the main cap body and the outer container may each comprise a screw thread and may be configured to screw together. In further examples, the outer container may be plastically deformed (e.g. folded or crimped) around the cap.

Preferably the cartridge further comprises a second elastomeric seal (gasket) arranged between the cap and the outer container. The second elastomeric seal may be configured to prevent fluids (i.e. liquids and gases) from entering or exiting the cartridge via the interface between the cap and the outer container. That is the second elastomeric seal preferably provides a fluid-tight seal between the cap and outer container. For example, a main cap body and the outer container may be arranged such that the second elastomeric seal is compressed therebetween. The seal prevents moisture egress from the collapsible bag which could affect the concentration of medicaments within the bag and prevents contaminants from entering the collapsible bag. Therefore, the cartridge has a particularly long shelf life.

Various arrangements of a cap, outer container and second elastomeric seal arranged therebetween are possible.

For example, a second elastomeric seal may be provided on a top surface of the cap furthest from the collapsible bag, and the outer container may be folded around the cap to compress the second elastomeric seal. This may offer a more secure connection than an elastomeric seal provided on a side surface of the cap, the side surface of the cap extending between a top surface of the cap furthest from the collapsible bag and a bottom surface of the cap nearest the collapsible bag. Where the seal for accessing the contents of the cartridge is provided on the top surface of the cap, the second elastomeric seal may be formed as an annulus around the seal.

The second elastomeric seal between the cap and outer container may be a separate component such as an O-ring. However, more preferably the second elastomeric seal is overmolded to the main cap body. Overmolding helps ensure a fluid-tight seal between the main cap body and outer container and reduces the number of parts within the cartridge.

Alternatively, a fluid-tight seal may be formed between the cap and the outer container by plastic deformation of a portion of the cap and/or outer container. Such a connection which involves plastic deformation includes crimped connections. For example, during manufacture the cap may be inserted into the outer container and compressed such that the material of the outer container and/or cap is plastically deformed such that it conforms to the shape of the cap or outer container (respectively). As such, a portion of the outer container may be crimped around the cap. Alternatively, where the cap sits over the outer container, the cap may be compressed around the outer container to form a crimped connection where the cap and/or outer container is plastically deformed to follow the shape of the other component. The crimped, plastically deformed portion may be on a side wall of the cap that extends between the top surface of the cap furthest from the collapsible bag and a bottom surface of the cap nearest the collapsible bag.

It will be understood that the connections and seals between the various components of the cartridge may be implemented in cartridges that do not include the specific caps discussed above that include seals, medicament dispending channels and pressure equalisation channels. Whilst together the passages and connections discussed above achieve synergistic effects, they may also be provided separately.

Therefore, according to comparative aspects of this disclosure, there may be provided a cartridge comprising a cap, a collapsible bag configured to receive a liquid medicament, and an outer container and/or bottle. The cap and bottle and/or outer container may be connected through any of the means described above. The cap may be configured to close the outer container and/or bottle and prevent fluids from entering or exiting the cartridge. The cap may comprise a rigid main cap body. A first elastomeric seal may be provided between the cap or the cap main body and the bottle. A second elastomeric seal may be provided between the cap or cap main body and the outer container. The first elastomeric seal may be a separate component from the cap and bottle and/or may be overmolded to the cap or bottle. The second elastomeric seal may be a separate component from the cap and outer container and/or may be overmolded to the cap or outer container. These components may offer similar advantages to the corresponding examples of the invention discussed above.

In the cartridge according to these comparative examples, a seal may close the cartridge. The cartridge may be configured such that the contents of the collapsible bag may be dispensed when the seal is removed, pierced or broken. The cartridge may comprise a valve positioned in a wall of its outer container and configured to allow gases to pass therethrough into the outer container but to prevent gases from passing therethrough out of the outer container. Such a valve may alleviate a pressure difference that would otherwise build between the interior of the cartridge and the exterior of the cartridge may be alleviated by a valve in the outer container. Alternatively, the cartridge may comprise an alternative mechanism configured to pierce the outer container such that, during use, gases may enter the outer container to reduce a pressure differential between the exterior and interior of the cartridge.

The cartridges according to these comparative aspects of the disclosure may include any of the optional or preferable features discussed above with reference to the previous aspect of the invention in any combination. These components may offer similar advantages to the corresponding examples of the invention discussed above. The cartridge may comprise a medicament dispensing channel as discussed above but no pressure equalisation channels. Alternatively, the cap of the cartridge may be pierced or removed entirely to allow access to the contents of the cartridge.

As previously described, all cartridges discussed above are well suited for use in inhalers and for dispensing liquid medicaments. In preferred examples, the collapsible bag of the cartridge contains a liquid medicament. However, alternatively, the cartridges may be supplied empty, ready for a subsequent filling operation. According to a further aspect of the invention there is provided an inhaler system including any of the cartridges in accordance with the preceding aspects of the invention.

The inhaler system may comprise any of the cartridges discussed above in reference to the preceding aspects of the invention and an inhaler body configured to receive the cartridge. These systems may offer the benefits discussed above with reference to the preceding aspects of the invention.

The inhaler body is preferably configured to detachably receive cartridges, such that cartridges may be replaced when empty. Alternatively, the inhaler and cartridge may be a single assembly, intended to be disposed of together when their contents have been dispensed.

The inhaler body may further comprise a mouthpiece configured to be inserted into the mouth of a user. Additionally, or alternatively, the inhaler body may include a nozzle for dispensing an aerosol. The inhaler system may further comprise an aerosoliser or nebuliser configured to convert the liquid from the cartridge (e.g. a liquid medicament) into an aerosol. For example the inhaler body may comprise a micronozzle (also termed a microfluidic chip) configured to generate an aerosol.

Preferably the inhaler body is configured to remove, pierce or break the seal of the cartridge and open the medicament dispensing channel and one or more pressure equalisation channels. More preferably still, the inhaler body is configured to remove, pierce or break the seal of the cartridge and open the medicament dispensing channel and one or more pressure equalisation channels when the cartridge is inserted into the inhaler and/or on first use of the cartridge. The inhaler body may be further configured to pierce or break a septum within the medicament dispensing channel, preferably when the cartridge is inserted into the inhaler and/or on first use of the cartridge.

Preferably the inhaler body comprises a tube configured to be inserted into the collapsible bag of the cartridge through the seal and the medicament dispensing channel, wherein the contents of the collapsible bag may be dispensed to a user via the tube and mouthpiece. Therefore, the contents of the collapsible bag may be dispensed via the tube and the medicament dispensing channel through which the tube extends. The tube may be configured to pierce the seal and any septum present within the medicament dispensing channel. The tube may be a dip tube, capillary tube, needle or any other suitable tube.

In some examples the tube may be cylindrical. However, in preferred examples the tube may comprise outer surface on which are formed one or more grooves or projections. For example, the tube may comprise an outer surface that is fluted or cruciform cross section. Such tubes are particularly well suited for use with cartridges and include seals formed of metal foils. When these tubes are inserted through a metal foil, the foil tends to tears in an irregular manner. This helps ensure that the foil does not block pressure equalisation channels extending through the cap. Alternatively, inhaler system may comprise an annular piercing component comprising an internal hole through which the tube extends and an external surface which comprises one or more grooves or projections. For example, the external surface of the annular piercing component may be fluted or formed as a cruciform. The inhaler system may be configured to drive the tube and annular piercing component surrounding the tube through the seal such that the tube passes through the medicament dispensing channel and into the collapsible bag. As such, the annular piercing component that surrounds the tube may ensure that the seal (e.g. a foil) tears in an irregular manner and does not block the channels extending through the cap of the cartridge.

According to further comparative examples, there may also be provided inhaler systems including any of the cartridges in accordance with the comparative examples discussed above which do not include a medicament dispensing channel or pressure relieving channels. These systems may include any or the preferable or optional features discussed above with reference to the preceding aspects of the invention.

In particular, the inhaler may comprise a tube configured to be inserted through the medicament dispensing channel and through which the contents of the collapsible bag (e.g. a medicament) may be dispensed. The inhaler may further comprise a filter configured to retain or catch contaminants or solids within a fluid passing therethrough and arranged to receive liquid from the tube. The inhaler may further comprise a micronozzle configured to receive liquid from the tube and/or filter and convert the liquid into an aerosol. For instance, the micronozzle may be configured to create two impinging jets of liquid which are directed into one another, such that the liquid is aerosolised by the contact between the jets. The inhaler may further comprise a mouthpiece through which the aerosol is dispensed. A user may breath the aerosolised liquid from the inhaler, so that the aerosol and medicament therein enters the lungs and airways of the user.

In preferred examples a user may push the cartridge into the inhaler system. This may drive an end of the tube through the seal and through the medicament dispensing channel into the collapsible bag. However, in further examples the inhaler system might comprise a tube insertion mechanism configured to drive an end of the tube through the seal and through the medicament dispensing channel. Preferably the tube insertion mechanism is configured to drive the tube through a septum closing the medicament dispensing channel (if present). For example, the inhaler body may comprise a spring mechanism configured to drive an end of the tube into the container and through the seal and any septum when released. Any other suitable mechanism may also be used.

Preferably the tube comprises a proximal end configured to be inserted into the collapsible bag and an opposing distal end, and the inhaler system further comprises a mechanism configured to generate a negative pressure at the distal end of the tube, wherein the negative pressure draws fluid from the collapsible bag into the inhaler body through the tube. Thus, distal end of the tube is a free end of the tube that is not inserted into the bag. Whilst the term negative pressure is understood as referring to a lower pressure than the ambient or environmental pressure around the inhaler.

Generating a negative pressure at the distal end of the tube may draw fluid contents of the cartridge up the tube in a priming step so that the fluid may be subsequently dispensed to a user. The movement of fluid from the cartridge may be equalised by a change in the volume of the intermediate cavity, as air from outside of the inhaler and cartridge enters the intermediate cavity via the pressure equalisation channels, replacing the contents of the cartridge which are drawn through the tube and dispensed.

To help support the flow of fluids from the cartridge, the tube may comprise or be fluidly connected to a one-way valve (also termed a non-return valve) configured to allow fluids to pass in a single direction away from the collapsible bag. As such, the one-way valve may allow the contents of the collapsible bag to exit the collapsible bag through the tube but prevent fluids from re-entering the bag. The inhaler may comprise a filter configured to filter the contents of the inhaler before they are dispensed. The filter may prevent the passage of relatively large particles and reduce the risk the inhaler is blocked. The inhaler may further comprise a micronozzle or microfluidic chip configured to convert the contents of the inhaler into an aerosol (e.g. a soft mist). For example, the micronozzle (microfluidic chip) may comprise two nozzles which create two impinging jets of fluid, which form an aerosol when they collide. The aerosol may be in the form of a soft mist (as discussed below). The inhaler may comprise a mouthpiece through which an aerosol dispensed by the inhaler may be breathed by a user.

Preferably the inhaler system is a soft mist inhaler system. A soft mist inhaler (SMI) is an inhaler which produces an aerosol (mist) that spreads out relatively slowly. The inhaler system may be configured to dispense an aerosol at 2 m/s or less when measured at a distance of 10 cm from a mouthpiece or nozzle, preferably 1.6 m/s or less and more preferably less than 1m/s and/or wherein the dispensing or nebulization of a dose takes longer than 0.7 seconds, and preferably at least 1 second.

Preferably the inhaler system is configured to dispense fluid in puffs with a volume of medicament in the range of 0.5 microlitres to 50 microlitres, more preferably 0.5 microlitres to 30 microlitres, more preferably still from 10 to 20 microliters. An intended dose of the medicament from the inhaler may comprise a single puff, or a plurality of puffs (e.g. two puffs). Preferably the inhaler is configured to dispense droplets with an average diameter in the range of 1 to 10 microns, preferably from 2 to 6 microns, and more preferably from 3 to 5 microns.

Preferably the inhaler system is a multidose inhaler system, wherein the collapsible bag of the cartridge is configured to store a plurality of doses of liquid medicament. Preferably the collapsible bag has a capacity or internal volume in the range of 0.5 to 10 millilitres, preferably in the range of 1 to 5 millilitres.

Preferably the cartridges and inhaler systems discussed above comprise a liquid medicament stored therein.

The cartridges and inhaler systems discussed above are particularly safe for users, have long shelf-lives, are easy and reliable to use, and are economic to produce.

BRIEF DESCRIPTION OF DRAWINGS

The invention will now be described in detail with reference to the following figures:

Figures 1 a, 1 b and 1 c show schematic cross sections of a cartridge in accordance with an embodiment of the invention;

Figures 2a, 2b and 2c show schematic cross sections of a further cartridge in accordance with an embodiment of the invention;

Figures 3a, 3b and 3c show schematic cross sections of a further cartridge in accordance with an embodiment of the invention;

Figures 4a and 4b show perspective cut-away views of the cartridge shown in Figures 3a to 3c; and

Figure 5 shows a schematic cross section of an inhaler system in accordance with an embodiment of the invention. DETAILED DESCRIPTION

Figures 1a, 1 b and 1c show schematic cross sections of a cartridge 1 in accordance with an embodiment the invention. The cartridge 1 is intended for storing and dispensing a liquid medicament. The cartridge 1 is configured to be used in an inhaler system such as a soft mist inhaler system. The cartridge 1 may be detachably and replaceably received by an inhaler body that is configured to receive the contents of the cartridge and dispense these contents as an aerosol.

Figure 1a shows the cartridge 1 in a closed arrangement in which it is filled and ready for use. Figure 1 b shows the filled cartridge 1 in an open arrangement after it has been opened, and is ready for use. Figure 1c shows the cartridge 1 in an open arrangement during use as its contents have been partially dispensed.

The cartridge 1 contains an outer container 11 , which may be a can or canister. Within the outer container 11 is provided a collapsible bag 12. The walls of the collapsible bag 12 are relatively flexible and can deform. The collapsible bag 12 contains a liquid 13, preferably a liquid medicament, within an internal volume.

The cartridge 1 is closed by a cap 14. As shown, the cap 14 extends across an open end of the outer container 11 and collapsible bag 12. A fluid-tight seal is provided between the cap 14 and the outer container 11 and between the cap 14 and the collapsible bag 12. As such, the cap 14 is configured to prevent fluids from entering or exiting the outer container or collapsible bag. The cap 14 may be secured to the outer container 11 and to the collapsible bag 12 by any suitable means (e.g. clip mechanism, screw threads, adhesives, etc.).

The cap 14 comprises a medicament dispensing channel 14a that extends through the cap 14 to the interior of the collapsible bag 12. The cap 14 further comprises a pressure equalisation channel 14b that extends through the cap 14 to an intermediate cavity 16. The intermediate cavity 16 is an internal volume or space between the outer container 11 and the collapsible bag 12. As shown, the collapsible bag 12 is provided within and substantially surrounded by the intermediate cavity 16 (although this is not essential). The medicament dispensing channel 14a and the pressure equalisation channel 14b each extend through the cap 14 from a top surface of the cap 14 furthest from the collapsible bag 12 to a bottom surface of the cap 14 that is nearest (adjacent) to the collapsible bag 12.

In the closed arrangement of the cartridge 1 shown in Figure 1 a, a seal 15 extends across a top surface of the cap 14 furthest from the collapsible bag 12. The seal 15 closes open ends of the medicament dispensing channel 14a and the pressure equalisation channel 14b. The seal 15 provides a fluid-tight seal to the medicament dispensing channel 14a and the pressure equalisation channel 14b. As such, in the closed arrangement shown in Figure 1a, fluids are prevented from entering or exiting the cap 14 and from entering or existing the intermediate cavity 16 and collapsible bag 12 via the pressure equalisation channel 14b and the medicament dispensing channel 14a.

The seal 15 may be broken, pierced or removed before use of the cartridge 1 - that is before the first use of the cartridge 1 . For example, as shown in Figures 1 b and 1c. The seal 15 may be removed to open the medicament dispensing channel 14a and the pressure equalisation channel 14b. This is a simple, single step to make the cartridge 1 ready for use. Indeed, it will be understood that removing the seal 15 is a single action which opens both channels.

In the open arrangement shown in Figures 1 b and 1 c, a fluidic connection exists between the exterior of the cartridge 1 and the interior of the collapsible bag via the medicament dispensing channel 14a and a fluidic connection exists between the exterior of the cartridge 1 and the intermediate cavity 16 via the pressure equalisation channel 14b.

During use, the liquid 13 contents of the cartridge 1 may be dispensed through the medicament dispensing channel 14a, as shown by arrow C in Figure 1c. Whilst gases from the exterior of the cartridge 1 may enter the intermediate cavity 16 to equalise a pressure differential between the interior and exterior of the cartridge 1 , as shown by arrow A in Figure 1c. As liquid 13 within the cartridge 1 is dispensed, the volume within the cartridge 1 that the liquid 13 once held can be replaced with gas (e.g. ambient air) from the surroundings of the cartridge 1. As such, the collapsible bag 12 will collapse, its internal volume reducing, and the intermediate cavity 16 will expand. This transition can be seen by comparing Figures 1 b and 1c. When the cartridge 1 is full the collapsible bag 12 may substantially fill the internal volume of the cartridge 1. For instance, when full, the collapsible bag 12 may fill at least 90% of the internal space within the outer container 11. Whereas the collapsible bag 12 will be collapsed or crushed by ambient pressure as its contents are dispensed. Maintaining a low pressure differential between the interior of the collapsible bag 12 and the exterior of the cartridge 1 ensures that the remaining liquid 13 within the cartridge 1 can easily be dispensed.

In other words, the cap 14 of the cartridge 1 is vented, allowing gases to enter and exit the cartridge 1 during use to prevent significant pressure differences building up between the interior and exterior of the cartridge 1 .

Figures 2a, 2b and 2c show schematic cross sections of a further cartridge 2 in accordance with a further embodiment of the invention. The cartridge 2 shares many components with the cartridge 1 shown in Figure 1 and offers many corresponding benefits. Corresponding components have had their reference signs incremented by 10 between the sets of figures.

Figure 2a shows the cartridge 2 in a closed arrangement in which it is filled and ready for use. Figure 2b shows the filled cartridge 2 in an open arrangement after it has been opened, and is ready for use. Figure 2c shows the cartridge 2 in an open arrangement during use as its contents have been partially dispensed.

As in the cartridge 1 shown in Figure 1 , the cartridge 2 of Figures 2a, 2b and 2c contains an outer container 21 , which may be a can or canister. Within the outer container 21 is provided a collapsible bag 22. The walls of the collapsible bag 22 are relatively flexible and can deform. The collapsible bag 22 contains a liquid 23, preferably a liquid medicament, within an internal volume. Extending between the collapsible bag 22 and the outer container 21 is an intermediate cavity 26. The cartridge 2 is closed by a cap 24. As in the example of Figure 1 , the cap 24 closes the outer container 21 , intermediate cavity 26 and collapsible bag 22 with a fluid- tight seal, thereby preventing liquids from entering or exiting the cartridge 2 when the cartridge 2 is closed.

The cap 24 comprises a medicament dispensing channel 24a and a pressure equalisation channel 24b closed by a seal 25.

In more detail, the cap 24 comprises a medicament dispensing channel 24a that extends through the cap 24 to the interior of the collapsible bag 22. When opened, the contents of the collapsible bag 22 may be dispensed through the medicament dispensing channel 24a. The medicament dispensing channel 24a extends through the cap 24 from a top surface of the cap 24 furthest from the collapsible bag 22 to a bottom surface of the cap 24 that is nearest (adjacent) to the collapsible bag 22.

The cap 24 further comprises a pressure equalisation channel 24b configured to allow air and other gases to enter the intermediate cavity 26 to equalise pressure inside and outside the cartridge 2 when the cartridge is opened. As will be seen, rather than extending from a top surface of the cap 24 furthest from the collapsible bag 22 to a bottom surface of the cap 24 that is nearest (adjacent) to the collapsible bag 22 (as in the example of Figure 1) the pressure equalisation channel 24b connects to and joins the medicament dispensing channel 24a. The pressure equalisation channel 24b extends from a side wall of the medicament dispensing channel 24a to the bottom surface of the cap 24 nearest the collapsible bag 22. Therefore, the pressure equalisation channel 24b and medicament dispensing channel 24a are fluidly connected. Removing, piercing or breaking the seal 25 to open the medicament dispensing channel 24a will inherently open the pressure equalisation channel 24b. This arrangement further simplifies use of the cartridge 2, making operation of an inhaler more reliable.

To operate the cartridge 2 the seal 25 is first opened. This can be achieved by removing the seal 25 from the cartridge 2 entirely as discussed above with reference to Figure 1 . However, alternatively, a hollow tube 30 may be inserted through the seal 25, through the medicament dispensing channel 24a and into the collapsible bag 22 as shown in Figures 2b and 2c. Therefore, the tube 30 pierces the seal 25. A fluid connection between the interior of the collapsible bag 22 and the exterior of the cartridge 2 is formed through the hollow bore of the tube 30 and through which the contents of the collapsible bag 22 may be dispensed. Similarly, a fluid connection is formed between the intermediate cavity 26 and the exterior of the cartridge 2 via the pressure equalisation channel 24b, the medicament dispensing channel 24a and the aperture 25a in the seal 25 formed by the tube 30. The tube may be a dip tube, capillary tube, needle or another hollow tube.

The tube 30 may be tube of an inhaler system configured to receive the cartridge 2. The inhaler system may include a tube driving mechanism configured to push the tube 30 through the seal 25 to pierce the seal. Alternatively, the tube 30 may be inserted through the seal 25 and cap 20 manually.

Inserting a tube 30 through the seal 25 reduces the risk of inadvertent contamination or leakage of the contents of the cartridge 2. The aperture in the seal is very small. Furthermore, the tube 30 is preferably inserted shortly before the cartridge 2 inhaler system is first used which again reduces the risk of contamination or leakage. As such, the cartridge 2 shown in Figure 2 is particularly safe. These risks may be further reduced by sealing the connection between the tube 30 and the cap 24 - for instance using a septum as will be discussed with reference to Figure 3 below - however this is not essential.

In use, the flow of fluid into and out of the cartridge 2 shown in Figure 2 is similar to the example discussed above in reference to Figure 1. The contents of the collapsible bag may be dispensed through the medicament dispensing channel 24a via the tube 30 as shown by arrow C' in Figure 2c. The pressure change within the cartridge 2 that would be caused by this removal of the contents of the cartridge 2 is alleviated by the flow of gas (air) into the intermediate chamber 26 via the pressure equalisation channel 24b as shown by arrow A' in Figure 2c. The collapsible bag 22 is compressed by the pressure of the gas that enters the intermediate cavity 26 and collapses and shrinks such that its internal volume reduces. This collapse and reduction in the volume of the collapsible bag 22 can be seen by comparing the shape of the collapsible bag 22 in Figures 2b and 2c.

It will be seen that the depth at which the pressure equalisation channel 24b joins the medicament dispensing channel 24a (referred to as distance d in Figure 2a) is greater than the width of the medicament dispensing channel 24a (referred to as distance w in Figure 2a). In particular, the distance d between the position at which the pressure equalisation channel 24b joins the side wall of the medicament dispensing channel 24a (based on the centreline of the pressure equalisation channel 24b) and the end of the medicament dispensing channel 24a nearest the seal 25 is approximately twice the width of the medicament dispensing channel 24a. It is also noted that the medicament dispensing channel 24a is of constant width and so its maximum width is equal to its constant width. Having the pressure equalisation channel 24b join or connect with the medicament dispensing channel 24a at a relatively large distance from the seal - at least 0.5 times the maximum width of the medicament dispensing channel 24a at the end of the medicament dispensing channel 24a nearest the seal - helps reduce the risk that the seal 25 is pushed into the medicament dispensing channel 24a and blocks the opening to the pressure equalisation channel 24b when it is pierced by the tube 30.

The pressure equalisation channel 24b is narrower than the medicament dispensing channel 24a. Specifically, the minimum width of pressure equalisation channel 24b is approximately half of the minimum width of the medicament dispensing channel 24a. In addition, the fluid path between the exterior of the cartridge 2 and the intermediate cavity 26 involves two turns of approximately 90 degrees. These features do not prevent gas from entering the intermediate cavity 26 to equalise pressure differentials, but do act to restrict mixing of gases between the exterior of the cartridge 2 and the intermediate cavity 26. Reducing this mixing helps prevent the contents of the collapsible bag 22 from escaping from the collapsible bag 22 into the intermediate cavity 26 after the seal 25 is broken or pierced.

The outer containers 11 , 21 of the cartridges 1 , 2 shown in Figures 1 and 2 may be formed of aluminium or another metal or metal alloy. For instance, the outer containers 11 , 21 may be an aluminium canister with a thickness in the range of 0.2 to 0.5 mm. Aluminium is preferred as it is substantially impervious to fluids, having a low porosity. Therefore, an aluminium outer container 11 , 21 prevents the escape of the contents of the collapsible bag 12, 22 before the cartridge 1 , 2 is opened. The cartridges 1 , 2 will have a particularly long shelf-life. Moreover, an aluminium outer container 11 , 21 will protect the collapsible bag 12, 22 therein which has flexible walls and is susceptible to damage. The outer containers 11 , 21 are therefore preferably more rigid and have a lower porosity than the collapsible bags 12, 22 which comprise flexible, thin walls which tend to leak molecules therethrough over time.

The seals 15, 25 of the cartridges 1 , 2 shown in Figures 1 and 2 may be formed of aluminium foil and/or comprise an aluminium foil layer. Again, aluminium is well suited for this use as it is substantially impervious to fluids and can help prevent the passage of liquids and gases therethrough. The cartridges 1 , 2 will have a particularly long shelf-life. The seals 15, 25 can be attached to the cartridges 1 , 2 by an adhesive or by welding, although any other suitable method may also be used.

The cartridge 1 shown in Figure 1 may be modified to incorporate any of the features of the cartridge 2 shown in Figure 2 and vice versa.

A further example of a cartridge 100 in accordance with the invention is shown in Figures 3 and 4. The cartridge 100 comprises many similar features to the examples discussed above with reference to Figures 1 and 2, operates in a corresponding manner and offers many corresponding benefits.

Figures 3a, 3b and 3c show the cartridge 100 in cross section. Figures 4a and 4b show the cartridge 100 in a perspective cut-away view. Specifically, Figures 3a and 4a show the cartridge 100 in a closed arrangement in which it is filled and ready for use. Figures 3b, 3c and 4b show the cartridge 100 during use in an open arrangement after a tube 200 has been inserted into the cartridge. Figure 3c is a modified version of Figure 3b on which a fluid path between the exterior of the cartridge 100 and an intermediate cavity within the cartridge via a pressure equalisation channel in the cap of the cartridge 100 is marked with arrows labelled with A".

The cartridge 100 contains an outer container 110, which may be a can or canister. Within the outer container 110 is provided a collapsible bag 120. The walls of the collapsible bag 120 are relatively flexible and can deform. The collapsible bag 120 is configured to receive a liquid in, preferably a liquid medicament, within an internal volume 130. In Figures 3 and 4, the cartridge 100 is shown empty, without a liquid inside the internal volume 130 for clarity. The outer container 110 is preferably formed of aluminium and its walls are preferably more rigid and less porous than the walls of the collapsible bag 120.

The cartridge 100 additionally comprises a bottle 170 provided within the outer container 110. The collapsible bag 110 is arranged within the bottle 170. The bottle is preferable formed of a rigid polymer and helps protect the collapsible bag 110 and simplify its handling during manufacture. However, in further examples cartridges may be provided without bottles.

The cartridge 100 shown in Figures 3 and 4 is closed by a cap 140. As shown, the cap 140 extends across an open end of the bottle 170 and collapsible bag 120.

The cap 140 comprises a medicament dispensing channel 141 that extends through the cap 140 to the collapsible bag 120. The cap 140 is configured such that in use when the cap is opened the contents of the collapsible bag 120 may be dispensed through the medicament dispensing channel 141.

The cap 140 further comprises two pressure equalisation channels 142 arranged symmetrically on opposing sides of the medicament dispensing channel 141 (although this is not essential and other examples may include 1 , 2, 3 or more pressure equalisation channels). The pressure equalisation channels 142 extend between a side wall of the medicament dispensing channel 141 and an intermediate cavity 160 that extends between the outer container 160 and the collapsible bag 129. Therefore, the pressure equalisation channels 142 provide a fluidic connection between the intermediate cavity 160 and the medicament dispensing channel 141. Apertures 171 are provided through the wall of the bottle 170 such that the intermediate cavity 160 extends continuously between the outer container 110 and the collapsible bag 120 and fluidic connection exists between the exteriorof the collapsible bag 120 and the pressure equalisation channels 142.

The medicament dispensing channel 141 and the pressure equalisation channels 142 in connection with the medicament dispensing channel 141 are closed by a seal 150 at an opposing side (a top side) of the cap 140 to the collapsible bag. As in the cartridge 2 described above with reference to Figures 2a to 2c, the seal 150 may be pierced, broken or removed to open the medicament dispensing channel 141 and pressure equalisation channels 142. For example, a tube 200 may be inserted through the seal 150 to pierce it. The seal may comprise an aluminium foil.

The cap 140 comprises a relatively rigid main cap body 143, that is preferably formed from a relatively rigid polymer. The medicament dispensing channel 141 and pressure equalisation channels 142 extend through the main cap body 143. The cap 140 further comprises an elastomeric body 144. The elastomeric body 144 is preferably overmoulded to the main cap body 143. However, this is not essential and in further example the elastomeric body 144 may be a separate component from the main cap body 143. The elastomeric body 144 comprises a septum 144a - a pierceable elastomeric feature - that closes the medicament dispensing channel 141. As shown the medicament dispensing channel 141 continues to extend through the elastomeric body 144 and the septum 144a is provided at the end of the medicament dispensing channel 141 closest to the collapsible bag 120 and furthest from the seal 150 (however, this is not essential). A tube 200 may be inserted through the septum 144a to pierce it. The side walls of the medicament dispensing channel 141 are tapered to guide a tube 200 to the septum 144a. The septum 144a comprises an indent - a deliberate narrowing or defect - at its centre to reduce the force required to pierce the septum 144a using a tube 200.

After the septum 144a is pierced the elastomeric body 144 and the remains of the septum 144a may remain in contact with the outer surface of the tube 200 inserted therethrough, gripping the tube 200 due to their natural resilience. Therefore, the septum 144a is configured to provide a fluid-tight seal between the cap 140 and a tube 200 inserted therethrough into the collapsible bag 120. Liquids and gases are prevented from entering or exiting the collapsible bag 120 by the interface between the septum 144a and the tube 200.

Once a tube 200 is inserted through the seal 150, medicament dispensing channel 141 and septum 144a a fluidic connection is formed between the collapsible bag 120 and the exterior of the cartridge 100 and between the intermediate cavity 160 around the collapsible bag 120 and the exterior of the cartridge 100. Therefore, the contents of the collapsible bag 120 may be dispensed through the medicament dispensing channel 141 via the tube 200 and gas from outside the cartridge 100 may enter the intermediate cavity 160 via the pressure equalisation channels 142 to reduce any pressure difference between the interior and exterior of the cartridge 100. As the contents of the collapsible bag 120 are dispensed from the cartridge 100 and gas enters the intermediate cavity 160 from the exterior of the cartridge 100, the collapsible bag 120 will reduce in volume and collapse as shown in by comparing the shape of the collapsible bag 120 in Figures 3a and 3b or Figures 4a and 4b. As previously mentioned, the fluid path that allows gas to enter the intermediate cavity 160 from the exterior of the cartridge 100 is shown by the arrows of Figure 3c.

It will be understood that again, both the medicament dispensing channel 141 and pressure equalisation channels 142 may be opened by a single action - inserting a tube 200 into the cartridge 100 as shown in Figures 3b, 3c and 4b. This may be performed immediately before the cartridge 100 is used for the first time, or as the cartridge 100 is inserted into an inhaler body ahead of use. Alternatively, the channels could also be opened by removing the seal 150 entirely from the cap 140. The side wall of the medicament dispensing channel 141 comprises two recesses 141a to which an end of the pressure equalisation channels 142 joins. The recesses 141a help ensure that the pressure equalisation channels 142 are not blocked by the seal 150 when a tube 200 is inserted into the cartridge 100. The seal 150 is unlikely to be pushed into the recesses 141a by the insertion of a tube 200.

As can be seen from Figure 3b, the fluid path between the exterior of the cartridge 100 and the intermediate cavity 160 via the pressure equalisation channels 142 is tortuous comprising multiple turns of greater than 75 degrees. In addition, the minimum width of the pressure equalisation channels 142 is less than the minimum width of the medicament dispensing channel 141. Therefore, mixing of the contents of the intermediate channel 160 and the ambient atmosphere is reduced after the cartridge 100 is opened.

The cap 140 and the bottle 170 are connected by a clip mechanism. The cap main body 143 comprises a clip protrusion 146 configured to be pushed over and grip a corresponding lip 172 at a mouth of the bottle 170 adjacent to the cap 140. During manufacture the clip protrusion 146 elastically deforms so that it may pass the lip 172 before returning to its original shape, holding the cap 140 and bottle together 170.

The cap 140 comprises a first elastomeric seal 144b (gasket) configured to provide a fluid-tight seal between the cap 140 and the bottle 170. The first elastomeric seal 144b is formed integrally as part of the elastomeric body 144. As shown, the first elastomeric seal 144b is an annular projection from the elastomeric body 144 and is positioned between the lip 172 of the bottle and an underside of the cap 140. The clip mechanism is configured to compress the first elastomeric seal 144b between the cap 140 and the bottle 170 to create a good seal.

The outer container 110 is formed around the cap 140 and bottle 170. The walls of the outer container 110 conform to the outer surface of the cap 140 and bottle 170. The cap 140 further comprises a second elastomeric seal 145 (gasket) configured to provide a fluid-tight seal between the cap 140 and the outer container 110. The second elastomeric seal 145 is an annular elastomeric material 170 provided at the top surface of the cap 140 furthest from the collapsible bag 120. The second elastomeric seal 145 surrounds the seal 150 that closes the medicament dispensing channel 141 and pressure equalisation channels 142. A portion 111 of the wall of the outer container 110 is folded over the edge of the cap 140 and into the second elastomeric seal 145. Therefore, this portion of the outer container 110 is configured to compress the second elastomeric seal 145 and form a good seal. The second elastomeric seal 145 is preferably overmolded to the main cap body 143. However, this is not essential the second elastomeric seal 145 may be separate component such as an O-ring.

In alternative examples, various other features and components are provided to attach the cap 140 to the outer container 110 and/or the bottle 170.

It will be appreciated that many of the advantageous features of the cartridge shown in Figures 3 and 4 may be incorporated into the cartridges of Figures 1 and 2, and vice versa. As in the examples of Figures 1 and 2, the cartridge 100 shown in Figures 3 and 4 comprises a vented cap cartridge that includes pressure equalisation channels that allowing gases to enter and exit the cartridge during use and thereby preventing significant pressure differences building up between the interior and exterior of the cartridge.

The cartridges described above may be used as non-replaceable cartridges within inhalers that are disposed of after use. Eqaully, all of the cartridges discussed above are well suited to be used as replaceable cartridges within inhaler systems. In particular, the cartridges are well suited for use in soft mist inhalers.

Figure 5 shows an inhaler system 300 that comprises the cartridge 100 of Figures 3 and 4 mounted within an inhaler 400. Specifically, the inhaler 400 is a soft mist inhaler. The inhaler system 300 is configured to store and dispense liquid medicament as an aerosol. The inhaler 400 comprises a main body 410 into which the cartridge 100 may be inserted. As shown, when mounted within the inhaler system 300 the cap of the cartridge is adjacent to the main body of the inhaler 400. The inhaler 400 further comprises a cartridge cover 420 that is configured to attach to the main body 410 and encloses and protects the cartridge 100 that is inserted into the inhaler 400.

The inhaler 400 further comprises a hollow tube 430 through which the contents of the cartridge 100 can be dispensed. Inserting the cartridge 100 into the inhaler 400 involves pushing a proximal end 431 of the tube 430 through the seal and septum of the cartridge 100 and into the collapsible bag within the cartridge 100. When the cartridge 100 is inserted into the inhaler 400 the cap of the cartridge 100 is received within a tensioner body 470. The cartridge 100 may be inserted manually into the inhaler 400, but this is not essential.

At a distal end 432 of the tube 430 which is opposite to the proximal end 431 there is provided a one-way valve 433 (also sometimes termed a non-return valve). As shown, the one-way valve 433 is positioned within the tube 430 and is configured to allow liquid to flow in a direction from the proximal end 431 of the tube 430 to the distal end 432 but to prevent flow of liquid in the opposite direction. In alternative examples the one-way valve 433 may be positioned elsewhere within the liquid path of the contents of the cartridge 100 out of the inhaler 400.

The inhaler 400 further comprises a filter 440 configured to receive liquid that has passed through the tube 430. The filter 440 is configured to allow liquid to pass therethrough but to prevent the passage of solid particles within the liquid. In addition, the inhaler 400 further comprises a micronozzle 450 configured to receive liquid that has passed through the filter 440 and to convert the liquid passing therethrough into an aerosol. The aerosol may then be dispensed to a user by a mouthpiece 460 which the user may insert into their mouth. The mouthpiece 460 is protected by a mouthpiece cover 461. The mouthpiece cover 461 is mounted on a hinge 462 and may rotate about the hinge 462 between open and closed positions. The mouthpiece cover 461 is shown in a closed position in Figure 5. As mentioned, the tensioner body 470 is configured to receive the cap of the cartridge 100 when the cartridge 100 is inserted into the inhaler 400. A cartridge 100 received in the inhaler 100 is locked to the tensioner body 470, the tensioner body 470 comprising a clip 473 which grips the cap of the cartridge 100. As shown in Figure 5, the tube 430 extends through the tensioner body 470 and into the cartridge 100. As will be seen, the tensioner body 470 comprises an annular piercing component 472, through which the tube 430 extends. The annular piercing component 472 is configured to enter the medicament dispensing channel of the cartridge 100 as the cartridge 100 is inserted through the seal, medicament dispensing channel and septum of the cartridge 100. The annular piercing component 470 may comprise one or more grooves or projections on its outer surface. For example, the external surface of the annular piercing component 472 may be fluted or formed as a cruciform. This annular piercing component 472 is optional but does help ensure that the seal (e.g. a foil) tears in an irregular manner and does not block the channels extending through the cap of the cartridge 100. Alternatively, the outer surface of the tube 430 may comprise one or more grooves or projections to help ensure the seal tears irregularly.

The tensioner body 470 is connected to the main body 410 of the inhaler 400 by a spring 480 which biases the tensioner body 470, the tube 430 and any cartridge 100 received in the inhaler 400 towards the mouthpiece 460 of the inhaler. The tensioner body 470 comprises an angled cam 471 which rides on a corresponding cam 411 mounted in the main body 410 of the inhaler 400. The cams 471 , 411 are configured such that when the tensioner body 470 is rotated relative to the main body 410, the angled cam 471 rides up or down the corresponding cam 411 within the main body 410 and the tensioner body 470, tube 430 and any cartridge 100 mounted in the inhaler 400 are driven away from the filter 440, micronozzle 450 and mouthpiece 460. The tensioner body 470 may be rotated relative to the main body 410 by rotating the cartridge cover 420.

Figure 5 shows the tensioner body 470, tube 430 and cartridge 100 in an initial position relatively close to the filter 440, micronozzle 450 and mouthpiece 460. A priming volume 490 between the distal end 432 of the tube 430 and the filter 400 is relatively small. During use, the inhaler 400 is primed by rotating the cartridge cover 420 and tensioner body 470. As the tensioner body 470, cartridge 100, and tube 430 move away from (downwards as shown in Figure 5) the filter 440, micronozzle 450 and mouthpiece 460 through the action of the cams. By this movement, the volume 490 between the distal end 432 of the tube 430 and the filter 440 increases. Therefore, the pressure in this volume 490 decreases below the atmospheric pressure. This negative pressure within the volume 490 draws fluid from within cartridge 100 through the tube and one-way valve 433 into the volume 490. The pressure in the cartridge 100 is equalised by flow through the pressure equalisation channels in the cap of the cartridge discussed above. It should be noted that the reduction in pressure in the volume 490 is not equalised by the flow of air through the micronozzle 450 because the fluid channels within the micronozzle are small and so the resistance to drawing air into the volume from the atmosphere is relatively high.

After priming, the inhaler 400 may be fired by releasing the tensioner body 470, cartridge 100, and tube 430. When this assembly is released, the spring 480 drives the assembly towards the mouthpiece 460 of the inhaler 400. The movement of the distal end of the tube 430 forces the fluid in volume 490 through the filter 440 and micronozzle 450 at high pressure because fluid cannot return through the one-way valve 433. As the fluid is forced through the nozzle 450 two impinging jets of fluid are formed and an aerosol mist is generated that may be breathed by a user through the mouthpiece 460. The priming step and firing step may be repeated if multiple puffs of aerosol are required to form an appropriate dose of medicant.

Inhalers and cartridges with alternative firing mechanisms are also possible.

Claims

1 . A cartridge for a liquid medicament, the cartridge comprising: an outer container; a collapsible bag arranged within the outer container and configured to store a liquid medicament; and wherein the cartridge further comprises: a cap configured to close the outer container and the collapsible bag to prevent fluids entering or exiting the outer container or collapsible bag; and wherein the cap comprises: a medicament dispensing channel extending through the cap to the collapsible bag; and, one or more pressure equalisation channels extending through the cap to an intermediate cavity between the outer container and the collapsible bag; and a seal configured to close the medicament dispensing channel and the one or more pressure equalisation channels; wherein the cap is configured such that when the seal is broken, the contents of the collapsible bag may be dispensed through the medicament dispensing channel and gas from the exterior of the cartridge may enter the intermediate cavity through the one or more pressure equalisation channels to reduce a pressure differential between the interior and exterior of the cartridge.

2. A cartridge according to claim 1 , wherein an exterior wall of the outer container is more rigid than a wall of the collapsible bag.

3. A cartridge according to any preceding claim, wherein an exterior wall of the outer container has a lower fluid permeability than a wall of the collapsible bag.

4. A cartridge according to any preceding claim, wherein the seal has a lower fluid permeability than a wall of the collapsible bag.

5. A cartridge according to any preceding claim, wherein the seal comprises a metal foil.

6. A cartridge according to any preceding claim, wherein the cap comprises a septum that extends across and closes the medicament dispensing channel, wherein the septum is configured to be pierced or broken by a tube inserted through the medicament dispensing channel.

7. A cartridge according to claim 6, wherein the septum is configured to form a fluid-tight seal around a tube inserted therethrough

8. A cartridge according to any of claims 6 to 7, wherein the septum is formed of an elastomer or thermoplastic polymer.

9. A cartridge according to any preceding claim, wherein the one or more pressure equalisation channels each extend from a side wall of the medicament dispensing channel to the intermediate cavity.

10. A cartridge according to claim 9, wherein the maximum width of the medicament dispensing channel at each position at which the one or more pressure equalisation channels join the medicament dispensing channel is greater than the maximum width of the septum.

11. A cartridge according to any of claims 9 to 10, wherein the distance between the position at which each of said pressure equalisation channels join the side wall of the medicament dispensing channel and the end of the medicament dispensing channel nearest the seal is at least 0.5 times the maximum width of the medicament dispensing channel at the end of the medicament dispensing channel nearest the seal, more preferably at least 0.6 times, and more preferably still 0.7 times.

12. A cartridge according to any preceding claim, wherein a fluid path from the exterior of the cartridge to the intermediate cavity via a pressure equalisation channel comprises two or more turns of a least 75 degrees.

13. A cartridge according to any preceding claim, further comprising a bottle arranged within the outer container, and wherein the collapsible bag is arranged within the bottle; wherein the bottle comprises at least one wall that is more rigid than a wall of the collapsible bag, and wherein preferably the bottle is arranged within the intermediate cavity and at least one wall of the bottle comprises an aperture that extends therethrough, such that there is fluidic connection between a wall of the collapsible bag and the pressure equalisation channels.

14. A cartridge according to claim 13, further comprising a first elastomeric seal arranged between the cap and the bottle and configured to prevent liquids from entering or exiting the cartridge via the interface between the cap and the bottle.

15. A cartridge according to any preceding claim, further comprising a second elastomeric seal arranged between the cap and the outer container and configured to prevent fluids from entering or exiting the cartridge via the interface between the cap and the outer container.

16. An inhaler system comprising: a cartridge according to any preceding claim; and an inhaler body configured to receive the cartridge.

17. An inhaler system according to claim 16, wherein the inhaler body is configured to remove, pierce or break the seal of the cartridge and open the medicament dispensing channel and one or more pressure equalisation channels; and wherein preferably the inhaler body is configured to remove, pierce or break the seal of the cartridge and open the medicament dispensing channel and one or more pressure equalisation channels when the cartridge is inserted into the inhaler and/or on first use of the cartridge.

18. An inhaler system according to any of claims 16 to 17, wherein the inhaler body comprises: a tube configured to be inserted into the collapsible bag of the cartridge through the seal and the medicament dispensing channel; wherein the contents of the collapsible bag may be dispensed to a user via the tube and an inhaler mouthpiece.

19. An inhaler system according to any of claims 16 to 18, wherein the tube comprises a proximal end configured to be inserted into the collapsible bag and an opposing distal end, and wherein the inhaler system further comprises a mechanism configured to generate a negative pressure at a distal end of the tube furthest from the cartridge, wherein the negative pressure draws fluid from the collapsible bag into the inhaler body through the tube.

20. An inhaler system according to any of claims 16 to 19, wherein the inhaler system is a soft mist inhaler system.