Nasal and pulmonary drug delivery

Abstract

The present invention relates to a device 20 for delivering a drug 30 to a user via a nasal or pulmonary route. The device 20 comprises a propellant energy source 40 to deliver a drug 30, which the pr

Description

[0001] This invention relates to nasal and pulmonary drug delivery. More particularly it relates to novel drug delivery devices and methods of delivering drugs via the nasal and oral pulmonary routes. The term “drug” includes both prescription pharmaceuticals and other functional actives delived to a user. BACKGROUND

[0002] Novel Platforms for drug delivery Applications, Woodhead Publishing Series in Biomaterials, 2023, pages 568-606, teaches nasal and pulmonary drug delivery are attractive routes for the administration of a growing number of drugs for topical and systemic treatment as well as for prevention by vaccines. This is of particular interest for drugs with poor bioavailability, as the gastrointestinal passage and hepatic first pass effect can be avoided.

[0003] As outlined in a recent review article, Front Drug Delivery, 13 April 2022, Respiratory Drug Delivery, Vol 2, 2022, inhalation therapy has existed for over 2000 years.

[0004] The basic pulmonary delivery technologies that have evolved over the past half century can best be described as small personal portable aerosol generators.

[0005] They can be divided into four major classes: • Pressurised Metered Dose Inhalers (pMDI’s); • Powder Dose Inhalers (PDI’s); • Soft Mist Inhalers (SMI’s); and • Nebulisers.

[0006] They deliver drugs as: • Powders; • Suspensions, dispersions or emulsions; and • Solutions.

[0007] These technologies have: • Different operating characteristics; • Patient interface / user requirements; and • Dose limitations.

[0008] These, devices, drug forms and technologies are illustrated in Fig 1 herein (taken from the review article).

[0009] Devices and combination products according to the invention differ from these traditional nasal and pulmonary inhalers on a number of levels, and Figs 2 to 6 illustrate some prior art devices to assist in highlighting key differences. These prior art devices are however briefly identified below: Pressurised Metered Dose Inhalers (pMDIs)

[0010] A simple pressuried metered dose inhaler of the art, is illustrated in Fig 2, and comprises as the propellant power source, a liquid (and a gas headspace) which is mixed with the drug. A metered dose is delivered on actuation and the device can include a mouthpiece or a nasal adapter.The aerosol is created by expansion of the liquid propellant.

[0011] A major driver of technology in this sector has been legislation. In the mid-1990s, chlorofluorocarbon (CFC) propellants were banned due to their ozone depletion potential (Federal Register, 1994). The realization that pMDIs, then as now the mainstay of inhalation therapy, might no longer be available, sparked enormous efforts to find alternatives, as exemplified in patent filings of that period. Between 1990 and 2010, nearly 1,000 patents describing inhalation technologies were filed, compared to less than 100 in the previous two decades (Stein and Theil, 2017). However this drive for new technologies was adressed was short lived as alternative propellants were developed through significant efforts and investments and the pMDI remains the mainstay of inhalation therapy to this day,

[0012] However, the replacement for CFCs, Hydro Fluorocarbon Alkanes (HFAs) continue to be a major contributor to global warming having up to 3350 times the global warming potential (hereon GWP) of carbon dioxide. (On Drug Delivery, April 24th 2923, Issue 145, page 13). It is known that a single pMDI can release the equivalent of 25 kg of CO2 from one canister.

[0013] Indeed, England’s National Health Service (NHS) has identifed metered-dose inhalers to be responsible for 3 percent of the total emissions by the NHS and Pharmaceutical manufacturer GSK has stated that metered-dose inhalers were responsible for 45 percent of their carbon emissions.

[0014] Accordingly there remains a clear and urgent need for pMDI technologies that are more sustainable.

[0015] In light of the global warming problems associated with HFA propellants, the industry has developed alternative HFA propellants. For example HFA152a is an alternative HFA propellant which has 138 times the GWP of CO2. However the problem with such alternate propellants is that they will take extensive time and cost to re-validate. Such re-validation needs to be performed with each one of the wide range of pharmaceutical compounds they need to be reformulated with. Hence there are very large challenges with this overall reformulation approach in terms of toxicology studies, stability, extractables and leachables, propellant flammability, and how they cause changes in drug deposition to the lungs. (On Drug Delivery, April 24th 2923, Issue 145, pages 13-17).

[0016] In contrast Applicant has a unique power source, containing an aerial gas adsorbed on an adsorbent in a canister.The aerial propellant gas can aerosolise a unit dose of a powder or a liquid which are contained separate of the power source. The aerial propellant gas has zero GWP. Because the aerial propellant is simply used to entrain the drug in an air stream, there are none of the prior art problems associated with re-formulation to alternative HFA propellants. Dry Powder Inhalers (DPIs)

[0017] Dry powder inhalers take multiple forms.

[0018] Passive devices (all current commercial devices) rely on a patients inhalation efforts to entrain, disperse and deliver the powder to the airways.

[0019] Active devices employ mechanical or electrical technology, in addition to patient inhalation to entrain, disperse and deliver the powder to the airways.

[0020] Passive devices are further split into “carrier” based systems, which can deliver a single dose or multiple doses from a reservoir, and “agglomerate” based systems.

[0021] Obviously the design varies with type, but common essential features are • An inlet through which air is drawn; • A chamber, where the powdered drug is stored prior to actuation; and • An outlet from which the dose is delivered to the user.

[0022] One such prior art design is illustrated in Fig 3 which illustrates a multi-dose passive device. A significant problem with such prior passive dry powder inhalers is that the user’s inspiratory air flow varies widely across the user base. This results in a substantial lack of dosing repeatability. Furthermore, for elderly patients and paediatric patients, such users typically cannot generate sufficient inspiratory effort and coordination to trigger entrainment and deagglomeration of powder to provide the intended aerosolised dose quantity and form.

[0023] For an active device there is also provided: • An auxiliary energy source.

[0024] The majority of active devices rely on pneumatic forces arising from manually operated pumps that are primed immediately prior to inhalation with compressed air and released when the patients flow stream has been sensed by a detector incorporated into the device. Alternatively, the pneumatic source may also be actuated simultaneously with inhalation by the user.

[0025] Once such prior art design is illustrated in Fig 4. The design shown is a singledose device. This design uses a manually-powered piston pump to provide an entrainment air stream. An issue with such devices is that patients may not have sufficient dexterity or strength to prime the pump, as significant force is required to presurise a small volume of air. The pump mechanism is also complex, in order to minimise the effort required, adding significant physical size and a high cost to the device manufacture.

[0026] In contrast Applicant has as a power source, a gas adsorbed on an adsorbent in a canister. This canister provides a substantially constant pressure source and flow rate of entrainment air over the entire life of the canister. In such a way the ability to operate, complexity and repeatability problems of the prior art are addressed. The device size and complexity can be minimised. Because the Applicant’s inhaler uses a power source, the drug can be delivered to the lungs with minimal operation and inspiratory effort by the user.

[0027] The gas is stored in a canister, at a pressure of at least 2 Bar, adsorbed on an adsorbant where it is released therefrom to dispense the drug. A filter or frit ensures the adsorbant is retained in the canister and does not exit with the gas. Soft Mist Inhaler (SMIs)

[0028] A prior art soft mist inhaler, as illustrated in Fig 5, aerosolises a drug solution by pushing the drug through a “uniblock”, which comprises an extremely small orifice. A compressed spring provides the force. The dose is delivered over a longer period, typically 1.2 sec, as compared to 0.5 sec with a pMDI. One of the main problems with such devices is that they are only able to deliver a small quantity of liquids, eg typically 15 p.l (compared to e.g.25 to 100 p.l with a pMDI). In many cases it is desired to deliver much higher masses of drugs than can be solubilised in such a small liquid volume

[0029] In contrast Applicant has as a power source, a gas adsorbed on an adsorbent in a canister. This enables drugs to be delivered potentially in powder form from a capsule, which may contain at least an order of magnitude more drug (for example, contained in up to 50 mg of powder) than is possible with an SMI.

[0030] Each of the three device types described above may be used in combination with a Valved Holding Chamber (VHC) or Spacer device which hold the aerosol until inhalation. Nebuliser

[0031] A prior art nebuliser, as illustrated in Fig 6, uses a compressor to continuously aerosolise a liquid solution or suspension containing a drug, present in a reservoir, to the user. Hand held nebulisers are also used, which can use a vibrating mesh to aerosolise the liquid. Such devices are typically battery or electrically powered, and require expensive control electronics. Nebulisers do not deliver the drug in a single breath, but require several minutes to deliver the required dose with significant patient breath coordination and compliance challenges.

[0032] In contrast Applicant has as a non-electrical and portable power source, with a gas adsorbed on an adsorbent in a canister. BRIEF SUMMARY OF THE DISCLOSURE

[0033] In accordance with a first aspect of the invention there is provided a device for delivering a drug to a user via the nasal or pulmonary route wherein the device uses a propellant energy source to deliver the drug, which propellant energy source is or comprises an aerial gas that is stored in a canister, at a pressure of at least 2 Bar, adsorbed on an adsorbant where it is released therefrom to dispense the drug, which device is absent of a bag-on-valve.

[0034] Bag on valve technology, and modifications thereof, are disclosed in WO2020021473 which document is incorporated by reference.

[0035] Preferably the pressure is between 2 and 16 Bar at 25SC, more preferably still between 2 and 10 Bar and most preferably between 4 and 8 Bar.

[0036] Preferably the adsorbant is an activated carbon or a functionalised activated carbon.

[0037] The activated carbon may be prepared from one of a host of carbon sources including, among others, natural carbonaceous sources, such as peat, wood, coal, nutshell (such as coconut), petroleum coke, bone, and bamboo shoot, drupe stones and various seeds; and synthetic sources, such as poly(acrylonitrile) or phenol-formaldehyde. The carbon is activated to develop an intricate network of pores and surface area sufficient for adsorption. The pores have various sizes ranging from microporous to sub-microporous dimensions of molecular-sized entities. The larger transport pores provide access to the smaller pores in which most of the adsorption of propellant, such as gaseous species, takes place. Carbon activation is conducted with gaseous activation using steam, carbon dioxide or other gases at elevated temperatures, or chemical activation using, for example, zinc chloride or phosphoric acid. Other activation processes may be used to achieve the pore structure and surface area that provides an extensive physical adsorption property and a high volume of adsorbing porosity.

[0038] For embodiments of the invention, the activated carbon is prepared to contain a relatively high prevalence of micropores and a low enthalpy of adsorption. This is to enable a substantially maximum gas delivery. The size of the micropores ranges from about 0.5 nm to about 2.5 nm. In an embodiment, the micropores are about 1.0-2.0 nm. The enthalpy of adsorption is less than about 25 kJ (mole of adsorbate). In other words, a carbon with a high capacity uptake for the compressed gas and a iow retention (or heei) on discharge provides for the maximum gas volume delivery. For a high uptake, the activated carbon has a high concentration of micropores. For a iow retention, carbons with a low enthalpy of adsorption (for the particular gas) are selected as there is a relatively good correlation between these two variables. Unlike traditional dispensing systems that rely on adsorbed permanent gases, application of activated carbon in embodiments of the present invention enables propellant / gases to condense or immobilize resulting in increased gas storage and delivery capacity. Ordinarily, gas storage is accomplished by increasing the pressure in a fixed volume container and the amount of gas in the container, under non-extreme conditions, basically follows the ideal gas laws. Embodiments of the present container can physically deliver more gas than a non-carbon-filled container despite the volume lost to the carbon skeleton

[0039] The activated carbon can be in a variety of forms, most commonly as powdered, granular or pelleted products.

[0040] Preferably the aerial gas is air, oxygen, nitrogen, or carbon dioxide.

[0041] More preferably the aerial gas is carbon dioxide or air or oxygen enriched with carbon dioxide. The carbon dioxide provides a greater volume of gas in the container and thus a greater energy.

[0042] Preferably the device is, as recognised in the pharmaceurtical industry, a combination product comprising the device and a drug.

[0043] Preferably the device comprises a mechanism for releasing a sufficient volume of the gas propellant at a speed that delivers / aerosolizes a unit dose of drug.

[0044] Preferably the device also comprises a mechanism for releasing the unit dose of drug from a chamber from which it is delivered.

[0045] The drug is either: a) a dry powder; b) a multi-phase dispersion of a solid in a liquid or a liquid in a liquid; or c) a single-phase solution.

[0046] In a first embodiment the device is a metered dose inhaler powered by the propellant energy source.

[0047] Preferably it is an active, as opposed to passive, metered dose inhaler.

[0048] The inhaler may comprise either a mouthpiece adapter or nasal adapter depending on whether it is intended to deliver the drug via the pulmonary or nasal route.

[0049] In a second embodiment the drug is a) a dry powder and the device is a dry powder inhaler powered by the propellant energy source.

[0050] The drug may be provided in a bulk chamber or in a sealed unit dosage form, such as a blister pack or capsules, in which case the device comprises a mechanism for releasing the drug, such as a piercing mechanism.

[0051] In a third embodiment the device is a soft mist inhaler powered by the propellant energy source.

[0052] In a fourth embodiment the device is a nebuliser powered by the propellant energy source.

[0053] A device of any of the first to third embodiments may further comprise a Valved Holding Chamber (VHC) or spacer.

[0054] The devices of the first to third embodiments may also require one or more metering devices, which one or more metering devices meter the propellant energy source and / or the drug.

[0055] The invention is based around the fact that gases can be adsorbed under pressure onto an adsorbant e.g. activated carbon and the greater volumes stored create a power source that can be exploited.

[0056] Whilst all aerial gases can be adsorbed, the greater compressibility of carbon dioxide (approx. X10 when adsorbed onto activated carbon at e.g 10 bar) makes it’s use particularly attractive.

[0057] For example, a canister filled with 25 cm3 of activated carbon and charged with carbon dioxide to reach a pressure of about 10 barg. The quantity of carbon dioxide was 2.3 g (approximately 1.3 litres of gas). Filling the carbon-containing can with carbon dioxide may be achieved by using either compressed gas (or by adding a weight of solid carbon dioxide calculated to achieve the required pressure). The filled container delivered a total gaseous volume of 1.05 litres of discharge before the pressure of the container reached atmospheric pressure. This compared with only 0.13 litres of delivered gas from the same sized container charged with 10 barg of carbon dioxide, without carbon.

[0058] However, depending on the application other aerial gases such as oxygen and nitrogen (approx, x 3 when adsorbed on activated carbon at e.g.10 bar) may be used, as may e.g carbon dioxide enriched aerial gases. In this regard, by filling a canister with a greater volume of an aerial gas (by adsorbtion) one creates an energy source that can be exploited in novel designs of inhalers and nebulisers as illustrated, in the detailed description with reference to a pMDI (Fig 7).

[0059] The technology is particularly applicable to what in the pharmaceutical industry would be termed a “combination product” namely a device and drug in combination (typically the FDA approved form).

[0060] The term “drug” is defined as a pharmaceutically active component or other medically functional ingredient e.g. saline or a vaccine.

[0061] The combination product further comprises a mechanism for releasing a sufficient volume of the propellant at a speed that delivers / aerosolizes a unit dose of drug.

[0062] It may also comprises a mechanism for releasing a unit dose of drug into a chamber from which it is delivered.

[0063] The key to each device type is the use of the power source, an aerial gas adsorbed on an adsorbent in a canister.

[0064] By using such a power source benefits such as: o Compact design; o Simpler and lower cost design; o Greater consistency of discharge; and o An ability to deliver larger doses than conventionally achieved using the prior art devices may be achieved.

[0065] In accordance with a further aspect of the present invention there is provided a method for delivering a drug to a user via the nasal or pulmonary route comprising admisistering the drug from a device which uses a propellant energy source to deliver the drug, which propellant energy source is or comprises an aerial gas that is stored in a canister, at a pressure of at least 2 Bar, adsorbed on an adsorbant where it is released therefrom to dispense the drug, which device is absent of a bag-on-valve. BRIEF DESCRIPTION OF THE DRAWINGS

[0066] Embodiments of the invention are further described hereinafter with reference to the accompanying drawing, in which: Fig 1 is an illustration of a range of prior art inhalers, the drugs typically used therewith, dose range limitations and the form (powder, suspension, solution); Fig 2 is an illustrative example of a prior art pressurised metered dose inhaler, its metering valve and adapters for nasal or pulmonary delivery; Fig 3 is an illustrative example of a prior art powder inhaler device (passive) with a reservoir delivering multiple doses via a metering mechanism; Fig 4 is an illustration of an alternative prior art powder inhaler device (active) with a pump and a mechanism for piercing capsules; Fig 5 is an illustration of a prior art soft mist inhaler device and its “uniblock” component; Fig 6 is an illustration of a prior art nebuliser; Fig 7 is an illustration of an exemplary pressurised metered dose inhaler according to the invention; Figs 8 a - 8c are equilibrium adsorbtion isotherms for the gasses oxygen, nitrogen and carbon dioxide on different adsorbents including granular activated carbon (and functionalised variaents thereof); and Fig 9 is a graph illustrating the difference between a canister filed with carbon dioxide alone and one in which the carbon dioxide is adsorded onto activated carbon. DETAILED DESCRIPTION

[0067] An exemplary combination product (10) or device (20), is illustrated in Fig 7.

[0068] Whilst the illustration is of a pressurised metered dose inhaler (200) it illustrates the principle of utilising a propellant energy source (40) to deliver the drug (30), which propellant energy source (40) is or comprises an aerial gas (41) that is stored in a canister (45), at a pressure of at least 2 Bar, adsorbed on an adsorbant (42) where it is released therefrom to dispense the drug (30), which device (20) is absent of a bag-on-valve. Where the absorbant (42) is a particulate, a filter or frit (not illustrated) may be employed to ensure any particulates generated by the adsorbant do not leave the canister with the gas stream.

[0069] This principle applies to each of: • A pressurised metered dose inhaler (200); • A dry powder inhaler (300 / 400); • A soft mist inhaler (500) and • A nebuliser (600) which “generic” devices are all illustrated in Fig 1 together with information on: • Typical drug type administered with a given device; • Maximum lung dose deliverable under the current limitations of such devices; • Drug form o Solution o Suspension, dispersions or emulsions o Powder • User limitations.

[0070] The rational for the invention is further illustrated in Figs 8a-8c and Fig 9.

[0071] Fig 8a - c (taken from ASC Omega 2022, 7, 18409-18428) compares the equilibrium adsorption isotherms of respectively: • Oxygen • Nitrogen; and • Carbon dioxide at 25SC and pressures of from 1 to 10 bar for different adsorbents including granulated activated carbon (GAC) -Pure (and functionalised). What it shows is that significant adsorption can be achieved for each of these gases, with the greatest adsorbtion being for carbon dioxide. It is a fact that one can adsorb and then release significant volumes of these aerial gases from a canister under pressure that allows it to be used as a propellant energy source (40), Such an energy source retains relatively constant pressure over the life of the canister as illustrated in Fig 9.The different gases can be used alone or in combination.

[0072] Fig 9, from WO2008064293, compares the content discharge from a canister of carbon dioxide when adsorbed v as a compressed gas. What it demonstrates is that an adsorbed gas makes it easier to manage “controlled” dosing.

[0073] In one embodiment as shown in Figure 7, the canister may be of the same dimensions as for a prior art (typically 10-22ml). Preferably it is filled to at least 60%, through 70%, 80% to 90% of more of its volume.

[0074] Thus, an exemplary drug for use in a modified pMDI inhaler of the invention is Salbutamol. Salbutamol is a drug used for asthma treatment. Thus, a prior art device may contain the drug and propellant in a cansiter with an internal volume of 20 ml, which is sufficient to administer up to 100-200 metered doses of medication.

[0075] Surprisingly, the Applicants have determined that a similarly-dimensioned canister using an activated carbon absorbant, and compressed to -2-10 bar with CO2 as the propellant gas, may also be used to dispense a very significant number of doses of powder from a pierced capsule. Thus, the dimensions, familiar shape, and portability of existing asthma inhalers may be potentially carried over to a similar design, but using a zero GWP propellant.

[0076] Note that although a standard metering valve is shown in the embodiment in Figure 7, such a metering valve may not be required with the Applicant’s invention. For this embodiment all that is required is to pass a sufficient minimum volume of gas to dispense the e.g. salbutamol from e.g. a pierced capsule to dispense a repeatable dose of the drug, and such minimum gas volume may not be require to be precisely metered. The minimum gas volume varies depending on the mass of powder on the exemplary capsule. For capsules containing up to 10 mg of powder, the Applicant have found such minimum gas volume may be in the range of 1-10 ml of gas (at atmospheric pressure).

[0077] Furthermore, the Applicants have determined that a number of alternative aerial gases may be used as illustrated by the data in Figure 8.

[0078] Furthermore, as noted from Figure 9 where a canister contains a compressed gas only (black rectangles), the canister must be compressed to a very high initial pressure of 16 bars in order to have a sufficient final working pressure of 8 bars at the end of its life . This pressure is too high for an existing low-cost aluminium deep-drawn canister used in an inhaler. As a result a much more expensive and bulky thick-walled CO2 cartridge would need to be used to allow 16 bars to be stored. Such cartidges are too expensive and heavy for a portable and disposable inhaler. However in the case of an activated carbon canister (black diamonds), an initial pressure of up to 10 bars could be used, which is suitable for a low-cost aluminium deep drawn canister.

[0079] Additionally, as noted from Fig 9, for the compressed gas only case, the pressure drops in half from the beginning to the end of the canister life. This would cause a substantial variation in entrainment air flow and therefore affect dose repeatability over the life of the canister. This problem is resolved by the activated carbon canister where the pressure drop is only 20% over the life of the canister.

[0080] Consequently, the embodiment shown in Figure 7 solves many problems associated with each of the different various prior art inhalers, particularly in relation to the pressing problem of high carbon footprint.

[0081] Each of Figs 2 to 6 are included to provide context to how the invention illustrated with reference to Fig 7 (and further supported by Figs 8 and 9) may be applied to modify these alternative prior art devices.

[0082] Thus, refering to Fig 2, a prior art pressurised metered dose inhaler (200) is a combination product (210) comprising a device (220), a drug (230) and a power source (240) or propellant (241). The drug (230) and propellant (241) -a liquid, typically a hydrofluroalane (HFA), are retained together in a sealed canister (245) under pressure (P). The device (220) has a body (222), a first opening (224) that receives the canister (245), and a second opening (226) out of which the aerosolised (260) drug (230) exits the device (220). The device (220) has a metering mechanism for delivering a metered dose comprising a metering valve and actuator (252), actuator seat (256) and actuator nozzle (258).

[0083] Actuation of the device results in the delivery of a metered dose, the liquid propellant expanding and aerosolising the drug which is dispensed through an appropriate adapter (90) (nasal (92) or mouthpiece (94)).

[0084] In contrast to such a prior art device, and as illustrated in fig 7, instead of a liquid propellant the device is powered by the release of an aerial gas from an adsorbent from a canister which delivers a unit dose of drug which is housed separate of the propellant.

[0085] By controlling the volume (V), and flow rate (Q) of release of the gas a unit dose of a drug can be delivered.

[0086] The drug can take the form of a powder, suspension, dispersion or emulsion, or solution.

[0087] Similarly, refering to Fig 3, a prior art dry powder inhaler (300) is a combination product (310) comprising a device (320), a drug (330) and a power source (340) such as a mechanical spring (342). The drug (330) is stored in a bulk chamber (380) which is delivered to a metering chamber (382). The device (320) has a body (322). An overcap (324) at one end houses the power source (340) and the drug (330) is fed from the bulk chamber (380) into a metering chamber (382) of a drug metering mechanism (350). Channels (326) in the device ensure that when a user inhales, air is drawn across the device and aerosolised (360) drug (330) exits the device (320).

[0088] Such a device can be modified by way of the invention such that a unit dose of a powdered drug (330) is released from a chamber actively (as opposed to passively) using an aerial gas dispensed from a power souce (40) as illustrated in Fig 7.

[0089] Similarly, refering to Fig 4, a prior art active dry powder inhaler (400) is a combination product (410) comprising a device (420), a drug (435) and a power source (440) in the form of a pump (442) and integral air reservoir (444). The drug (435) is stored in a chamber (480) in a unit dose form such as a blister (434) and is released from the chamber by a blister piercing mechanism (470) The device (420) has a body (422), a first opening (424) which receives the pump (442), and a second opening (426) out of which the aerosolised (460) drug (430) exits the device (420).

[0090] Such a device can be modified by way of the invention such that a unit dose of a powdered drug (430) is released from a chamber actively (as opposed to passively) using an aerial gas dispensed from a power source (40) as exemplified in Fig 7 which replaces the pump and integral air resevoir.

[0091] Similarly, refering to Fig 5, a prior art active soft mist inhaler (500) is a combination product (510) comprising a device (520), a drug (530) and a power source (540) in the form of a spring (542) which drives a unit dose of drug (530) from a chamber (580) through a uniblock (528) where it is aerosolised (560).

[0092] The device (520) has a body (522), a first end (524) which houses the spring (542) and a second opening (526) out of which the aerosolised (560) drug (530) exits the device (520), the dose being held in a chamber (580) intermediate the two with the uniblock (528) positioned beyond the dosing chamber.

[0093] The uniblock (528) comprises a nozzle outlet (5281), filter structure (5282), silicon wafer (5283) and glass (5284).

[0094] Such a device can be modified by way of the invention such that a unit dose of a powdered drug (530) is released from its chamber actively using an aerial gas dispensed from a power souce (40) as exemplified in Fig 7 which replaces the spring (542).

[0095] It may be further possible to replace the monolithically-fabricated uniblock with a cheaper nozzle alternative as a longer dose delivery time (t) (comparable to this method of delivery) may be achieved by controlling the timed release of the aerial gas from the dispenser. This may also result in less pressure being required through the nozzle to generate the soft mist.

[0096] Finally, referring to Fig 6 a representative prior art neubuliser (600) comprises a device (620), a drug (630) and a power source (640) - pressurised gas from a compressor (electric). The drug (630) is stored in a resevoir (680) and is aerosolised. The device (620) has a body (622). The device (620) has a body (622), an air inlet (624) and an air outlet (626) or mouthpiece out of which the aerosolised (660) drug (630) exits the device (620). The device further comprises a baffle arrangement (626) to assist aerosolization and break up.

[0097] In use the pressurised gas (air) aerosolises the liquid medication in the reservoir and as ambient air is drawn across the device to the mouthpiece it entrains aerosolided particles which are delivered to the user. Some drug loss occurs through the inlet.

[0098] Such a device can be modified by way of the invention such that the drug (630) is caused to arosolise using an aerial gas dispensed from a power source (40) as exemplified in Fig 7 as opposed to air driven electrically through a compressor. Thus, it does not require mains electric or batteries for operation. CLAUSES 1. A device (20) for delivering a drug (30) to a user via the nasal or pulmonary route wherein the device (20) uses a propellant energy source (40) to deliver the drug (30), which propellant energy source (40) is or comprises an aerial gas (41) that is stored in a canister (45), at a pressure of at least 2 Bar, adsorbed on an adsorbant (42) where it is released therefrom to dispense the drug (30), which device (20) is absent of a bag-on-valve. 2. A device as claimed in claim 1 wherein the aerial gas is air, oxygen, nitrogen, carbon dioxide . 3. A device as claimed in claim 2 wherein the aerial gas is carbon dioxide or is enriched with carbon dioxide. 4. A device as claimed in any of claims 1 to 3 which is a combination product (10) comprising the device (20) and the drug (30). 5. A device as claimed in claim 4 which further comprises a mechanism (50) for releasing a sufficient volume (V) of the aerial gas (41) at a flow rate (Q) that delivers / aerosolizes (60) a unit dose (U) of the drug (30). 6. A device as claimed in any of claims 1 to 5 further comprising a mechanism (70) for releasing the unit dose (U) of the drug (30) in a chamber (80) from which it is delivered. 7. A device as claimed in any of the preceding claims which is classed as combination product (10) wherein the drug is either: a) a dry powder (31); b) a multi-phase dispersion of a solid in a liquid (32) or a liquid in a liquid (33); or c) a single-phase solution (34). 8. A device as claimed in claim 7 wherein the device (20) is a metered dose inhaler (200) powered by the propellant energy source (40). 9. A device as claimed in claim 8 wherein the device (20) is an active metered dose inhaler. 10. A device as claimed in claim 8 comprising a mouthpiece adapter (92) or nasal adapter (94) 11. A device as claimed in claim 7 wherein the drug (30) is a) a dry powder (31) and the device (20) is a dry powder inhaler (300) powered by the propellant energy source (40). 12. A device as claimed in claim 11 wherein the drug (30) is provided in a bulk chamber (82). 13. A device as claimed in claim 11 when dependent upon claim 6, wherein the drug (30) is provided in a sealed unit dosage form (35) and the mechanism (70) is a piercing mechanism (72). 14. A device as claimed in claim 13 wherein the sealed unit dosage form comprises a blister pack (36) or capsule (37). 15. A device as claimed in claim 7 which is a soft mist inhaler (400) powered by the propellant energy source (40). 16. A device as claimed in claim 7 which is a nebuliser (500) powered by the propellant energy source (40). 17. A device as claimed in any of claims 1 to 15 further comprising a frit or filter in the gas discharge portion of the canister (45). 18. A device as claimed in any of claims 1 to 16 further comprising a Valved Holding Chamber (VHC) or spacer. 19. A device as claimed in any of claims 1 to 15 further comprising a drug metering device or drug releasing device (70). 20. A device as claimed in claim 19 when dependent on claim 5 comprising both a propellant metering device (50) and a drug metering or drug releasing device (70). 21. A method for delivering a drug (30) to a user via the nasal or pulmonary route comprising administering the drug (30) from a device (20) which uses a propellant energy source (40) to deliver the drug (30), which propellant energy source (40) is 5 or comprises an aerial gas (41) that is stored in a canister (45), at a pressure of at least 2 Bar, adsorbed on an adsorbant (42) where it is released therefrom to dispense the drug (30), which device (20) is absent of a bag-on-valve.

Claims

08 04 261. A soft mist inhaler device (500) for delivering a drug (30) to a user via the nasal or pulmonary route comprising a device (520; 20) which houses a drug (435; 30) and a power source (540; 40), wherein the device (520) comprises5 • a body (522);• a first end (524) which receives the power source (540), which is a propellant energy source (40);• a second opening (526), out of which an aerosolised (560) drug (530) exits the device (520);10 • a chamber (580) intermediate the first end and second opening which holdsa unit dose (U) of the drug (30); and• a uniblock (528) or alternative nozzle, with a nozzle outlet (5281), which is positioned beyond the chamber (580)which propellant energy source (40) is or comprises an aerial gas (41) that15 is stored in a canister (45), at a pressure of at least 2 Bar, adsorbed on anadsorbant (42) where it is released therefrom to dispense the drug (30) with a dose delivery time (t) controlled by timed release of the aerial gas from the dispenser through the uniblock or nozzle to generate a soft mist..20 2. A device as claimed in claim 1 wherein the aerial gas is air, oxygen, nitrogen,carbon dioxide .

3. A device as claimed in claim 2 wherein the aerial gas is carbon dioxide or is enriched with carbon dioxide.

254. A device as claimed in any of claims 1 to 3 wherein the drug is a unit dose of a liquid.

5. A combination product (10) comprising a device (500) as claimed in any of claims 30 1 to 4 and the drug (30).

6. A device as claimed in any of claims 1 to 4 or a combination product as claimed in claim 5 which further comprises a propellant metering mechanism (50) for releasing a sufficient volume (V) of the aerial gas (41) at a flow rate (Q) that35 delivers and aerosolizes (60) the unit dose (U) of the drug (30) via the secondopening (526).04 26co7. A device or a combination product as claimed in claim 6 comprising a mouthpiece adapter (92) or nasal adapter (94)8. A device or a combination product as claimed in claim 6 further comprising a frit or 5 filter in the canister (45) to ensure any particulates generated by the adsorbent donot leave the canister with the aerial gas.

9. A device or a combination product as claimed in claim 6 further comprising a Valved Holding Chamber (VHC) or spacer.1010. A device or a combination product as claimed in claim 6 further comprising a drug metering mechanism ordrug releasing mechanism (70).

11. A device or a combination product as claimed in claim 10 comprising both a15 propellant metering device (50) and a drug metering or drug releasing device (70).IntellectualPropertyOfficeApplication GB2513534.4Search report under Section 17 of the Patents Act 1977Date search completed: 07 October 2025Claims searched: 1-11International classificationSubclass and subgroup Valid from A61M11 / 02 01 / 01 / 2006 A61M15 / 00 01 / 01 / 2006 B65D83 / 14 01 / 01 / 2025Field of searchWorldwide search of patent documents classified in the following areas of the IPC:A61M, B65DDatabases used in the preparation of this search report:SEARCH-PATENTDocuments considered to be relevantPatent literatureCategory Relevant Document of relevanceclaimsX 1 at least WO 2020 / 142206 A1 IMPEL NEUROPHARMA INC, See whole description, especially paragraphs 0043, 0045, 0050-0052, 0055 and figures 1-2 X 1 at least WO 2012 / 119153 A2 IMPEL NEUROPHARMA INC et al., See whole description, especially paragraphs 000131-000135, 000143-000146, 000157 and figures 1-5 X 1 at least KR101978554 B1 IUCF-HYU (INDUSTRY-UNIVERSITY COOPERATION FOUND HANYANG UNIVERSITY), See whole description, especially paragraphs 0034, 0041,0050, 0075 and figures 1-3 &7 Y 1 at least WO 2014 / 070463 A1 CALGON CARBON CORP, See figure 8 and paragraphs 0018, 0021,0029 &0047 Y 1 at least US 2006 / 049215 A1 LIM &KRAUSE, See paragraphs 36, 64, and 69, and figures 1 and 5 Y 1 at least US 4049158 A JOHNSON &SON INC S C, See col.2, ln.44 - col.3, ln.27; col.7, ln.18-65 and figures 6-7Categories Letter or symbol Description X Document indicating lack of novelty or inventive step. Y Document indicating lack of inventive step, if combined with another document of the same category. & Member of the same patent family. A Document indicating technological background. P Document published on or after the priority date but before the fling date of the present application.Letter or symbol Description E Earlier application published on or after the filing date of the present application.

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