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WO2025170986A1 - Dispositif d'administration de médicament - Google Patents

Dispositif d'administration de médicament

Info

Publication number
WO2025170986A1
WO2025170986A1 PCT/US2025/014566 US2025014566W WO2025170986A1 WO 2025170986 A1 WO2025170986 A1 WO 2025170986A1 US 2025014566 W US2025014566 W US 2025014566W WO 2025170986 A1 WO2025170986 A1 WO 2025170986A1
Authority
WO
WIPO (PCT)
Prior art keywords
metered dose
dose inhaler
inhaler device
spray pattern
spray
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/014566
Other languages
English (en)
Inventor
Stephen Stein
Benjamin MYATT
Phil COCKS
Paul Young
Daniel Duke
Lingzhe RAO
Hui Xin ONG
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kindeva Drug Delivery LP
Original Assignee
Kindeva Drug Delivery LP
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kindeva Drug Delivery LP filed Critical Kindeva Drug Delivery LP
Publication of WO2025170986A1 publication Critical patent/WO2025170986A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2209/00—Ancillary equipment
    • A61M2209/02—Equipment for testing the apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D83/00—Containers or packages with special means for dispensing contents
    • B65D83/14—Containers for dispensing liquid or semi-liquid contents by internal gaseous pressure, i.e. aerosol containers comprising propellant
    • B65D83/28—Nozzles, nozzle fittings or accessories specially adapted therefor

Definitions

  • the present disclosure is generally related to a drug delivery device. More particularly, the present disclosure is related to a pressurized metered dose inhaler device, (“MDI”) that uses one or more low global warming potential (“low-GWP”) propellants.
  • MDI pressurized metered dose inhaler device
  • low-GWP low global warming potential
  • MDIs may be used, for example, to treat subjects suffering from asthma, chronic obstructive pulmonary disorder (“COPD”), bronchitis, etc.
  • COPD chronic obstructive pulmonary disorder
  • Various implementations incorporating low-GWP propellants may benefit from increased shelf life and product performance resulting, for example, from optimized propellant and solvent, and excipient combinations, while also reducing the amount of greenhouse gases in comparison to other currently used higher-GWP propellants, such as 1, 1,1,2- tetrafluoroethane (“HFA-134a,” sometimes referred to as “HFC-134a”) and 1, 1,1, 2, 3,3,3- heptafluoropropane (“HFA-227,” sometimes referred to as “HFC-227”).
  • HFA-134a 1, 1,1,2- tetrafluoroethane
  • HFC-227 1, 1,1, 2, 3,3,3- heptafluoropropane
  • the spray orifice may define an orifice exit with an orifice exit diameter.
  • the jet length may be at least 0.8 millimeters (“mm”).
  • the metered dose inhaler device may further include a composition including a propellant including 1,1- difhioroethane (“HFA-152a”).
  • the composition may be located in a canister disposed in the substantially hollow first portion. Once the composition is ejected from the orifice exit towards the mouthpiece, the composition may define a spray pattern.
  • the spray pattern may match that of a similar metered dose inhaler device using a propellant including 1,1,1,2,3,3,3-heptafluoropropane (“HFA-227”) or 1 , 1 , 1 ,2-tetrafluoroethane (“HFA-134a”) and a jet length less than or equal to 0.8 mm.
  • a propellant including 1,1,1,2,3,3,3-heptafluoropropane (“HFA-227”) or 1 , 1 , 1 ,2-tetrafluoroethane (“HFA-134a”) and a jet length less than or equal to 0.8 mm.
  • the metered dose inhaler device may further include a composition including a propellant including trans-l,l,l,3-tetrafhioropropene (“HFO-1234ze(E)”), the composition located in a canister disposed in the substantially hollow first portion.
  • a propellant including trans-l,l,l,3-tetrafhioropropene (“HFO-1234ze(E)”
  • HFO-1234ze(E) trans-l,l,l,3-tetrafhioropropene
  • the composition may define a spray pattern.
  • the spray pattern may match that of a similar metered dose inhaler device using a propellant including 1 , 1 , 1 ,2-tetrafluoroethane (“HFA-134a”) or 1,1, 1,2, 3, 3, 3 -heptafluoropropane (“HFA-227”) and a jet length less than or equal to 0.8 mm.
  • a method of manufacturing a metered dose inhaler may include making a composition including a propellant including at least one of HFA- 152a or HFO-1234ze(E), and further including at least one of a long-acting [3- adrenoreceptor agonist (“LABA”), a short-acting P-adrenoreceptor agonist (“SABA”), a corticosteroid, a long-acting muscarinic antagonist (“LAMA”), or a combination thereof.
  • the method may further include disposing the composition into a canister for use with an actuator housing.
  • the actuator housing may include a substantially hollow first portion having a first proximal end and a first distal end.
  • Figure 2 is a schematic section side view of an example nozzle block consistent with various embodiments.
  • Aerosols including Kindeva aluminum canisters crimped with 50 microliter Bespak valves were pressure filled with placebo compositions of HFC propellants HFA-134a or HFA-227, or with low-GWP propellants HFA-152a or HFO-1234ze(E), using a Pamasol (Laboratory Plant 2016/100). Pneumatic aerosol actuation was synchronized with a high-speed imaging system.
  • Jet length variation also influences plume targeting and stability.
  • Figure 11 A illustrates spray profiles for one propellant at various jet lengths.
  • Figure 1 IB illustrates probability density functions for a spray center of mass for each of the spray profiles of Figure 11A.
  • Figure 11A shows example spray extinction contours at a 15% extinction threshold for HFC propellant HFA-134a with jet lengths of 0.6, 0.8, and 1 mm. Reduced jet length leads to increased targeting angles.
  • Figure 1 IB shows how this shifts the spray’s optical center of mass (“CoM”), which is defined as the geometric center of the plume in the images and can be used to assess targeting and stability.
  • CoM changes with jet length are hypothesized to be due to nonuniform flow in the expansion chamber; longer orifices straighten the flow, have less variation in CoM, and thus have less targeting variation.
  • HFA-152a with a 0.30 mm orifice exit diameter and a 0.65 mm jet length was evaluated to match the performance of the HFA-227 reference described above, but using HFA-152a as the propellant.
  • the HFA-152a configurations with 0.30 mm orifice exit diameter resulted in a good aerodynamic particle size distribution (APSD) match with reference MDls with an HFA-227 propellant.
  • the match between HFA-227 with 0.38 mm orifice exit diameter and HFA-152a with a 0.30 mm orifice exit diameter may advantageously provide a matched APSD.
  • Filled canisters from the HFA-227 reference device were paired with actuators having a 0.30 mm orifice exit diameter and a 0.65 mm jet length and were tested to provide for completeness of analysis. This configuration had a spray pattern area that was less than the HFA-152a configuration tested with a 0.30 mm orifice exit diameter and a 0.65 mm jet length.
  • test devices that used HFA-152a as the propellant and actuators with jet lengths of at least 0.8 mm more closely matched the spray pattern from the HFA-227 MDI configuration consisting of filled canisters from the reference device that were paired with actuators with a 0.30 mm orifice diameter and a 0.65 mm jet length.
  • the spray pattern area decreased for each HFA-152a configuration using the 0.30 mm orifice diameter.
  • test device using HFA-152a and a jet length of 0.80 mm with an orifice exit diameter of 0.30 matched with the reference device using HFA-227 (with 0.38 mm orifice exit diameter).
  • a jet length between 0.8 mm and 1.5 mm may be advantageous.
  • the composition in the canister 40 may include HFA-152a low-GWP propellant.
  • the resultant spray pattern of the ejected composition from the orifice exit 49 may match that of a similar MDI using an HFA-227 propellant and a jet length of less than or equal to 0.8 mm.
  • Alternative embodiments to each of the above matched embodiments may include a jet length 46 of at least 1 mm, 1.1mm, 1.2 mm, 1.5 mm, etc., up to and including 2 mm.
  • the spray pattern of one MDI can be considered to match that of another MDI if the geometric mean of one product (Test) divided by the geometric mean of the other product (Reference) is between 0.90 and 1.11 at one or more distances for at least one of the area and ovality (if a laser-based spray pattern measurement technique is used) or for at least one of the Dmax and ovality (if an impaction-based spray pattern measurement technique is used).
  • Test geometric mean of one product
  • Reference a 1.5 mm jet length
  • the geometric means divided as described may result in between 0.90 and 1.11 at 3 cm from the distal end 25c.
  • Matching the spray pattern may be further alternatively or additionally defined as: a spray pattern Dmin that is less than or equal to a 5% deviation of the Dmin of the similar metered dose inhaler device, and a Dmax that is less than or equal to a 5% deviation of the Dmax of the similar metered dose inhaler device.
  • the jet length of the MDIs using the low-GWP propellants as described in each of the above matched embodiments may be at least 1.25 times the jet length of the similar MDI using the currently used higher-GWP HFC propellants.
  • the jet length of the MDIs using the low-GWP propellants as described in each of the above matched embodiments may be at least 1.2 times, 1.3 times, 1.4 times, 1.5 times, 2 times, 3 times, etc., the jet length of the similar MDI using the HFC propellants.
  • Such relative jet lengths may advantageously provide an optimized spray pattern match.
  • the orifice diameter 47 at the orifice exit 49 of the MDIs using the low-GWP propellants as described in each of the above matched embodiments may be no more than 0.90 times the orifice diameter 47 at the orifice exit 49 of the similar MDI using the higher-GWP HFC propellants.
  • the orifice diameter 47 at the orifice exit 49 of the MDIs using the low-GWP propellants as described in each of the above matched embodiments may be no more than 0.85, 0.80, 0.75, 0.60, 0.50, 0.40, 0.30, 0.20, 0.10, etc., times the orifice diameter 47 at the orifice exit 49 of the similar MDI using the higher-GWP HFC propellants.
  • Such relative orifice diameters 47 at the orifice exits 49 may advantageously provide an optimized aerodynamic particle size distribution (APSD) match while simultaneously providing an optimized spray pattern match.
  • APSD aerodynamic particle size distribution
  • the composition may be optimized in tandem with the MDI device hardware (e.g., jet length, orifice diameter at the orifice exit) to optimize the spray pattern for medicament deposition in the subject or user.
  • the composition may be selected such that the spray pattern for medicament deposition is similar to an MDI product that uses HFA-227 or HFA-134a as propellant(s).
  • the LABA may include formoterol, salmeterol, indacaterol, vilanterol or a pharmaceutically acceptable salt or solvate thereof, or a combination thereof.
  • the corticosteroid may include budesonide, ciclesonide, flunisolide, beclomethasone, fluticasone, mometasone or a pharmaceutically acceptable salt or solvate thereof, or a combination thereof.
  • the SAMA or LAMA may include umeclidinium, aclidinium, glycopyrrolate, ipratropium, tiotropium, or an acceptable salt or solvate thereof.
  • the composition may include budesonide and formoterol fumarate.
  • the composition may include mometasone furoate.
  • the composition may include formoterol fumarate.
  • the type and amount of medicament included in a composition may alter the spray pattern of the composition. Accordingly, the amount of medicament included in a composition may be selected to achieve a therapeutic delivered dose which can impact the spray pattern.
  • the amount of a medicament included in a composition may be expressed as a concentration of medicament in the composition (e.g., the concentration of medicament in the propellant and any excipients) by weight percentage, the weight of medicament in a given volume of the composition, or the amount of medicament delivered by a drug delivery device with set physical parameters.
  • a composition includes at least 3.5 micrograms (“ug”)/actuation (“act”), 4.0 ug/act, 4.5 ug/act, at least 5.0 ug/act, at least 5.5 ug/act, at least 6.0 ug/act, at least 10 ug/act, at least 25 ug/act, at least 50 ug/act, at least 75 ug/act, at least 100 ug/act, at least 125 ug/act, at least 150 ug/act, at least 160 ug/act, or at least 175 ug/act of medicament.
  • ug micrograms
  • act 4.0 ug/act
  • 4.5 ug/act at least 5.0 ug/act, at least 5.5 ug/act, at least 6.0 ug/act, at least 10 ug/act, at least 25 ug/act, at least 50 ug/act, at least 75 ug/act, at least 100 ug/
  • the composition includes at most 200 ug/act, at most 150 ug/act, 100 ug/act, 75 ug/act, 50 ug/act, or 10 ug/act of medicament. Depending on the medicament used, a different amount may provide a desirable pharmaceutical dose.
  • the composition may include from 3 ug/act to 10 ug/act of medicament.
  • the composition may include 150 ug/act to 180 ug of medicament.
  • the optimized MDI may deliver about 4.5 micrograms ( “ug”) of formoterol fumarate dihydrate (a medicament) and about 80 ug of budesonide (another medicament) per actuation. [0095] In another embodiment, the optimized MDI may deliver about 4.5 ug of formoterol fumarate dihydrate and about 160 ug of budesonide per actuation.
  • the optimized MDI may deliver about 4.5 ug of formoterol fumarate dihydrate and about 320 ug of budesonide per actuation.
  • the optimized MDI may deliver about 5 ug of formoterol fumarate dihydrate and about 50 ug of mometasone furoate (another medicament) per actuation.
  • the optimized MDI may deliver about 5 ug of formoterol fumarate dihydrate and about 100 ug of mometasone furoate per actuation.
  • the optimized MDI may deliver about 5 ug of formoterol fumarate dihydrate and about 200 ug of mometasone furoate per actuation.
  • the optimized MDI may deliver about 50 ug of mometasone furoate per actuation.
  • the optimized MDI may deliver about 100 ug of mometasone furoate per actuation.
  • the optimized MDI may deliver about 200 ug of mometasone furoate per actuation.
  • the composition may include one or more excipients.
  • Excipients may advantageously serve as the vehicle for a medicament or other active substance.
  • the one or more excipients may include water, poly(ethylene) glycol (“PEG”), polyvinylpyrrolidone (“povidone,” “PVP”), or a combination thereof.
  • PEG may advantageously enhance stability of the composition, enhance solubility of the medicament, or improve delivery to a subject, for example.
  • no more than 1% by weight (based on the total weight of the composition) water or PEG would be used as an excipient in a composition of the present disclosure.
  • a composition includes at least 0.03 %, at least 0.04 %, 0.05 %, at least 0.1 %, at least 0.15 %, at least 0.2 %, at least 0.25 %, or at least 0.3 % PEG by weight. In one or more embodiments, a composition includes at most 0.5 %, at most 0.45 %, at most 0.4 %, or at most 0.35 % PEG by weight.
  • the PEG may include PEG-1000, PEG-300, PEG-200, PEG-500, any PEG between PEG-100 and PEG-6000, etc.
  • a composition includes PEG-1000, PEG-300, or both PEG-1000 and PEG-300.
  • the one or more excipients may include PVP.
  • PVP may be included to enhance stability of the composition, enhance solubility of the medicament, or improve delivery to a subject, for example.
  • the form of PVP included in a composition may be selected to provide a desirable particle size.
  • a composition may include PVP K25 or PVP K30.
  • a composition includes less than or equal to 0.01 %, 0.002 %, 0.001 %, 0.0005 %, etc. of PVP by weight.
  • a composition may include oleic acid.
  • a composition includes less than or equal to 0.10%, 0.05 %, 0.01 %, 0.005 %, 0.002 %, 0.001 %, etc. of oleic acid by weight.
  • a cosolvent is included.
  • One particularly useful cosolvent is ethanol.
  • ethanol is used as a cosolvent in solution compositions, i.e., where the medicament is dissolved in the composition.
  • the ethanol may aid in dissolving the medicament whereas the medicament may not be soluble in the composition in the absence of ethanol.
  • ethanol is used as a cosolvent in suspension formulations, i.e., where the medicament is suspended in the composition.
  • the ethanol may aid in minimizing deposition of suspended medicament on the canister and valve surfaces.
  • the composition may include greater than or equal to 0.5 % ethanol and less than or equal to 15 % ethanol.
  • ethanol When used in solution compositions, ethanol may be in amounts on a weight percent basis of the total composition of at least 0.5 %, at least 1 %, at least 2 %, at least 5 %, at least 10 %, at least 15 %. When used in solution compositions, ethanol may be in amounts on a weight percent basis of the total composition of up to 20 % or up to 15 %. In certain embodiments, when used in solution compositions, ethanol may be in amounts on a weight percent basis of the total composition of between 0.5 % and 20 %, between 1 % and 20 %, between 2 % and 20 %, between 2 % and 15 %, between 5 % and 15 %, between 10 % and 15 %, or between 15 % and 20 %. In some embodiments, the ethanol content is greater than 1 7%, or at least 17.5 %, on a weight percent basis of the total composition.
  • compositions may include a propellant that is substantially or entirely pure, meaning that there is only one propellant in the composition.
  • the propellant may include a substantial percentage of HFA-152a.
  • the propellant include at least 70 % by weight HFA-152a.
  • the propellant includes at least 90 %, at least 95 %, at least 99%, or 100 % by weight HFA-152a.
  • the propellant includes a substantial percentage of HFO-1234ze(E).
  • the propellant includes at least 70 % by weight HFO-1234ze(E).
  • the propellant includes HFA-152a and does not include an impactful amount of any other propellant. In one or more embodiments, the propellant includes at least 90 %, at least 95 %, at least 99 %, or 100 % by weight of HFO-1234ze(E). In one or more embodiments, the propellant includes HFO-1234ze(E) and does not include an impactful amount of any other propellant. In one or more embodiments using HFA-152a, HFO-1234ze(E), or a combination thereof, the spray pattern may define a width that is at least 2.5 mm and less than or equal to 3 mm, at a distance of 10 mm from the second distal end 25c of the actuator housing 10.
  • a method 100 of manufacturing an MDI as described herein may include: making a composition including a propellant having at least one of HFA-152a or HFO-1234ze(E), and further including at least one of: a LABA, a SABA, a corticosteroid, a long-acting muscarinic antagonist (“LAMA”), or a combination thereof. Making such a composition is illustrated at box 110.
  • the method 100 may further include disposing the composition into the canister 40 for use with the actuator housing 10 as described herein. Disposing the composition into the canister 40 is illustrated at box 120. Disposing the composition into the canister 40 may be performed before or after crimping a valve onto the canister 40. Once the composition is disposed in the canister 40, the canister may be disposed into an actuator housing such as the actuator housings described herein.
  • a metered dose inhaler device comprising: an actuator housing comprising: a substantially hollow first portion comprising a nozzle block; a spray orifice formed in the nozzle block and operable for dispensing a spray of metered fluid; and a substantially hollow second portion defining a mouthpiece and located adjacent the substantially hollow first portion, such that the mouthpiece is configured to be placed within a mouth of a user, wherein the spray orifice defines a jet length along an orifice axis, and wherein the spray orifice defines an orifice exit with an orifice exit diameter, wherein the jet length is at least 0.8 millimeters (“mm”); and a composition comprising a propellant including 1 ,1 -difluoroethane (“HFA-152a”), the composition located in a canister disposed in the substantially hollow first portion, wherein, once the composition is ejected from the orifice exit towards the mouthpiece, the composition defines a spray pattern, and wherein the spray pattern matches that
  • Aspect 2 The metered dose inhaler device of aspect 1, wherein matching the spray pattern and the spray pattern of the similar metered dose inhaler device using a propellant comprising HFA-227 or HFA-134a and a jet length less than or equal to 0.8 mm is defined as: a result of dividing a geometric mean of the spray pattern of the metered dose inhaler device by a similar geometric mean of the spray pattern of the similar metered dose inhaler device, wherein the result is between 0.90 and 1.11 at one or more distances between 3 cm and 7 cm from a distal end of the mouthpiece.
  • Aspect 3 The metered dose inhaler device of aspect 2, wherein the geometric mean of the spray pattern comprises one or more of: a maximum dimension (“Dmax”) of the spray pattern, an area of the spray pattern, and an ovality ratio (the ratio of Dmax divided by a minimum dimension of the spray pattern (“Dmin”)).
  • Dmax maximum dimension
  • Dmin ovality ratio
  • Aspect 4 The metered dose inhaler device of any of aspects 1-3, wherein a matched spray pattern is produced when the metered dose inhaler device and the similar metered dose inhaler contain a same medicament, and a target delivered dose of each medicament is the same based on a product labelling.
  • Aspect 5. The metered dose inhaler device of any of aspects 1-4, wherein the jet length is less than or equal to 2 mm.
  • Aspect 6 The metered dose inhaler device of any of aspects 1-5, wherein the orifice exit diameter is greater than or equal to 0.2 mm and less than or equal to 0.5 mm.
  • Aspect 7 The metered dose inhaler device of any of aspects 1-6, wherein the jet length is at least 1.25 times the jet length of the similar metered dose inhaler device.
  • Aspect 8 The metered dose inhaler device of any of aspects 1-7, wherein the orifice exit diameter is not more than 0.90 times the orifice exit diameter of the similar metered dose inhaler device.
  • Aspect 9 The metered dose inhaler device of any of aspects 1-8, wherein the jet length is greater than or equal to 1 mm.
  • a method of modulating the spray pattern of the metered dose inhaler device of any of aspects 1-9, wherein modulating the spray pattern to become relatively smaller comprises adjusting the jet length to become relatively longer.
  • Aspect 11 The metered dose inhaler device of any of aspects 1-10, wherein the composition further comprises a medicament comprising at least one of a long-acting P-adrenoreceptor agonist (“LABA”), a short-acting P-adrenoreceptor agonist (“SABA”), a corticosteroid, a long-acting muscarinic antagonist (“LAMA”), or a combination thereof.
  • LAA long-acting P-adrenoreceptor agonist
  • SABA short-acting P-adrenoreceptor agonist
  • LAMA long-acting muscarinic antagonist
  • Aspect 12 The metered dose inhaler device of aspect 11, wherein the SABA comprises salbutamol, levalbuterol, terbutaline, or a pharmaceutically acceptable salt or solvate thereof, and wherein the LABA comprises formoterol, salmeterol, indacaterol, vilanterol, or a pharmaceutically acceptable salt or solvate thereof, and wherein the corticosteroid comprises budesonide, ciclesonide, flunisolide, beclomethasone, fluticasone, mometasone or a pharmaceutically acceptable salt or solvate thereof, or a combination thereof.
  • the SABA comprises salbutamol, levalbuterol, terbutaline, or a pharmaceutically acceptable salt or solvate thereof
  • the LABA comprises formoterol, salmeterol, indacaterol, vilanterol, or a pharmaceutically acceptable salt or solvate thereof
  • the corticosteroid comprises budesonide, ciclesonide, flunisolide,
  • Aspect 13 The metered dose inhaler device of aspect 11, wherein the composition comprises budesonide and formoterol fumarate.
  • Aspect 14 The metered dose inhaler device of aspect 1 1, wherein the composition comprises mometasone furoate and formoterol fumarate.
  • Aspect 15 The metered dose inhaler device of any of aspects 13-14, wherein the formoterol fumarate is in the form of formoterol fumarate dihydrate.
  • Aspect 16 The metered dose inhaler device of any of aspects 1- 11, wherein the propellant comprises at least 70 % by weight HFA-152a.
  • Aspect 18 The metered dose inhaler device of any of aspects 1-11, wherein the composition comprises ethanol.
  • Aspect 19 The metered dose inhaler device of aspect 18, wherein the composition comprises greater than or equal to 0.5 % ethanol and less than or equal to 15 % ethanol.
  • Aspect 20 The metered dose inhaler device of aspect 17, wherein the one or more excipients comprise one or more of poly(ethylene) glycol (“PEG”) or oleic acid.
  • PEG poly(ethylene) glycol
  • Aspect 23 The metered dose inhaler device of aspect 22, wherein the geometric mean of the spray pattern comprises one or more of: a maximum dimension (“Dmax”) of the spray pattern, an area of the spray pattern, and an ovality ratio (the ratio of Dmax divided by a minimum dimension of the spray pattern (“Dmin”)).
  • Dmax maximum dimension
  • Dmin ovality ratio
  • Aspect 24 The metered dose inhaler device of any of aspects 21-23, wherein a matched spray pattern is produced when the metered dose inhaler device and the similar metered dose inhaler contain a same medicament, and a target delivered dose of each medicament is the same based on a product labelling.
  • Aspect 25 The metered dose inhaler device of any of aspects 21-24, wherein the jet length is less than or equal to 2 mm.
  • Aspect 26 The metered dose inhaler device of any of aspects 21-25, wherein the orifice exit diameter is greater than or equal to 0.2 mm and less than or equal to 0.5 mm.
  • Aspect 27 The metered dose inhaler device of any of aspects 21-26, wherein the jet length is at least 1.25 times the jet length of the similar metered dose inhaler device.
  • a method of modulating the spray pattern of the metered dose inhaler device of any of aspects 21-29, wherein modulating the spray pattern to become relatively smaller comprises adjusting the jet length to become relatively longer.
  • Aspect 32 The metered dose inhaler device of aspect 31, wherein the SABA comprises salbutamol, levalbuterol, terbutaline, or a pharmaceutically acceptable salt or solvate thereof, and wherein the LABA comprises formoterol, salmeterol, indacaterol, vilanterol, or a pharmaceutically acceptable salt or solvate thereof and wherein the corticosteroid comprises budesonide, ciclesonide, flunisolide, beclomethasone, fluticasone, mometasone or a pharmaceutically acceptable salt or solvate thereof, or a combination thereof.
  • the SABA comprises salbutamol, levalbuterol, terbutaline, or a pharmaceutically acceptable salt or solvate thereof
  • the LABA comprises formoterol, salmeterol, indacaterol, vilanterol, or a pharmaceutically acceptable salt or solvate thereof
  • the corticosteroid comprises budesonide, ciclesonide, flunisolide, be
  • Aspect 33 The metered dose inhaler device of aspect 31, wherein the composition comprises budesonide and formoterol fumarate.
  • Aspect 34 The metered dose inhaler device of aspect 31, wherein the composition comprises mometasone furoate and formoterol fumarate.
  • Aspect 35 The metered dose inhaler device of any of aspects 33-34, wherein the formoterol fumarate is in the form of formoterol fumarate dihydrate.
  • Aspect 37 The metered dose inhaler device of any of aspects 20- 31, wherein the composition comprises one or more excipients.
  • Aspect 40 The metered dose inhaler device of aspect 37, wherein the one or more excipients comprise one or more of poly(ethylene) glycol (“PEG”) or oleic acid.
  • PEG poly(ethylene) glycol
  • Aspect 42 The method of aspect 41, wherein the jet length is less than or equal to 2 mm.
  • Aspect 43 The method of any of aspects 41-42, wherein the orifice exit diameter is greater than or equal to 0.2 mm and less than or equal to 0.5 mm.
  • Aspect 44 The method of any of aspects 41-43, wherein the jet length is greater than or equal to 1 mm.
  • a method of modulating a spray pattern of the metered dose inhaler of any of aspects 41-44, wherein modulating the spray pattern to become relatively smaller comprises adjusting the jet length to become relatively longer.
  • Aspect 49 The method of any of aspects 47-48, wherein the formoterol fumarate is in the form of formoterol fumarate dihydrate.
  • Aspect 52 The method of any of aspects 41-49, wherein the composition comprises one or more excipients.
  • Aspect 53 The method of any of aspects 41-49, wherein the composition comprises ethanol.
  • a metered dose inhaler device comprising: an actuator housing comprising: a substantially hollow first portion having a first proximal end and a first distal end; a base portion formed at the first proximal end, the base portion having a base plane; a nozzle block formed in the base portion; a spray orifice formed in the nozzle block and operable for dispensing a spray of metered fluid; and a substantially hollow second portion having a second proximal end and a second distal end and defining a mouthpiece, the second proximal end being located adjacent the first proximal end and the second distal end defining an end of the mouthpiece, the substantially hollow second portion defining a roof section and a floor section each extending from the second proximal end to the second distal end of the mouthpiece, wherein the mouthpiece extends away from the second proximal end such that the second distal end of the mouthpiece is configured to be placed within a mouth of a user, wherein the spray
  • Aspect 57 The metered dose inhaler device of aspect 56, wherein the jet length is less than or equal to 2 mm.
  • Aspect 58 The metered dose inhaler device of any of aspects 56-57, wherein the orifice exit diameter is greater than or equal to 0.2 mm and less than or equal to 0.5 mm.
  • Aspect 59 The metered dose inhaler device of any of aspects 56-58, wherein the jet length is greater than or equal to 1 mm.
  • a method of modulating the spray pattern of the metered dose inhaler device of any of aspects 56-59, wherein modulating the spray pattern to become relatively smaller comprises adjusting the jet length to become relatively longer.
  • Aspect 61 The metered dose inhaler device of any of aspects 56-60, wherein the composition further comprises at least one of a long-acting [3-adrenoreceptor agonist (“LABA”), a short-acting P-adrenoreceptor agonist (“SABA”), a corticosteroid, a long- acting muscarinic antagonist (“LAMA”), or a combination thereof.
  • CLA long-acting [3-adrenoreceptor agonist
  • SABA short-acting P-adrenoreceptor agonist
  • LAMA long- acting muscarinic antagonist
  • Aspect 62 The metered dose inhaler device of aspect 61, wherein the SABA comprises salbutamol, levalbuterol, terbutaline, or a pharmaceutically acceptable salt or solvate thereof, and wherein the LABA comprises formoterol, salmeterol, indacaterol, vilanterol, or a pharmaceutically acceptable salt or solvate thereof, and wherein the corticosteroid comprises budesonide, ciclesonide, flunisolide, beclomethasone, fluticasone, mometasone or a pharmaceutically acceptable salt or solvate thereof, or a combination thereof.
  • Aspect 63 The metered dose inhaler device of aspect 61, wherein the composition comprises budesonide and formoterol fumarate.
  • Aspect 64 The metered dose inhaler device of aspect 61, wherein the composition comprises mometasone furoate and formoterol fumarate.
  • Aspect 65 The metered dose inhaler device of any of aspects 63-64, wherein the formoterol fumarate is in the form of formoterol fumarate dihydrate.
  • Aspect 66 The metered dose inhaler device of any of aspects 56-65, wherein the propellant comprises at least 70 % by weight HFA-152a.
  • Aspect 67 The metered dose inhaler device of any of aspects 56-66, wherein the propellant comprises at least 70 % by weight HFO-1234ze(E).
  • Aspect 68 The metered dose inhaler device of any of aspects 56-67, wherein the composition comprises one or more excipients.
  • Aspect 69 The metered dose inhaler device of any of aspects 56-68, wherein the composition comprises ethanol.
  • Aspect 70 The metered dose inhaler device of aspect 69, wherein the composition comprises greater than or equal to 0.5 % ethanol and less than or equal to 15 % ethanol.
  • Aspect 71 The metered dose inhaler device of aspect 68, wherein the one or more excipients comprise one or more of poly(ethylene) glycol (“PEG”) or oleic acid.
  • PEG poly(ethylene) glycol
  • the term “and/or” means one or all of the listed elements or a combination of any two or more of the listed elements; the terms “comprises,” “comprising,” and variations thereof are to be construed as open ended — i.e., additional elements or steps are optional and may or may not be present; unless otherwise specified, “a,” “an,” “the,” and “at least one” are used interchangeably and mean one or more than one; and the recitations of numerical ranges by endpoints include all numbers subsumed within that range (e g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).
  • any method disclosed herein that includes discrete steps the steps may be performed in any feasible order. And, as appropriate, any combination of two or more steps may be performed simultaneously.

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  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
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  • Heart & Thoracic Surgery (AREA)
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Abstract

L'invention concerne un dispositif inhalateur doseur comprenant un logement d'actionneur (10) avec une première partie sensiblement creuse (15) comprenant un bloc gicleur, et une seconde partie sensiblement creuse (25) définissant un embout buccal et située adjacente à la première partie sensiblement creuse. Un orifice de pulvérisation (45) est formé dans le bloc gicleur (30). L'orifice de pulvérisation (45) définit une longueur de jet (46) sur un axe d'orifice. L'orifice de pulvérisation définit une sortie d'orifice (49) ayant un diamètre de sortie d'orifice (47). La longueur de jet est d'au moins 0,8 millimètre ("mm"). Le dispositif comprend une composition comprenant un agent propulseur qui comprend du 1,1-difluoroéthane ("HFA-152a") ou trans-1, 1,1,3-tétrafluoropropène ("HFO-1234ze(E) "), la composition étant située dans une cartouche (40) disposée dans la première partie sensiblement creuse (15). Une fois la composition éjectée de la sortie d'orifice (49), la composition définit une forme de dispersion du jet. La forme de dispersion du jet correspond à celle d'un dispositif similaire utilisant un agent propulseur comprenant du 1,1,1,2,3,3,3-heptafluoropropane ("HFA-227") et une longueur de jet inférieure ou égale à 0,8 mm.
PCT/US2025/014566 2024-02-06 2025-02-05 Dispositif d'administration de médicament Pending WO2025170986A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130295023A1 (en) * 2009-11-17 2013-11-07 CIPLA Limited, Mumbai, INDA Inhalation Solutions
US20200069895A1 (en) * 2017-05-17 2020-03-05 3M Innovative Properties Company Formulation and aerosol canisters, inhalers, and the like containing the formulation
US20220257878A1 (en) * 2021-02-15 2022-08-18 Glenmark Pharmaceuticals Limited Metered dose inhalers of fluticasone or an ester thereof
US20220331237A1 (en) * 2021-03-23 2022-10-20 1232176 B.C. Ltd. Device, methods and uses for treating anaphylaxis
WO2023039101A1 (fr) * 2021-09-08 2023-03-16 Kindeva Drug Delivery L.P. Inhalateurs doseurs et compositions de solution
US20230347080A1 (en) * 2020-01-28 2023-11-02 Chiesi Farmaceutici S.P.A Pressured metered dose inhalers comprising a buffered pharmaceutical formulation

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130295023A1 (en) * 2009-11-17 2013-11-07 CIPLA Limited, Mumbai, INDA Inhalation Solutions
US20200069895A1 (en) * 2017-05-17 2020-03-05 3M Innovative Properties Company Formulation and aerosol canisters, inhalers, and the like containing the formulation
US20230347080A1 (en) * 2020-01-28 2023-11-02 Chiesi Farmaceutici S.P.A Pressured metered dose inhalers comprising a buffered pharmaceutical formulation
US20220257878A1 (en) * 2021-02-15 2022-08-18 Glenmark Pharmaceuticals Limited Metered dose inhalers of fluticasone or an ester thereof
US20220331237A1 (en) * 2021-03-23 2022-10-20 1232176 B.C. Ltd. Device, methods and uses for treating anaphylaxis
WO2023039101A1 (fr) * 2021-09-08 2023-03-16 Kindeva Drug Delivery L.P. Inhalateurs doseurs et compositions de solution

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Title
BAXTER ET AL.: "AAPS PharmSciTech", vol. 23, 18 May 2022, article "Spray Pattern and Plume Geometry Testing and Methodology: An IPAC-RS Working Group Overview"
BAXTER SHERRYL ET AL: "Spray Pattern and Plume Geometry Testing and Methodology: An IPAC-RS Working Group Overview", AAPS PHARMSCITECH, SPRINGER INTERNATIONAL PUBLISHING, CHAM, vol. 23, no. 5, 18 May 2022 (2022-05-18), XP037892093, [retrieved on 20220518], DOI: 10.1208/S12249-022-02278-W *

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