GB2456028A - A medicament dispenser with an HFO propellant - Google Patents
A medicament dispenser with an HFO propellant Download PDFInfo
- Publication number
- GB2456028A GB2456028A GB0820877A GB0820877A GB2456028A GB 2456028 A GB2456028 A GB 2456028A GB 0820877 A GB0820877 A GB 0820877A GB 0820877 A GB0820877 A GB 0820877A GB 2456028 A GB2456028 A GB 2456028A
- Authority
- GB
- United Kingdom
- Prior art keywords
- valve
- dispenser package
- propellant
- medicament dispenser
- hfo
- 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.)
- Withdrawn
Links
- 239000003380 propellant Substances 0.000 title claims abstract description 47
- 239000003814 drug Substances 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 55
- 238000009472 formulation Methods 0.000 claims abstract description 41
- 239000000463 material Substances 0.000 claims abstract description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 7
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 7
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract description 7
- 229960002052 salbutamol Drugs 0.000 claims abstract description 7
- HCDGVLDPFQMKDK-UHFFFAOYSA-N hexafluoropropylene Chemical class FC(F)=C(F)C(F)(F)F HCDGVLDPFQMKDK-UHFFFAOYSA-N 0.000 claims abstract description 6
- NDMMKOCNFSTXRU-UHFFFAOYSA-N 1,1,2,3,3-pentafluoroprop-1-ene Chemical class FC(F)C(F)=C(F)F NDMMKOCNFSTXRU-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000006184 cosolvent Substances 0.000 claims abstract 2
- -1 bromo-butyl Chemical group 0.000 claims description 20
- 239000004480 active ingredient Substances 0.000 claims description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 229920002725 thermoplastic elastomer Polymers 0.000 claims description 8
- 239000004743 Polypropylene Substances 0.000 claims description 6
- 229920000728 polyester Polymers 0.000 claims description 6
- 229920000573 polyethylene Polymers 0.000 claims description 6
- 229920001155 polypropylene Polymers 0.000 claims description 6
- 229920002943 EPDM rubber Polymers 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- 229920001084 poly(chloroprene) Polymers 0.000 claims description 5
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 5
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
- CDOOAUSHHFGWSA-OWOJBTEDSA-N (e)-1,3,3,3-tetrafluoroprop-1-ene Chemical compound F\C=C\C(F)(F)F CDOOAUSHHFGWSA-OWOJBTEDSA-N 0.000 claims description 4
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 claims description 4
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- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 claims description 4
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- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 claims description 4
- DMUPYMORYHFFCT-UPHRSURJSA-N (z)-1,2,3,3,3-pentafluoroprop-1-ene Chemical compound F\C=C(/F)C(F)(F)F DMUPYMORYHFFCT-UPHRSURJSA-N 0.000 claims description 3
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- 229960001361 ipratropium bromide Drugs 0.000 claims description 3
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 claims description 3
- 229960004017 salmeterol Drugs 0.000 claims description 3
- 230000003068 static effect Effects 0.000 claims description 3
- QAERDLQYXMEHEB-UHFFFAOYSA-N 1,1,3,3,3-pentafluoroprop-1-ene Chemical compound FC(F)=CC(F)(F)F QAERDLQYXMEHEB-UHFFFAOYSA-N 0.000 claims description 2
- FXRLMCRCYDHQFW-UHFFFAOYSA-N 2,3,3,3-tetrafluoropropene Chemical compound FC(=C)C(F)(F)F FXRLMCRCYDHQFW-UHFFFAOYSA-N 0.000 claims description 2
- FDMFUZHCIRHGRG-UHFFFAOYSA-N 3,3,3-trifluoroprop-1-ene Chemical compound FC(F)(F)C=C FDMFUZHCIRHGRG-UHFFFAOYSA-N 0.000 claims description 2
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 claims description 2
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- 239000004033 plastic Substances 0.000 claims description 2
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- 229960000257 tiotropium bromide Drugs 0.000 claims description 2
- PGJHURKAWUJHLJ-UHFFFAOYSA-N 1,1,2,3-tetrafluoroprop-1-ene Chemical compound FCC(F)=C(F)F PGJHURKAWUJHLJ-UHFFFAOYSA-N 0.000 claims 1
- 230000001088 anti-asthma Effects 0.000 abstract 1
- 239000000924 antiasthmatic agent Substances 0.000 abstract 1
- 229940127225 asthma medication Drugs 0.000 abstract 1
- 229940071648 metered dose inhaler Drugs 0.000 description 13
- 230000000694 effects Effects 0.000 description 5
- 230000014759 maintenance of location Effects 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
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- 150000003839 salts Chemical class 0.000 description 4
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 3
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- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
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Classifications
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- 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
- A61M15/0065—Inhalators with dosage or measuring devices
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- 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
- B65D83/44—Valves specially adapted for the discharge of contents; Regulating devices
- B65D83/52—Metering valves; Metering devices
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C19/00—Acyclic saturated compounds containing halogen atoms
- C07C19/08—Acyclic saturated compounds containing halogen atoms containing fluorine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C21/00—Acyclic unsaturated compounds containing halogen atoms
- C07C21/02—Acyclic unsaturated compounds containing halogen atoms containing carbon-to-carbon double bonds
- C07C21/18—Acyclic unsaturated compounds containing halogen atoms containing carbon-to-carbon double bonds containing fluorine
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K3/00—Materials not provided for elsewhere
- C09K3/30—Materials not provided for elsewhere for aerosols
-
- 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
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Abstract
A medicament dispenser package comprises a dispensing container 2, a valve 3 and a medicinal formulation. The medicinal formulation comprises an HFO propellant, which propels and dispenses the medicinal formulation upon opening of the valve 3. Preferably, the HFO propellant comprises one or more of the group pentafluoropropenes, hexafluoropropenes or tetrafluoropropenes. Ethanol, or another co-solvent, may be provided with the propellant. The dispenser may dispense anti-asthma medication, e.g salbutamol. The inside of the container and valve may be coated with a siloxane -containing material or a fluorinated hydrocarbon containing material.
Description
--2456028 P103905GB IWROVZNTS IN OR RELATING TO)DICANENT DISPENSERS This invention relates to medicament dispensers for dispensing a medicinal formulation. In particular, the invention relates to new, improved propellants for use in medicament dispensers to propel the medicinal formulation from a pressurised dispensing container in which it is stored.
One type of medicament dispenser is a metered dose inhaler (MDI), which provides metered doses of medicinal formulation to a user. These dispensers are typically used to treat asthma, and are known as asthma inhalers. Various types of valve exist or are known in the art at this time and these dispensers use a metering valve in order to provide the metered doses of medicinal formulation.
Metering valves can be summarised as capillary retention valves or fast-fill, fast-empty valves. In each case an MDI * ** ... is provided by a container and a valve and contains a T.*** medicinal formulation, which is stored and sealed in the pressurised dispensing container and can be propelled from * the pressurised dispensing container by the propellant on ***.*.
* actuation of the valve. The pressurised dispensing container, valve and medicinal formulation together provide *: a medicarnent dispenser package. Examples of capillary retention valves are shown in publications US 6,095,182, GB 2401099 and GB 2340477. Each document discloses a different form of capillary retention valve which, when the valve stem is in a rest position, has a small passageway (capillary) which allows the medicinal formulation to enter a metering chamber within the valve, and remain there because of the capillary effect in that small passageway, even if the valve is inverted. A fast-fill, fast-empty P103905GB valve is shown in publications EP 0803449 and EP 0801009.
EP 0803449 relates to a typical fast-fill, fast-empty valve in which larger passageways are provided so that upon inverting the dispensing apparatus into its dispensing position, the medicinal formulation flows into the metering chamber and fills the metering chamber prior to dispensing of a metered dose. If the dispensing apparatus were to be inverted prior to dispensing a dose, the medicinal formulation would flow easily out of the channels and, thus, empty the metering chamber. EP 0801009 provides a variant on this concept in which the metering chamber is only formed once the valve stem is depressed into the container.
Therefore, this disclosure relates to a temporary metering chamber arrangement. The medicinal formulation can, again, easily flow into and out of the region of the metering chamber but, as the metering chamber is only formed once the valve stem is depressed within the dispenser, this invention does not rely upon capillary retention of medicinal .. formulation in the metering chamber.
* *._.
Those skilled in the art will know that before the late
I
* ** III * : 1980s MDIs utilised chioroflorocarbons (CFCs) as propellants * * to dispense a medicinal formulation. Owing to the impact of CFC5 on the environment, the Montreal Protocol was put in * : place to phase out the use of CFCs, which had been shown to * 25 have an effect on ozone depreciation in the atmosphere.
Around that time, a great deal of research was carried out in order to find replacements for CFCs and Hydrofluorocarbons HFCs/HFAs were considered a suitable alternative to CFCs. HFCs/HFAs have now nearly completely replaced CFCs as the propellant used in MDIs. The advantage of HFC5/HFAs over CFCs is that they are considered to have a lower potential for global warming, as the P103905GB HFCs/HFA5 are less likely to break down stratospheric ozone.
However, whilst HFCS/HFAs have less of an effect on global warming than CFCs, they do still have some effect.
There is a need, therefore, to provide alternative propellants for use in MDIs. For this technical field in particular, as a patient inhales the product from the MDI, the propellant must be non-toxic, whilst carrying out its other duties as a propellant of the medicinal formulation contained in the MDI. Owing to the number of different medicinal formulations, the propellant must also be chemically stable and not react with parts of the MDI, for example the materials which provide the container or a valve which seals the container, and the propellant must be chemically stable and not react with any of the active ingredients provided in the medicinal formulations, nor any additives to those medicinal formulations, such as ethanol, or surfactants.
Accordingly, in an aspect of the present invention, * ?P there is provided a medicament dispenser package comprising a dispensing container, a valve and a medicinal formulation, wherein the medicinal formulation comprises an HFO : propellant, which propels and dispenses the medicinal : formulation upon opening of the valve.
The HFO (hydrofluoroolefin) propellant may be provided with or without ethanol. Preferably, the HFO propellant is one or more of the group pentafluoropropene(s).
Alternatively, the HFO propellant may be one or more of the group hexafluoropropene(s). Most preferably, the HFO propellant is trans-1,3,3,3-tetrafluoropropene, as this compound has low toxicity. Mixtures of the propellants may P103905GB also be provided. As such, the HFO propellant may be selected from one or more of: trans-i, 3,3, 3-tetrafluoropropene; hexafluoropropene; 1,2,3,3, 3-pentafluoropropene (Z isomer); 1,2,3, 3,3-pentafluoropropene CE isomer); 1,1,3,3, 3-pentafluoropropene; 1,1,2,3, 3-pentafluoropropene; 2,3,3,3-tetrafluoropropene; 3,3, 3-trifluoropropene.
The valve may comprise one or more dynamic seals formed from a material comprising an elastomer, EPDM, bromo-butyl, chioro-butyl, butyl, nitrile, neoprene, and/or Vistamaxx(RTM) -polyolef in thermoplastic elastomer with isotactic propylene crystallinity, or mixtures thereof.
Further, the valve may comprise one or more static seals formed from a material comprising an elastomer, EPDM, bromo-butyl, chiorobutyl, butyl, nitrile, neoprene, and/or Vistamaxx(RTM) -polyolefin thermoplastic elastomer with isotactic propylene crystallinity, or mixtures thereof.
The seals provide a good barrier to oxygen ingress, preventing oxygen spoiling the medicinal formulation. The seal materials can be chosen specifically for their oxygen barrier effect or may be coated to provide an improved S...
oxygen barrier. Further, the seal materials are chosen for : their ability to minimise propellant/active ingredient : leaching and moisture ingress, which could spoil the medicinal formulation. S.
Additionally, the valve may comprise rigid components, I.....
* * such as a valve stem, valve body and/or metering chamber, formed from a material comprising plastics, TPEs, polyacetal (POM), polyester (PBT), co-polyester, nylon 6, nylon 66, polypropylene (PP), polythene (PE), PP/butyl blends and/or PE/butyl blends, or mixtures thereof.
P103905GB The medicinal formulation preferably further comprises an active ingredient selected from one or more of Salbutamol, Salmeterol, Flunisolide, Fluticasone, Beclomethasone, Formoterol, Budesonide, Ipratropium Bromide, Terbutaline, Fenoterol, Triamcinalone and/or Tiotropium Bromide.
The dispensing apparatus may comprise a coating of siloxane and/or fluorinated hydrocarbon on valve components and/or the container. Preferably, the inner surface of the container and/or a metering chamber of the valve is coated with a siloxane-containing material that is formed by a cold-plasma polymerisation of the siloxane. Alternatively, the inner surface of the container and/or a metering chamber of the valve is coated with a fluorinated hydrocarbon-containing material that is formed by a cold-plasma polymerisation of the fluorinated hydrocarbon.
Alternatively, the medicinal formulation may comprise an HFQ propellant and a non HFO propellant, for example the medicinal formulation may comprise a mixture of HFO and HFC/HFA as a propellant.
The propellant of the present invention can also be * S..
utilised with non-metering valves, for example continuous flow valves.
The use of HFOs, in particular HFOs from the groups hexafluoropropenes and pentafluoropropeneS, which are both inflammable HFOs, provide an MDI which can dispense a *.S...
* medicinal formulation in a very similar manner to those MDIs known in the art which are propelled by HFCs/HFAs or CFCS but has less impact on global warming than HFCs/HFAs or CFCs.
The metered dose inhaler may be for use in a pharmaceutical dispensing device, such as, for example, a P103905GB pulmonary, nasal, or sub-lingual delivery device. A preferred use of the apparatus of the present invention is in a pharmaceutical metered dose aerosol inhaler device.
The term pharmaceutical as used herein is intended to encompass any pharmaceutical, compound, composition, medicament, agent or product which can be delivered or administered to a human being or animal, for example pharmaceuticals, drugs, biological and medicinal products.
Examples include aritiallergics, analgesics, antibodies, vaccines, bronchodilators, antihistamines, therapeutic proteins and peptides, antitussives, anginal preparations, antibiotics, anti-inflammatory preparations, hormones, or sulfonamides, such as, for example, a vasoconstrictive amine, an enzyme, an alkaloid, or a steroid, including combinations of two or more thereof. In particular, examples include isoproterenol [alpha-(isopropylaminomethyl) protocatechuyl alcohol], phenylephrine, phenyipropanolamine, glucagon, insulin, DNAse, adrenochrome, trypsin, epinephrine, ephedrine, narcotine, codeine, atropine, *:,9 heparin, morphine, dihydromorphinone, ergotamine, scopolamine, methapyrilene, cyanocobalamiri, terbutaline, * .0* rimiterol, salbutamol, flunisolide, colchicine, pirbuterol, : beclomethasone, orciprenaline, fentanyl, and diamorphine, *:*" streptomycin, penicillin, procaine penicillin, tetracycline, chiorotetracycline and hydroxytetracycline, Se: adrenocorticotropic hormone and adrenocortical hormones, S.....
* such as cortisone, hydrocortisone, hydrocortisone acetate and prednisolone, insulin, cromolyn sodium, and mometasone, including combinations of two or more thereof.
The pharmaceutical may be used as either the free base or as one or more salts conventional in the art, such as, for example, acetate, benzenesulphonate, benzoate, P103905GB bicarbonate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochioride, edetate, edisylate, estolate, esylate, fumarate, fluceptate, gluconate, glutamate, glycollylarsanilate, hexyiresorcinate, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methyibromide, methylnitrate, methylsulphate, mucate, napsylate, nitrate, pamoate, (embonate), pantothenate, phosphate, diphosphate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulphate, tannate, tartrate, and triethiodide, including combinations of two or more thereof. Cationic salts may also be used, for example the alkali metals, e.g. Na and K, and animonium salts and salts of amines known in the art to be pharmaceutically acceptable, for example glycine, ethylene diamine, choline, diethanolamine, triethanolamine, octadecylamine, diethylamine, triethylamine, 1-amino-2-propanol-amino2-(hydroxymethyl)prOPafle-1,3-dio1. and 1-(3,4- *:*: dihydroxyphenyl) -2 isopropylaminoethanol.
The pharmaceutical will typically be one which is a...
suitable for inhalation and may be provided in any suitable :: form for this purpose, for example as a solution or powder : suspension in a solvent or carrier liquid, for example ethanol, or isopropyl alcohol.
: * The pharmaceutical may, for example, be one which is S.....
* suitable for the treatment of asthma. Examples include salbutamol, beclomethasone, salmeterol, fluticasone, formoterol, terbutaline, sodium chromoglycate, budesonide and flunisolide, ipratropium bromide and salbutamol, and physiologically acceptable salts (for example salbutamol sulphate, salmeterol xinafoate, fluticasone propionate, 97 9138 P103905GB beclomethasone dipropionate, and terbutaline sulphate>, solvates and esters, including combinations of two or more thereof. Individual isomers such as, for example, R-salbutamol, may also be used. As will be appreciated, the pharmaceutical may comprise of one or more active ingredients, an example of which is flutiform, and may optionally be provided together with a suitable carrier, for example a liquid carrier. One or more surfactants may be included if desired.
The seals and gaskets of the valve may be formed from any suitable material having acceptable performance characteristics. Preferred examples include nitrile, EPDM and other thermoplastic elastomers, butyl and neoprene.
Other rigid components of the valve, such as the valve body, chamber body, metering chamber and valve stem may be formed, for example, from polyester, nylon, acetal or similar. Alternative materials for the rigid components of the valve include stainless steel, ceramics and glass.
These rigid components can be termed as non-sealing *:*: components', although it will be understood that an inner *::::* seal, outer seal or gasket may form a seal when abutting the so-called non-sealing components. Further, the container * * may be formed from stainless steel, ceramics, glass, polyester, nylon, acetal and/or similar.
S
In order that the invention may now be disclosed, *5*�*S * * embodiments will be described, by way of example only, with reference to the following drawings, in which: Figure 1 is a side elevation of a medicamerit dispenser according to the present invention; and Figure 2 is a cross-sectional, side elevation of part of a medicament dispenser package according to the present P103905GB invention, including the medicament dispenser *of Figure 1 and containing a medicinal formulation.
Figure 1 shows an MDI, indicated in general by reference 1. The MDI 1 comprises a container 2 and a metering valve 3. The container 2 shown in Figure 1 has an optional deposition-reducing coating 10 on an inner surface thereof. The metering valve 3 is connected to the container 2 with a ferrule 4 and has a valve stem 5, for dispensing a medicinal formulation contained in the pressurised dispensing container 1. The novel HFO propellants of the present invention are suitable for use with a range of metering valves as mentioned above -capillary retention valves and fast-fill, fast-empty valves. Operation of those metering valves is described in more detail in publications US 6,095,182, GB 2401099, GB 2340477, EP 0803449 and EP 0801009 and the reader is directed to those publications for a fuller understanding of the operation of metering valves and MDIs in general.
In the following, and as shown in the cross-sectional view of Figure 2, the present invention will be illustrated with a valve as described in publication EP 0803449.
* The MDI 1 is shown in its inverted, dispensing * * position. The container 2 and the valve 3 store and seal a :. 25 medicinal formulation 12 in the MDI 1. * sq.
According to the present invention, the medicinal *5S*.. * S
formulation comprises an HFO propellant, which propels and dispenses the medicinal formulation upon opening of the valve. In addition to the propellant, the formulation includes one or more active ingredients (typically medicaments), optionally one or more subsidiary components such as solvents, co-solvents, etc. In one example, the -10 -P103905GB propellant is trans-1,3,3,3-tetrafluoropropene and the active ingredient is salbutamol. The propellant, trans-1,3,3,3-tetrafluoropropene, has been found to be particularly suitable for use with MDIs and other medicament dispensers as the propellant has good toxicity characteristics. Operation of the valve with this new propellant is the same, if not improved, over valve operation with HFCs/HFAs. The static seal 14 is preferably formed from a material comprising Vistamaxx(RTM) -polyolef in thermoplastic elastomer with isotactic propylene crystallinity. Vistamaxx(RTM) materials are described in detail in publications WO 2006/092618 and WO 2008/029111.
The dynamic seals 20,21 are preferably formed from a material comprising EPDM.
The propellant and active ingredient are, advantageously, chemically stable and compatible with each other and the valve materials, in particular the valve seals, gasket and valve body parts. As such, the HFO propellants of the present invention provide a good *:.::o alternative to the HFCs/HFAs propellant of known MDIs.
According to the present invention, an HFO propellant provides a good medium by which the active ingredient of the * medicinal formulation can be dispensed from the MDI. It * * will be clear to the skilled person that the HFO propellants :..25 may be used with all known types of valve useful for * medicament dispensers, whether metering valves or continuous *SS*.. * .
flow valves.
Claims (17)
- -11 -P103905GB CLAIMS: 1.) A medicament dispenser package comprising a dispensing container, a valve and a medicinal formulation, wherein the medicinal formulation comprises an HFO propellant, which propels and dispenses the medicinal formulation upon opening of the valve.
- 2.) A medicament dispenser package as claimed in claim 1, wherein the HFO propellant is provided with or without ethanol, and/or another co-solvent.
- 3.) A medicament dispenser package as claimed in claim 1 or claim 2, wherein the HFO propellant is one or more of the group pentafluoropropene(s).
- 4.) A medicament dispenser package as claimed in any preceding claim, wherein the HFO propellant is one or more of the group hexafluoropropene(s), or one or more of the group tetrafluoropropene(s). * *****. .
- 5.) A medicamerit dispenser package as claimed in any preceding claim, wherein the HFO propellant is trans-*S*S..* : 1,3,3,3-tetrafluoropropene.***..S * * :. 25
- 6.) A medicament dispenser package as claimed in any *..*.: preceding claim, wherein the HFO propellant is selected from one or more of: trans-i, 3,3, 3-tetrafluoropropene; hexafluoropropene; 1,2,3,3, 3-pentafluoropropene (Z isomer); l,2,3,3,3-pentafluoropropene CE isomer); 1,1,3,3, 3-pentafluoropropene; 1,1,2,3, 3-pentafluoropropefle; 2,3,3, 3-tetrafluoropropene; 3,3, 3-trifluoropropene.-12 -P103905GB
- 7.) A medicament dispenser package as claimed in any preceding claim, wherein the valve comprises one or more dynamic seals formed from a material comprising an elastomer, EPDM, bromo-butyl, chioro-butyl, butyl, nitrile, neoprene, and/or Vistamaxx(RTM) -polyolefin thermoplastic elastomer with isotactic propylene crystallinitY, or mixtures thereof.
- 8.) A medicament dispenser package as claimed in any preceding claim, wherein the valve comprises one or more static seals formed from a material comprising an elastomer, E P DM, bromo-butyl, chiorobutyl, butyl, nitrile, neoprene, and/or Vistamaxx(RTM) -polyolef in thermoplastic elastomer with isotactic propylene crystallinitY, or mixtures thereof.
- 9.) A medicament dispenser package as claimed in any preceding claim, wherein the valve comprises rigid * ** *.,,!0 components, such as a valve stem, valve body and/or metering *::* chamber, formed from a material comprising plastics, TPEs, polyacetal (POM), polyester (PBT), co-polyester, nylon 6, I.....* : nylon 66, polypropylene (PP), polythene (PE), PP/butyl * S I S S. * blends and/or PE/butyl blends, or mixtures thereof. *1 * * * S..:
- 10.) A medicament dispenser package as claimed in any preceding claim, wherein the medicinal formulation further comprises an active ingredient selected from one or more of Salbutamol, Salmeterol, Flunisolide, FluticasOfle, BeclomethaSOne, FormoterOl, Budesonide, Ipratropium Bromide, Terbutalifle, FenoterOl, TriamcthalOne and/or TiotropiUm Bromide.-13 -P103905GB
- 11.) A rnedicament dispenser package as claimed in any preceding claim, wherein the dispensing apparatus comprises a coating of siloxane and/or fluorinated hydrocarbon on valve components and/or the container.
- 12.) A rnedicament dispenser package as claimed in claim 11, wherein the inner surface of the container and/or a metering chamber of the valve is coated with a siloxane-containing material that is formed by a cold-plasma polymerisation of the siloxane.
- 13.) A medicament dispenser package as claimed in claim 11, wherein the inner surface of the container and/or a metering chamber of the valve is coated with a fluorinated hydrocarbon-containing material that is formed by a cold-plasma polymerisation of the fluorinated hydrocarbon.
- 14.) A medicament dispenser package as claimed in any * I. ,20 preceding claim, wherein the medicinal formulation comprises **e.an HFO propellant and a non-HFO propellant.*
- 15.) A medicament dispenser package as claimed in claim 14, S.....* wherein the medicinal formulation comprises a mixture of HFO :. 25 and HFC/HFA as a propellant. * S..S..... * .
- 16.) A medicament dispenser package substantially as herein described, with reference to the drawings and/or specificdescription.
- 17.) An HFO, medicament propellant substantially as hereindescribed, with reference to the description.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0820877A GB2456028A (en) | 2008-11-14 | 2008-11-14 | A medicament dispenser with an HFO propellant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0820877A GB2456028A (en) | 2008-11-14 | 2008-11-14 | A medicament dispenser with an HFO propellant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0820877D0 GB0820877D0 (en) | 2008-12-24 |
| GB2456028A true GB2456028A (en) | 2009-07-01 |
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ID=40194656
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0820877A Withdrawn GB2456028A (en) | 2008-11-14 | 2008-11-14 | A medicament dispenser with an HFO propellant |
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| GB (1) | GB2456028A (en) |
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| US9554982B2 (en) | 2012-09-14 | 2017-01-31 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
| US9579265B2 (en) | 2014-03-13 | 2017-02-28 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
| US9662285B2 (en) | 2014-03-13 | 2017-05-30 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
| US11083915B2 (en) | 2013-07-16 | 2021-08-10 | The Procter & Gamble Company | Antiperspirant spray devices and compositions |
| WO2021156602A1 (en) * | 2020-02-05 | 2021-08-12 | Bespak Europe Limited | Pressurised dispensing container |
| US11186424B2 (en) | 2013-07-16 | 2021-11-30 | The Procter & Gamble Company | Antiperspirant spray devices and compositions |
| WO2023039101A1 (en) * | 2021-09-08 | 2023-03-16 | Kindeva Drug Delivery L.P. | Metered dose inhalers and solution compositions |
| RU2800100C1 (en) * | 2020-02-05 | 2023-07-18 | Беспак Юроп Лимитед | Distribution container under pressure |
| WO2024181972A1 (en) * | 2022-03-01 | 2024-09-06 | Kindeva Drug Delivery L.P. | Metered dose inhalers and high-dose suspensions |
| US12383516B1 (en) * | 2025-01-06 | 2025-08-12 | Amphastar Pharmaceuticals, Inc. | Albuterol aerosol suspension formulation for oral inhalation with high amount of green propellant hydrofluoroolefin (HFO) and free of co-solvent |
| WO2025229354A1 (en) * | 2024-05-03 | 2025-11-06 | Senari Pharma Ltd | Aerosol comprising salbutamol sulfate and beclomethasone dipropionate |
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| US9554981B2 (en) | 2012-09-14 | 2017-01-31 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
| US10076489B2 (en) | 2012-09-14 | 2018-09-18 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
| US10076490B2 (en) | 2012-09-14 | 2018-09-18 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
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| US11186424B2 (en) | 2013-07-16 | 2021-11-30 | The Procter & Gamble Company | Antiperspirant spray devices and compositions |
| US11083915B2 (en) | 2013-07-16 | 2021-08-10 | The Procter & Gamble Company | Antiperspirant spray devices and compositions |
| US9579265B2 (en) | 2014-03-13 | 2017-02-28 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
| US9662285B2 (en) | 2014-03-13 | 2017-05-30 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
| US10076474B2 (en) | 2014-03-13 | 2018-09-18 | The Procter & Gamble Company | Aerosol antiperspirant compositions, products and methods |
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| CN115397747A (en) * | 2020-02-05 | 2022-11-25 | 贝斯帕克欧洲有限公司 | Pressurized dispensing container |
| US12466636B2 (en) | 2020-02-05 | 2025-11-11 | Bespak Europe Limited | Pressurised dispensing container |
| JP2023512840A (en) * | 2020-02-05 | 2023-03-29 | ベスパク ユーロップ リミテッド | Pressurized dispensing container |
| RU2800100C1 (en) * | 2020-02-05 | 2023-07-18 | Беспак Юроп Лимитед | Distribution container under pressure |
| GB2607500B (en) * | 2020-02-05 | 2023-11-29 | Bespak Europe Ltd | Pressurised dispensing container |
| JP2024052867A (en) * | 2020-02-05 | 2024-04-12 | ベスパク ユーロップ リミテッド | Pressurized Dispensing Container |
| WO2023039101A1 (en) * | 2021-09-08 | 2023-03-16 | Kindeva Drug Delivery L.P. | Metered dose inhalers and solution compositions |
| WO2023039104A1 (en) * | 2021-09-08 | 2023-03-16 | Kindeva Drug Delivery L.P. | Propellants for anticholinergic agents in pressurized metered dose inhalers |
| WO2024181972A1 (en) * | 2022-03-01 | 2024-09-06 | Kindeva Drug Delivery L.P. | Metered dose inhalers and high-dose suspensions |
| WO2025229354A1 (en) * | 2024-05-03 | 2025-11-06 | Senari Pharma Ltd | Aerosol comprising salbutamol sulfate and beclomethasone dipropionate |
| US12383516B1 (en) * | 2025-01-06 | 2025-08-12 | Amphastar Pharmaceuticals, Inc. | Albuterol aerosol suspension formulation for oral inhalation with high amount of green propellant hydrofluoroolefin (HFO) and free of co-solvent |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0820877D0 (en) | 2008-12-24 |
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| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |