GB2460843A - Cold plasma polymer coated pressurised dispensing apparatus - Google Patents
Cold plasma polymer coated pressurised dispensing apparatus Download PDFInfo
- Publication number
- GB2460843A GB2460843A GB0810614A GB0810614A GB2460843A GB 2460843 A GB2460843 A GB 2460843A GB 0810614 A GB0810614 A GB 0810614A GB 0810614 A GB0810614 A GB 0810614A GB 2460843 A GB2460843 A GB 2460843A
- Authority
- GB
- United Kingdom
- Prior art keywords
- coating
- pressurised dispensing
- layer
- valve
- fluorinated hydrocarbon
- 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- Withdrawn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
- 230000005495 cold plasma Effects 0.000 title claims abstract description 27
- 229920000642 polymer Polymers 0.000 title abstract 5
- 238000000576 coating method Methods 0.000 claims abstract description 95
- 239000000203 mixture Substances 0.000 claims abstract description 94
- 239000011248 coating agent Substances 0.000 claims abstract description 85
- 238000009472 formulation Methods 0.000 claims abstract description 57
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract description 47
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 43
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 42
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000003380 propellant Substances 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 238000006116 polymerization reaction Methods 0.000 claims description 18
- 229940126601 medicinal product Drugs 0.000 claims description 9
- 238000003860 storage Methods 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 7
- 208000006673 asthma Diseases 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 238000000151 deposition Methods 0.000 description 31
- 230000008021 deposition Effects 0.000 description 31
- 239000007789 gas Substances 0.000 description 21
- 239000000178 monomer Substances 0.000 description 14
- -1 for example Chemical class 0.000 description 12
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- 238000001228 spectrum Methods 0.000 description 9
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- 239000001301 oxygen Substances 0.000 description 8
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- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000000356 contaminant Substances 0.000 description 6
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
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- 230000003639 vasoconstrictive effect Effects 0.000 description 1
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
- A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D1/00—Processes for applying liquids or other fluent materials
- B05D1/62—Plasma-deposition of organic layers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D5/00—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
- B05D5/08—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures to obtain an anti-friction or anti-adhesive surface
- B05D5/083—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures to obtain an anti-friction or anti-adhesive surface involving the use of fluoropolymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D7/00—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials
- B05D7/22—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials to internal surfaces, e.g. of tubes
- B05D7/227—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials to internal surfaces, e.g. of tubes of containers, cans or the like
-
- 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 or packages with special means for dispensing contents for delivery of liquid or semi-liquid contents by internal gaseous pressure, i.e. aerosol containers comprising propellant for a product delivered by a propellant
-
- 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 or packages with special means for dispensing contents for delivery of liquid or semi-liquid contents by internal gaseous pressure, i.e. aerosol containers comprising propellant for a product delivered by a propellant
- B65D83/38—Details of the container body
-
- 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 or packages with special means for dispensing contents for delivery of liquid or semi-liquid contents by internal gaseous pressure, i.e. aerosol containers comprising propellant for a product delivered by a propellant
- B65D83/44—Valves specially adapted therefor; Regulating devices
- B65D83/52—Valves specially adapted therefor; Regulating devices for metering
- B65D83/54—Metering valves ; Metering valve assemblies
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F114/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen
- C08F114/18—Monomers containing fluorine
- C08F114/185—Monomers containing fluorine not covered by the groups C08F114/20 - C08F114/28
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F114/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen
- C08F114/18—Monomers containing fluorine
- C08F114/26—Tetrafluoroethene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/52—Polymerisation initiated by wave energy or particle radiation by electric discharge, e.g. voltolisation
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L27/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers
- C08L27/02—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment
- C08L27/12—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment containing fluorine atoms
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L27/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers
- C08L27/02—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment
- C08L27/12—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment containing fluorine atoms
- C08L27/18—Homopolymers or copolymers or tetrafluoroethene
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/02—Halogenated hydrocarbons
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Dispersion Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Materials Engineering (AREA)
- Mechanical Engineering (AREA)
- Animal Behavior & Ethology (AREA)
- Plasma & Fusion (AREA)
- Physics & Mathematics (AREA)
- Wood Science & Technology (AREA)
- Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
Abstract
A pressurised dispensing apparatus is characterised by a cold plasma polymer coating on one or more internal surfaces of the pressurised dispensing apparatus, wherein a medicinal formulation comprises a fluorinated hydrocarbon propellant, such as HFC134a or the isomer HFC134, HFC227a or the isomer HFC227, and the polymer coating is formed from the same compound comprising the fluorinated hydrocarbon propellant. Also disclosed is a pressurised dispensing apparatus, characterised by a cold plasma polymer coating on one or more internal surfaces of the pressurised dispensing apparatus, wherein a medicinal formulation comprises either HFC134a propellant fluorinated hydrocarbon or HFC227 propellant fluorinated hydrocarbon, and the polymer coating is formed from the other fluorinated hydrocarbon. Further disclosed is a method of manufacture of the pressurised dispensing apparatus.
Description
PRESSTJRISED DISPENSING APPARATUS
This invention relates to a pressurised dispensing apparatus and a method for manufacturing a pressurised dispensing apparatus. The invention also relates to a pressurised dispensing container for a pressurised dispensing apparatus. Further, the invention relates to a metering valve for a pressurised dispensing apparatus. In particular, the invention relates to a layer or coating formed on one or more surfaces of the pressurised dispensing apparatus, the pressurised dispensing container and/or the metering valve.
It is known in the art to coat parts of aerosol containers with a coating to, say, reduce friction, reduce deposition of a formulation, and/or provide an inert barrier between a container material and a formulation stored in a container or aerosol. The concept behind the inert barrier is to prevent cross-contamination of the material of the container -typically a metal container -in to the formulation which is stored in the container. With asthma inhalers in particular, a patient will inhale the aerosol, and, therefore, it is important that the formulation inhaled does not include cross contaminants from the container.
Numerous coatings are known in the art for this purpose. A problem which has evolved is the chemical stability of the coating in the presence of some formulations and, depending upon the formulation stored, stripping of the coating can occur by the formulation. This has the effect of producing coating contaminants and container contaminants in the formulation to be dispensed. Accordingly, there is a need to develop coatings and formulations which are chemically stable over prolonged periods of storage and working life.
Typically pressurised metered dose inhalers (pMDIs) have a three-year shelf life and it is imperative that throughout this period the inhaler is able to deliver the label claimed dose of the drug. Any loss of drug by degradation or by adhesion to the container or exposed metering valve parts, or by sorption onto or into the elastomers will result in a low dose of drug. Fluorinated coatings on pMDIs are known in the art, as exemplified by EP1066073, which uses C6F4 as the plasma coating material.
However, this material is not used in pMDI formulations, is expensive and not very volatile and consequently will have limited toxicity and exposure data available. The present invention seeks to provided improvements over the
highlighted shortcomings of the prior art.
According to the present invention, there is provided a pressurised dispensing apparatus comprising a pressurised dispensing container and a medicinal formulation, the pressurised dispensing container comprising a container and a valve, wherein at least a portion of one or more internal surfaces of the pressurised dispensing apparatus which come in to contact with said medicinal formulation during storage or dispensing comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein the medicinal formulation comprises a fluorinated hydrocarbon propellant and the layer or coating is formed from a compound comprising the same fluorinated hydrocarbon.
Advantageously, by providing a coating or layer formed from the same fluorinated hydrocarbon as the propellant to be used in the pressurised dispensing apparatus, a good coating or layer is provided which is chemically stable with the medicinal formulation (propellant and active product) over prolonged storage and use. Further, chemical or mechanical stripping of f of the layer or coating is substantially prevented. Further advantageously: * A pMDI valve or container will eventually be filled with formulations that contain HFC134a, HFC227 or both. Thus, any carry over of residual material from the cold plasma process of coating will not present itself as a contaminant.
* HFC134a and HFC227 are used as propellants in pMDIs for which they were originally developed as replacements for the ozone depleting CFCs. As such, they have undergone extensive exposure and toxicological testing.
* HFCs are readily available and are likely to be cheaper than the other cited materials.
* HFCs have low boiling points and, so, it may not be necessary to heat the plasma reaction chamber or the HFC gas.
* I-iFCs will not be seen or viewed as contaminants or foreign material.
* The cold plasma process using the I-iFCs is likely to take significantly less time to achieve a coating of desired quality.
Preferably, one or more internal surfaces of the pressurised dispensing container comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein said medicinal formulation comprises a fluorinated hydrocarbon propellant and the layer or coating on the pressurised dispensing container is formed from a compound comprising the same fluorinated hydrocarbon.
Most preferably, the layer or coating is formed on a surface of the valve and/or the container of the pressurised dispensing container.
The valve may be a metering valve which comprises a valve stem slidable within a valve member, the valve member and valve stem defining a metering chamber, the metering valve further comprising outer and inner seals operative between respective outer and inner ends of the valve member and the valve stem to seal the metering chamber therebetween, one or more internal surfaces of the metering valve comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein the medicinal formulation comprises a fluorinated hydrocarbon propellant and the layer or coating is formed from a compound comprising the same fluorinated hydrocarbon. The layer or coating may be provided on the valve member. The layer or coating may be provided on the valve stem. The layer or coating may be provided on the metering chamber.
Alternatively, the apparatus comprises an actuator for holding the pressurised dispensing container in use, wherein the layer or coating is formed on a valve stem receiving block, a mouthpiece, a spray nozzle, and/or any passageway of the actuator.
The dispensing apparatus may be breath-actuated and may comprise a dose counter for indicating each time the apparatus is actuated.
Most preferably, the fluorinated hydrocarbon is HFC134a. Alternatively, the fluorinated hydrocarbon is HFC227. Of course, the isomers HFC134 and HFC227a may also be used. The isomers may co-exist and/or be essentially separate, depending upon the separation techniques utilised.
Therefore, when coating a pressurised dispensing container with a first isomer of those identified -or other apparatus -or when providing a propellant from a first isomer, some small amount of the other isomer may also be present.
Other fluorinated hydrocarbons such as perfluoro-cyclohexane, perfluoro-hexane, tetrafluoroethylene, trifluoroethylene, vinylidene fluoride, vinyifluoride, fluoroethylene and/or fluoropropylene may be used.
The apparatus may be adapted for nasal or oral use, for example as an asthma inhaler.
The present invention also provides a method of manufacturing a pressurised dispensing apparatus comprising a pressurised dispensing container and a designated medicinal formulation, the method comprising providing a layer or coating, by way of a cold-plasma polymerisation reaction, on at least a portion of one or more internal surfaces of the pressurised dispensing apparatus which come in to contact with the designated medicinal product during storage or dispensing, wherein the designated medicinal product comprises a fluorinated hydrocarbon propellant and the one or more internal surfaces of the pressurised dispensing apparatus are chosen to be treated with the same fluorinated hydrocarbon.
Preferably, the pressurised dispensing container of the pressurised dispensing apparatus is chosen to be treated.
Further preferably, the metering valve of the pressurised dispensing apparatus is chosen to be treated.
Further, the disclosed method is equally applicable to producing layers or coating on pressurised dispensing containers and/or metering valves of the present invention.
In a further aspect, the present invention provides a pressurised dispensing container for a pressurised dispensing apparatus as claimed in any preceding claim, the pressurised dispensing container comprising: a container for storing a designated medicinal formulation to be dispensed; and a valve for controlling dispensing of said designated medicinal formulation; one or more internal surfaces of the pressurised dispensing container comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein, in order to provide chemical compatibility within the pressurised dispensing container, said layer or coating is formed from a fluorinated hydrocarbon compound chosen to comprise the same fluorinated hydrocarbon as a fluorinated hydrocarbon in a propellant of the designated medicinal formulation.
In another aspect of the present invention, there is provided a metering valve for a pressurised dispensing apparatus as claimed in any one of claims 1 to 16 for dispensing a designated medicinal formulation, the metering valve comprising a valve stem slidable within a valve member, the valve member and valve stem defining a metering chamber, the metering valve further comprising outer and inner seals operative between respective outer and inner ends of the valve member and the valve stem to seal the metering chamber therebetween, one or more internal surfaces of the metering valve comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein, in order to provide chemical compatibility within the metering valve, said layer or coating is formed from a fluorinated hydrocarbon compound chosen to comprise the same fluorinated hydrocarbon as a fluorinated hydrocarbon in a propellant of said designated medicinal formulation.
By way of an alternative, the present invention provides a pressurised dispensing apparatus comprising a pressurised dispensing container and a medicinal formulation, the pressurised dispensing container comprising a container and a valve, wherein at least a portion of one or more internal surfaces of the pressurised dispensing apparatus which come in to contact with the medicinal formulation during storage or dispensing comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein, the medicinal formulation is chosen to comprises either an HFC134a propellant or an HFC227 propellant and the layer or coating is formed from the other fluorinated hydrocarbon.
Preferably, the medicinal product comprises HFC134a and the coating or layer is formed from HFC227.
Preferably, the medicinal product comprises HFC227 and the coating or layer is formed from HFC134a.
Preferably, the pressurised dispensing container comprises a pressurised medicinal formulation contained in the container. The pressurised formulation is maintained at a pressure of from 15 to 200 psig or, most preferably, is maintained at a pressure of approximately 60 psig at a room temperature of approximately 20 degrees Celsius.
Preferably, the pressurised formulation comprises a volatile propellant, such as, one or more of HFA134a or HFA227, with or without ethanol being present at a level of from about 1 to about 30%. Most preferably, the pressurised medicinal formulation contains a pharmacologically active product. The formulation may also contain other materials that can act as co-solvents or lubricants.
The pressurised dispensing apparatus may be for use in a pharmaceutical dispensing device, such as, for example, a 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 antiallergics, 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, heparin, morphine, dihydromorphinone, ergotamine, scopolamine, methapyrilene, cyanocobalamin, terbutaline, rimiterol, salbutamol, flunisolide, colchicine, pirbuterol, beclomethasone, orciprenaline, fentanyl, and diamorphirie, streptomycin, penicillin, procaine penicillin, tetracycline, chlorotetracycline and hydroxytetracycline, adrenocorticotropic hormone and adrenocortical hormones, 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, S for example, acetate, benzenesulphonate, benzoate, bicarbonate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochlor�de, edetate, edisylate, estolate, esylate, fumarate, fluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methyibromide, methylnitrate, methylsuiphate, mucate, napsylate, nitrate, pamoate, (ernboriate), 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 ammonium salts and salts of arniries known in the art to be pharmaceutically acceptable, for example glycine, ethylene diamine, choline, diethanolamine, triethanolamine, octadecylamine, diethylamine, triethylamine, l-amino-2-propanol-amino-2- (hydroxymethyl)propane-1,3-d�ol, and 1-(3,4-dihydroxyphenyl) -2 isopropylaminoethanol.
The pharmaceutical will typically be one which is 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. Typical propellants are HFA134a or HFA227 (1-IFC134a / HFC227) and/or isomers thereof.
-10 -The pharmaceutical may, for example, be one which is 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 sa.lbutamol sulphate, salmeterol xinafoate, fluticasone propionate, 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 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 the inner seal, outer seal or gasket may form a seal when abutting the so-called non-sealing components.
In order that the invention may be fully disclosed, embodiments will now be described, by way of example only, -11 -with reference to the accompanying drawings -and the following Examples which serve to illustrate the invention but are not intended to be limiting -in which: Figure 1 is a part-cross-sectional view of a pressurised dispensing apparatus and an actuator housing according to the present invention; and Figure 2 is a part-cross-sectional view of a metering valve according to the present invention.
Referring to the Figures, Figure 1 is a part-cross-sectional view of a pressurised dispensing apparatus and an actuator housing of the present invention. The overall apparatus (pressurised dispensing apparatus and actuator housing) is indicated generally by reference 1. The apparatus 1 generally comprises a pressurised dispensing container 2, which is formed from a container 3 and a valve 4, the valve 4 including a valve stem 5. The pressurised dispensing apparatus is received in a housing 6 of the actuator which is configured to receive the pressurised dispensing container 2 as a sliding fit and which housing 6 is connected to a mouthpiece 7. The housing 6 includes a valve stem receiving block 8, for receiving the valve stem 5 of the pressurised dispensing container 2. Connected to the valve stem receiving block 8 is a spray nozzle 9, for directing a dispensed formulation from the container 2.
In accordance with the present invention, a medicinal formulation (not shown) provided in the pressurised dispensing container 2 comprises a fluorinated hydrocarbon propellant and an active product. Further, one or more internal surfaces of the pressurised dispensing apparatus which come into contact with the medicinal formulation during storage or dispensing comprise a layer or coating -12 -formed from a cold-plasma polymerisation reaction.
Accordingly, an internal surface 3A of the container 3 is coated with a fluorinated hydrocarbon, by a cold-plasma polymerisation reaction. Further, coatings or layers of fluorinated hydrocarbon -from a cold-plasma polymerisation reaction -are provided on an internal surface 10 of the mouthpiece 7, an internal surface 11 of the valve stem receiving block 8, and an internal surface 12 of the spray nozzle 9. The valve 4 is a metering valve, however, a continuous flow valve may also be used. Most preferably, the layer or coating of the one or more surfaces is provided from a cold-plasma polymerisation reaction carried out on HFC134a and the formulation to be dispensed from the container 2 comprises an HFC134a propellant. Of course, in an alternative, the layer and/or coating may be formed from HFC227, following cold-plasma polyrnerisation, and the propellant may be HFC227. In accordance with the invention, the material composition of the layer or coating is selected to conform to the propellant being used in the pressurised dispensing apparatus.
Figure 2 shows a metering valve 20 according to the present invention. The metering valve 20 is suitable for use with the pressurised dispensing container 2 and overall apparatus 1 of Figure 1, and is provided by a valve body 21, which is in contact with a gasket 22 and ferrule 23, for connecting the metering valve 20 with a container (not shown), but which could be connected with the container 3 shown in Figure 1. In addition to the valve body 21, the metering valve includes a valve stem 24, which is slidable within a valve member 25. Together, an internal portion 24A of the valve stem 24 and the valve member 25 provide a metering chamber 26, which provides metered doses of -13 -formulation in a controlled manner through the metering valve 20. In the particular embodiment shown in Figure 2, the metering chamber 26 is provided by an internal portion 24A of the valve stem 24, an internally-facing surface of the valve member 25, and an internally-facing surface of the outer seal 27. Respective outer and inner ends of the valve member 25 are provided with outer and inner seals 27, 28, which seal together outer and inner ends of the valve member and the valve stem 24, to seal the metering chamber 26 therebetween.
In order to maintain closure of the metering valve in a rest position, a spring 29 is provided to biase the valve stem 24 in to its closed position, as shown in Figure 2.
The spring 29 acts against a first flange 30 provided on the valve stem 24, which flange 30 is located outside of the metering chamber 26. In the closed position of the metering valve 20, a second flange 31, which is provided within the metering chamber 26, is located against the outer seal 27, which maintains closure of the metering valve 20 whilst retaining the inner end of the valve stem 24 within the metering chamber 26 and the inner seal 28. Apertures 32 and 33 are linked by a channel (not shown) which allows a formulation to be dispensed to enter the metering chamber 26, when the valve stem 24 is provided in its closed position of Figure 2. Aperture 34 connects with a hollowed portion 35 of an external portion of the valve stem 24 which aperture 34, once the valve stem is depressed, enters the metering chamber 26 and allows a formulation to be dispensed to exit the metering chamber 26, through the aperture 34 and along the hollowed portion 35 of the valve stem 24.
In accordance with the present invention, one or more internal surfaces of the metering valve 20 comprise a layer -14 -or coating formed from a cold-plasma polymerisation reaction. The layer or coating is chosen to correspond to the propellant of the medicinal formulation to be dispensed through the metering valve 20 and the layer or coating is formed from a compound comprising the same fluorinated hydrocarbon as that used as the propellant. Therefore, a layer or coating formed from a cold-plasma polyrnerisation reaction is provided on a surface of the hollowed portion 35 of the valve stem 24, an outer surface of the internal portion 24A of the valve stem 24, an internally-facing surface of the valve member 25, and an internally-facing surface of the outer seal 27. Therefore, the metering chamber 26 can be provided with a layer or coating of a fluorinated hydrocarbon which matches the fluorinated hydrocarbon propellant that will be dispensed through the metering valve 20. As described with reference to Figure 1, preferably the propellant and the layer or coating are formed from HFC134a. Alternatively, they may be formed from HFC227.
-15 -
Example 1
XPS measurements were performed with a Kratos Axis Ultra Spectrometer operating at a base pressure of 3x109 Torr. The samples were irradiated with monochromatic Al Kc x-ray (1486.6 eV) using an X-Ray analysis spot size of 700 pm x 300 pm and around 225 W power. Survey spectra were recorded with pass energy of 160 eV, from which the surface elemental compositions were determined. In addition, selected high resolution spectra were recorded with pass energy of 20 eV, from which the chemical states of those elements were determined. Charge compensation for electrically insulating specimens was achieved using a beam of magnetically focussed electrons as a flood current. The standard electron take off angle used for analysis is 9O giving a maximum analysis depth lying in the range 5 -8 nm.
Plasma depositions were carried out in a Nanotech Plasmaprep 100 RF plasma asher modified for the purpose of this work. A gas blending system using mass flow controllers -allowing for blends of up to four gases -was used as a gas feed. For one of the monomers, HFC134a, blending with argon was investigated as a means to moderate the deposition rate. Depositions using the neat gas were also investigated. For the}-1FC227 monomer, depositions were carried out solely using the neat gas. A clean glass slide was used as a support for the polybutylene teraphathalate (PBT) metering chambers to be coated in the quartz plasma chamber (barrel type, 10 cm diameter, 16 cm in length). The glass slide was located approximately half way along the length of the chamber and towards the bottom half of the chamber so that the metering chambers, placed in the central area of the glass slide during deposition, were located around 2.5 cm for the bottom wall of the chamber. The -16 - metering chambers were placed so that the flat bottom -where surface analysis was subsequently carried out -was facing up (i.e. open side facing down on the glass side).
Initial pre-cleaning of the equipment was conducted using an oxygen plasma to burn off any possible organic contaminants in the deposition chamber. Between the two monomer depositions, the chamber walls were thoroughly mechanically (fibre glass brush) and chemically (high purity acetone) cleaned of the thickly deposited material to avoid any cross-contamination.
Table 1 shows for comparison the surface compositions of two PBT samples prior to deposition (PET #1 and PBT #2), a fluorocarbon reference material poly(tetrafluoroethylene), PTFE], a PET sample treated by Bespak with C6F14 as described in patent EP1066073 and two initial trials of depositions on glass slides. It is clear that both monomers HFC134a and HFC227 lead to the deposition of a highly fluorinated coating which covers completely the glass slide substrate.
The compositions of the two types of coatings are different with the HFC134a coating slightly deficient in fluorine compared to the I-1FC227 coating. There are also significant variations in the levels of the fluorocarbon functionalities detected which result from depositions under almost comparable conditions. However, the composition of this first trial HFC227 coating is closely similar to that of the Bespak coating.
Owing to high deposition rates obtained with the HFC134a monomer and the moderating effect of argon as a blending gas, various argon/HFC134a gas blends were investigated (see Note 1 below). Additional deposition parameters including deposition time and RF power were also investigated to monitor their influence on the surface -17 -composition of the coating. XPS analysis of the deposited coatings on PBT is reported in Table 2. The composition of the coating is clearly tuneable with a change of the deposition parameters. A particularly dramatic effect is observed for an increase in the RF power when the partial pressure of monomer in the gas blend is low. Under these conditions, the elemental composition (and F:C ratio) of the coating is closer to that of the Bespak treated sample, although some differences can be found in the relative levels of fluorocarbon functionalities. The coatings deposited at a low RF power over the range of gas blend ratios investigated all produced coatings deficient in fluorine compared to the Bespak coating. Depositions on the two types of PBT were found to be similar with coatings thicker than the sampling depth of the technique (5 -8 nm).
Low levels of oxygen and nitrogen were incorporated into the coatings which probably originate from residual gas in the chamber and/or impurities in the monomer gas. Oxygen is also seen to be deposited in the Bespak coating.
For HFC227 depositions, no gas blending was used, i.e. the monomer was fed neat into the plasma chamber. It is clear from the results that the range of parameters investigated had little influence on the surface composition of the coating with only a small decrease in the fluorine level noted with increasing pressure (Table 3). As for HFC134a, depositions on the two types of PBT were similar and the coating was thicker than the sampling depth of the technique (5 -8 nm). As noted for the trial deposition on glass slide, the elemental and functional composition of the HFC227 coating on PBT is closely similar to that of the Bespak coating.
-18 -Note 1 -Explanation of sample descriptions in Tables 1 to 3: The figures between brackets in the sample description represent the respective mass flow controller settings used in the gas blend. The mass flow controllers were not calibrated for the gases used and therefore the blend ratios should only be taken as indicative values since the gases used (argon, HFC134a and HFC227) have different heat capacities and densities. As such, ignoring differences between the gases, (100) represents a neat gas, (100/100) represents theoretically a 50/50 blend. (100/So) represents theoretically a 66.66/33.33 blend and (100/20) represents theoretically a 83.33/16.77 blend.
* 20W and 100W represent the RF powers used for the depositions.
* Typical deposition times varied between 10 mins and 30 mins.
* Deposition pressures were carried out at 120 mTorr, 140 mTorr and 400 mTorr.
The XPS data provided in Tables 1 to 3 is derived from the survey and key high resolution spectra obtained on the samples analysed. Table 1 lists the compositions in atomic (At.%) derived from the survey spectra. The quantification model used assumes that the sample volume probed is homogenous.
The error values c are calculated from the statistical noise on the data and represent one standard deviation confidence limits; i.e. there is a 68% probability that the true composition lies between the calculated composition given in the results tables c � o. There is a 95% -19 -probability that the true composition lies between c � 2 o.
If the a value is comparable to c, the element is at or very close to its detection limit for the analysis conditions used. Note that the absolute accuracy of the composition results depend upon a number of factors, but the error values enable the significance of compositional differences between physically similar samples to be assessed.
-20 -Table 1: Surface compositions in At. % derived from sutvey spectra GlaaB Glass Slide Slide PDT #1 PBT #2 Bespak HFC134a HFC227 Untreated Untreated PTFE Treated (100) (100) component component control 20W 20W 10mm 10mm, Element l4OmTorr l2OmTorr Carbon 81.9 79.3 33.3 44.7 56.4 44.].
_______ 0.2 0.2 0.2 0.2 0.2 0.2 C-H 57.4 51.7 ND ND ND ND C-0 12.5 13.5 ND ND ND ND 0-C=0 10.0 11.4 ND ND ND ND pj* sat 2. 0 2. 7 ND ND ND ND CH-CH-CF,, ND ND ND 2.7 ND 0.7 CH-CF, ND ND ND 13.8 27.5 12.8 CF ND ND ND 7.4 13.1 10.2 CF2 ND ND 33.3 10.9 7.8 10.4 CF3 ND ND ND 9.9 7.9 10.0 Fluorine ND 66.7 54.3 42.9 55.3 a _____________ _____________ 0.2 0.2 0.2 0.2 Oxygen 18.1 20.7 0.94 0.71 0.27 a 0.2 0.2 0.06 0.06 0.06 0C 8.0 9.2 NR NR NB NB 0-C 10.]. 11.5 NR NB NB NB Nitrogen 0. 34 a ____________ ____________ ____________ ____________ ____________ 0.08 F:C ratio 2.00 1.2]. 0.76 1.25 a 0.02 0.01 0.01 0.01 CSMA File b29a0812 b29a0813 Kratos PTFE b29a0810 b24a 0802 b28a0801 ND: Not Detected, NR: Not Recorded.
-21 -Table 2: Surface compositions in At. % derived from survey spectra PET *1 PET #1 PET #1 PET #1 PET #2 PET #1 PBT #2 PBT #1 PBT #1 Ar/SPC134a Ar/EPC134a Ar/HFC134a EPC134a EFC134a AzIHPC134a Ar/HFC134 Ar/RFC134a EFC134 (100/20) (100/50) (100/100) (100) (100) (100/20) (100/20) (100/20) (100) 20W, 20W, 20W, 20W, 20W, 20W, 20W, 100W, 100W, 10mm, 10mm, 10mm, 10mm, 10mm, 30mm, 30mm, 10mm, 10mm, Element L20morr 120mror 120i'rorr l2OmTorr l2OmTorr l2OmTorr l2OutTorr 120mToxr L2ouftorr Carbon 50.5 54.3 55.3 56.1 55.8 51.2 52.4 43.6 54.3 a 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
C -H ND ND ND ND ND ND ND ND ND
C -0 ND NI) NI) ND ND ND ND ND ND 0-C.'O ND NI) ND ND ND ND ND NI) ND P1 * sat ND NI) ND ND ND ND ND ND ND CH-CH-CF 1.4 MI) 1.3 ND ND 1.4 2.1 0.5 0.7 CH-CF 15.8 22.9 23.7 27.2 27.0 16.6 17.0 9.8 23.9 Cs' 17.0 17.3 15.3 13.6 13.4 17.3 17.3 11.5 14.5 CF2 12.1 9.0 8.6 7.7 7.5 11.6 11.4 14.9 8.3 CF3 4.2 5.1 6.4 7.7 7.9 4.3 4.6 6.8 6.9 Fluorine 47.8 44.5 43.8 42.6 43.0 47.8 46.5 55.0 44.4 a 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 oxygen 1.07 1.00 0.85 1.24 1.21 0.73 0.78 0.62 1.36 a 0.06 0.07 0.07 0.08 0.07 0.07 0.07 0.06 0.07 0=C NR MR MR NR MR NR MR NR MR 0-C NR NR MR MR MR NR MR NR NR Nitrogen 0.7 0.19 0.3 0.3 0.8 a 0.2 0.09 _________ _________ ________ 0.2 0.1 0.2 ________ F:C ratio 0.95 0.82 0.79 0.76 0.77 0.93 0.89 1.26 0.82 a 0.01 0.01 o.oj. 0.01 0.01 0.01 o.oi 0.01 0.0].
CSMPJ
File b25a0804 b25a0803 b25a0805 b25a0801 b25a0806 b29a0802 b29a0801 b29a0803 b29a0804 ND: Not Detected, NR: Not Recorded.
-22 -Table 3: Surface compositions in At. % derived from survey spectra PBT #1. PBT #1 PBT #1 PBT #1 PBT #1 PBT #1 HFC227 HFC227 HFC227 HFC227 HFC227 HFC227 (100) (100) (100) (100) (100) (100) 20W, 20W, 20W, 100W, 100W, 100W, 10mm, 30mm, 10mm, 10mm, 30mm, 30mm, l2OmTor l2OmTor.400mTor l2OmTor l2OmTor l2OmTor Element r r r r r r Carbon 44.2 44.0 46.1 44.]. 44.2 43.9 ___________ 0.2 0.2 02 0.2 0.2 0.2 C-H ND NI) ND ND ND ND
C-O ND ND ND ND ND ND
0-C=O ND ND ND ND ND ND j* sat ND ND ND ND ND ND
CH-CH-
CF ND ND ND ND ND ND
CH-CF 12.9 13.0 16.0 12.7 12.7 12.8 CF 10.4 10.2 10.4 10.4 10.4 10.3 CF2 10.7 10.6 9.9 11.2 11.2 11.2 CF3 10.3 10.2 9.9 9.8 9.8 9.6 Fluorin e 55.0 55.3 53.2 55.2 55.2 55.4 ___________ 0.2 0.2 0.2 0.2 0.2 0.2 Oxygen 0.45 0.46 0.30 0.48 0.43 0.44 0.06 0.06 0.06 0.06 0.06 0.06 OsC NR NR NR NR NR NR o -C NR NR NR NR ___________ Nitroge n 0.34 0.2 0.4 0.2 0.3 0.3 ___________ 0.08 0.2 0.1 0.2 0.1 0.1 F:C ratio 1.25 1.26 1.15 1.25 1.25 1.26 0.01 0.01 0.01 0.01 0.01 0.01 CS!4A File b29a0806 b29a0811.b29a0807 b29a0805 b29a0808 b29a0809 ND: Not Detected, NR: Not Recorded.
-23 -
Example 2
A second series of cold-plasma experiments were carried out using a modified plasma reaction chamber. PET metering chambers were tumbled during deposition in a device purposely designed and manufactured for this work, to ensure coating of all surfaces of the samples. The tumbling device consists of a cylindrical cage (5 cm diameter, 10 cm in length), with a wide open structure and is made of PET.
This fits in the central region of the quartz plasma chamber (barrel type, 10 cm diameter, 16 cm in length) . The cage is fixed to a vacuum rotary drive fitted to a replacement glass door on the plasma reactor. Rotation of the cage is supported by an external motor (-45 RPM). XPS measurements were performed as described above in Example 1 and these were carried out on both the internal and external surfaces of the treated metering chambers. These results are shown in tables 4 and 5 below.
Plasma depositions were carried out on batches of PET MDI chambers, using the HFC227 and HFC134a monomers. For HFC134a, two deposition conditions were used with different gas blends with argon. HFC227 was used as a neat monomer.
Both the outer surface on the flat bottom and the internal surface of the same components were analysed. From this work, the following observations could be made: * The surface compositions of components treated with the tumbling device are comparable to those previously treated without this device under the same deposition conditions, indicating little or no perturbation introduced by the new experimental setup. Deposition times had to be increased to compensate for the partial screening of the components under treatment to the reactive species by components of the tumbling cage.
-24 - * As previously noted, the use of HFC227 monomer resulted in depositions with fluorocarbon functionalities closely matching those obtained by Bespak control depositions.
* The Ar/HFC134a gas blend with a low reactive monomer content (100/20 blend) resulted in a coating with increased fluorination and compositionally more comparable to that of the Bespak treated samples compared to a blend with a higher monomer fraction (100/100 blend) . In the latter case, the lower fluorination and concomitant higher hydrogenation of the coating is likely to reduce the hydrophobicity of the coating. Therefore, the Ar/HFC134a (100/20) gas blend is likely to be a more suitable system for future depositions involving this monomer.
* There are small compositional differences between outer and inner surfaces of the treated components where slightly higher fluorination is observed for the internal surface.
-25 -Table 4: Surface compositions in At. % derived from survey and high resolution spectra Top outer surface PBT #1 PBT *1 PBT #1 PBT #1 PBT #1 AS received Bespaic HVC227 ArIHFC134a Ar/HFC134a TJntreated treated (100) (100/20) (100/100) mTorr 120 ntTorr 120 mTorr 100W 100W 100 W Element 2 hours 2 hours 1 hour Carbon 80.8 46.2 45.9 46.8 49.9 _________ 0.1 0.2 0.2 0.2 0.2 C-c; C-H 56.5 ND ND ND ND C-0 12.4 ND ND ND ND o-C=o 9.9 ND ND ND ND pj* sat 1.9 ND ND ND ND CH-CH-CF ND 2.2 2.4 1.4 0.5 CH-CF ND 14.3 13.2 13.9 17.5 CF ND 9.0 9.8 11.9 13.5 CF2 ND 10.6 11.3 13.2 11.0 CF3 ND 10.1 9.3 6.5 7.4 Fluorine ND 52.9 53.3 52.]. 49.1 _____________ ______________ 0.2 0.2 0.2 0.2 Oxygen 19.2 0.85 0.77 1.04 0.99 0.]. 0.08 0.07 0.09 0.08 o=C 8.2 0-C 11.0 NR NR NR NR F:C ratio 1.14 1.16 1.11 0.98 0.01 0.01 0.01 0.01 CSMP. Pile b25d0806.b25d0805 b25d0801 b25d0804 b25d0803 ND: Not Detected, NR: Not Recorded.
-26 -Table 5: Surface compositions in At. % derived from survey and high resolution spectra Internal surface PBT *1 PBT #1 PBT *1 PBT #1 PBT #1 Aa received Bespak HFC227 Ar/HPC134a Ar/PC134a entreated treated (100) (100/20) (100/100) mTorr 120 mTorr 120 mTorr 100W 100W 100 W Element 2 hours 2 hours 1 hour Carbon 81.7 42.6 44.4 42.5 50.2 0 0.2 _____ 0.2 _____ 0.3 _____ 0.2 0.2 C-C; C-H 55.9 ND ND ND ND C-O 15.2 ND ND ND ND 0-C=O 8. 5 ND ND ND ND pj* sat 2.1 ND ND ND ND CH-CH-CF ND 1,1 2.4 0.7 2.5 CH-CF ND 13.2 13.4 9.5 18.3 CF ND 7.7 9.3 11.1 12.7 CF2 ND 10.7 10.7 15.0 10.8 CF3 ND 9.9 8.6 6.2 6.0 Fluorine ND 56.7 54.5 56.7 48.4 0 _______________ 0.2 0.3 0.2 0.2 Oxygen 18.3 0.7 1.1 0.8 1.4 0 0.2 0.1 0.2 0.1 0.1 0=C 7.1 0-C 11.2 NP. NP. F:C
ratio 1.33 1.23 1.33 0.96 a 0.01 0.01 0.01 0.01 CSMA File b25d0813 b25d0810 b25d0811 b25d0809 b25d0812 ND: Not Detected, NR: Not Recorded.
Claims (24)
- -27 -CLAIMS: 1.) A pressurised dispensing apparatus comprising a pressurised dispensing container and a medicinal formulation, the pressurised dispensing container comprising a container and a valve, wherein at least a portion of one or more internal surfaces of the pressurised dispensing apparatus which come in to contact with said medicinal formulation during storage or dispensing comprise a layer or coating formed from a Cold-plasma polymerisation reaction, wherein the medicinal formulation comprises a fluorinated hydrocarbon propellant and the layer or coating is formed from a compound comprising the same fluorinated hydrocarbon.
- 2.) An apparatus as claimed in claim 1, wherein one or more internal surfaces of the pressurised dispensing container comprise a layer or coating formed from a cold-plasma polyrnerisation reaction, wherein said medicinal formulation comprises a fluorinated hydrocarbon propellant and the layer or coating on the pressurised dispensing container is formed from a compound comprising the same fluorinated hydrocarbon.
- 3.) An apparatus as claimed in claim 2, wherein the layer or coating is formed on a surface of the valve and/or the container of the pressurised dispensing container.
- 4.) An apparatus as claimed in any preceding claim, wherein the valve is a metering valve which comprises a valve stem slidable within a valve member, the valve member and valve stem defining a metering chamber, the metering valve further comprising outer and inner seals operative between respective outer and inner ends of the valve member and the -28 -valve stem to seal the metering chamber therebetween, one or more internal surfaces of the metering valve comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein the medicinal formulation comprises a fluorinated hydrocarbon propellant and the layer or coating is formed from a compound comprising the same fluorinated hydrocarbon.
- 5.) An apparatus as claimed in claim 4, wherein the layer or coating is provided on the valve member.
- 6.) An apparatus as claimed in claim 4 or claim 5, wherein the layer or coating is provided on the valve stem.
- 7.) An apparatus as claimed in any one of claims 4 to 6, wherein the layer or coating is provided on the metering chamber.
- 8.) An apparatus as claimed in any preceding claim, further comprising an actuator for holding the pressurised dispensing container in use, wherein the layer or coating is formed on a valve stem receiving block, a mouthpiece, a spray nozzle, and/or any passageway of the actuator.
- 9.) An apparatus as claimed in claim 8, wherein the dispensing apparatus is breath-actuated.
- 10.) An apparatus as claimed in any preceding claim, further comprising a dose counter for indicating each time the apparatus is actuated.-29 -
- 11.) An apparatus as claimed in any preceding claim, wherein the fluorinated hydrocarbon is HFC134a or the isomer HFC134.
- 12.) An apparatus as claimed in any one of claims 1 to 10, wherein the fluorinated hydrocarbon is HFC227 or the isomer HFC227a.
- 13.) An apparatus as claimed in any preceding claim, wherein the apparatus is adapted for nasal or oral use, for example as an asthma inhaler.
- 14.) A method of manufacturing a pressurised dispensing apparatus comprising a pressurised dispensing container and a designated medicinal formulation, the method comprising providing a layer or coating, by way of a cold-plasma polymerisation reaction, on at least a portion of one or more internal surfaces of the pressurised dispensing apparatus which come in to contact with the designated medicinal product during storage or dispensing, wherein the designated medicinal product comprises a fluorinated hydrocarbon propellant and the one or more internal surfaces of the pressurised dispensing apparatus are chosen to be treated with the same fluorinated hydrocarbon.
- 15.) A method as claimed in claim 14, wherein the pressurised dispensing container of the pressurised dispensing apparatus is chosen to be treated.
- 16.) A method as claimed in claim 14 or claim 15, wherein a metering valve of the pressurised dispensing apparatus is chosen to be treated.-30 -
- 17.) A pressurised dispensing container for a pressurised dispensing apparatus as claimed in any preceding claim, the pressurised dispensing container comprising: a container for storing a designated medicinal formulation to be dispensed; and a valve for controlling dispensing of said designated medicinal formulation; one or more internal surfaces of the pressurised dispensing container comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein, in order to provide chemical compatibility within the pressurised dispensing container, said layer or coating is formed from a fluorinated hydrocarbon compound chosen to comprise the same fluorinated hydrocarbon as a fluorinated hydrocarbon in a propellant of the designated medicinal formulation.
- 18.) A metering valve for a pressurised dispensing apparatus as claimed in any one of claims 1 to 16 for dispensing a designated medicinal formulation, the metering valve comprising a valve stem slidable within a valve member, the valve member and valve stem defining a metering chamber, the metering valve further comprising outer and inner seals operative between respective outer and inner ends of the valve member and the valve stem to seal the metering chamber therebetween, one or more internal surfaces of the metering valve comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein, in order to provide chemical compatibility within the metering valve, said layer or coating is formed from a fluorinated hydrocarbon compound chosen to comprise the same fluorinated hydrocarbon as a fluorinate& hydrocarbon in a propellant of said designated medicinal formulation.-31 -
- 19.) A pressurised dispensing apparatus comprising a pressurised dispensing container and a medicinal formulation, the pressurised dispensing container comprising a container and a valve, wherein at least a portion of one or more internal surfaces of the pressurised dispensing apparatus which come in to contact with the medicinal formulation during storage or dispensing comprise a layer or coating formed from a cold-plasma polymerisation reaction, wherein, the medicinal formulation is chosen to comprise either an HFC134a propellant or an HFC227 propellant and the layer or coating is formed from the other fluorinated hydrocarbon.
- 20.) An apparatus as claimed in claim 19, wherein the medicinal product comprises 1-!FC134a and the coating or layer is formed from HFC227, and/or the isomers thereof.
- 21.) An apparatus as claimed in claim 19, wherein the medicinal product comprises IiFC227 and the coating or layer is formed from HFC134a, and/or the isomers thereof.
- 22.) A pressurised dispensing apparatus for dispensing a medicinal formulation substantially as herein described, with reference to the accompanying drawings and/ordescription.
- 23.) A pressurised dispensing container for dispensing a medicinal formulation substantially as herein described, with reference to the accompanying drawings and/ordescription.-32 -
- 24.) A metering valve for a pressurised dispensing apparatus or container substantially as herein described, with reference to the accompanying drawings and/or description.
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|---|---|---|---|
| GB0810614A GB2460843A (en) | 2008-06-10 | 2008-06-10 | Cold plasma polymer coated pressurised dispensing apparatus |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0810614A GB2460843A (en) | 2008-06-10 | 2008-06-10 | Cold plasma polymer coated pressurised dispensing apparatus |
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| GB2460843A true GB2460843A (en) | 2009-12-16 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013037006A1 (en) * | 2011-09-14 | 2013-03-21 | Pacifitech Pty Ltd | Plasma treatment of halogenated compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004093950A1 (en) * | 2003-04-22 | 2004-11-04 | Glaxo Group Limited | A medicament dispenser |
| US20080081129A1 (en) * | 2004-12-23 | 2008-04-03 | Nasser Beldi | Method for Treating a Polymer Material, Device for Implementing this Method and Use of this Device for Treating Hollow Bodies |
-
2008
- 2008-06-10 GB GB0810614A patent/GB2460843A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004093950A1 (en) * | 2003-04-22 | 2004-11-04 | Glaxo Group Limited | A medicament dispenser |
| US20080081129A1 (en) * | 2004-12-23 | 2008-04-03 | Nasser Beldi | Method for Treating a Polymer Material, Device for Implementing this Method and Use of this Device for Treating Hollow Bodies |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013037006A1 (en) * | 2011-09-14 | 2013-03-21 | Pacifitech Pty Ltd | Plasma treatment of halogenated compounds |
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