EP1357964A1 - Aerosols a usage medicinal - Google Patents
Aerosols a usage medicinalInfo
- Publication number
- EP1357964A1 EP1357964A1 EP02702021A EP02702021A EP1357964A1 EP 1357964 A1 EP1357964 A1 EP 1357964A1 EP 02702021 A EP02702021 A EP 02702021A EP 02702021 A EP02702021 A EP 02702021A EP 1357964 A1 EP1357964 A1 EP 1357964A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- aerosol
- product
- medicinal
- shroud
- formulation
- 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- Withdrawn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
Classifications
-
- 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
- B65D83/384—Details of the container body comprising an aerosol container disposed in an outer shell or in an external container
-
- 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
Definitions
- This invention relates to medicinal aerosols and in particular to metered dose inhalers (MDI's) which are used to dispense medicament to the respiratory system of a patient.
- MDI's metered dose inhalers
- Medicinal aerosol formulations in pressurised containers have been available for over forty years. For most of this time, chlorofluorocarbons have been used as the propellants. Drugs have been formulated either as solutions or as suspensions, depending on their solubility properties and other factors. Following environmental concerns over their use, other propellants have been introduced, as this has presented a challenge to reformulate or to introduce new drugs, as well as an opportunity to provide improved pharmaceutical performance.
- HFA 134a 1 ,1,1 ,2-tetrafluoroethane
- HFA 227 1,1,1,2,3,3,3-heptafluoro ⁇ ropane
- micronised drug When formulating suspensions, micronised drug is dispersed in a propellant system with other ingredients added as appropriate for maintaining the stability of the formulation.
- One aspect of stability is the homogeneity of the dispersed drug, which can sediment (settle) or cream (float) depending on the density difference between drug and propellant, or it can flocculate, which requires some degree of agitation to deflocculate it.
- Such challenges are presented when formulating suspensions of any drug, but are particularly important when high potency drugs, such as Formoterol, Fluticasone Propionate, Salmeterol, Procaterol and Ipratropium and salts thereof are formulated.
- the concentration of drug required is lower than for less potent drugs. Sedimenting, creaming or flocculating drug leads to greater inhomogeneity of the contents that in turn may lead to delivery of incorrect doses when the formulation is dispensed from the metering valve.
- the concentration of the components of the medicinal aerosol formulation will be selected depending upon the volume of the can from which the formulation will be dispensed and the fill weight i.e. the total number of doses, of the formulation which will be introduced into the can.
- the other ingredients of the aerosol formulation may also vaporise to some extent depending upon the vapor pressure of the ingredient.
- the result will be that the liquid formulation metered and dispensed by the valve will contain less of the most volatile ingredients and more of the less volatile ingredients compared to the situation when using a can of smaller volume. This concentration of the less volatile ingredients may result in the drug delivery varying from the target dose by an unacceptable margin.
- the medicinal aerosol formulation comprises relatively non-volatile components, such as ethanol, the concentration of such components may deleteriously affect the spray of droplets which are dispensed. Higher concentrations of ethanol may result in the formation of coarser droplets and the respirable fraction of the dose may be reduced.
- the Andersen data may be represented in terms of the throat-to-jet fraction and the fine particle fraction, which includes plates 4 to 6.
- MDI's are used in conjunction with an actuator which comprises a housing to contain the aerosol can, a nozzle block which accommodates the valve and directs the dose towards a mouthpiece or nasal adapter through which the patient receives the medicament.
- the actuator may be of the 'press-and-breathe' type which requires that the patient actuates the aerosol manually pressing on the can, or the actuator may be breath-actuated such that the aerosol is fired automatically as the patient inspires through the mouthpiece.
- MDI's having a different number of total doses e.g. 30, 45, 60, 120, 200 etc.
- the selection of these may depend upon the nature of the ailment, the dosage regime for the treatment and the expected duration of the treatment etc.
- GB-2267936 discloses an aerosol vial having secured to its outer surface a plastics shroud which covers the base of the vial and extends at least halfway up the sidewall of the vial such that it increases the width of the vial by at least 2mm and the height of the vial by at least 5mm.
- the patent addresses the inherent disadvantages in using small aerosol vials including:
- the patent does not recognise the problem associated with the development of aerosol products having different numbers of total doses to be delivered.
- a medicinal aerosol product comprising a metal aerosol can comprising a circular base, cylindrical sidewall extending from the base to an open end to which is attached a metered dose dispensing valve, the aerosol can containing a medicinal aerosol formulation characterised in that the aerosol can is secured within a metal shroud which covers the base of the aerosol can and extends at least partially up the sidewall of the aerosol can to provide the product with external dimensions substantially equivalent to that of an aerosol can of larger dimensions.
- a method of manufacturing a medicinal aerosol product which comprises the steps of:
- a medicinal aerosol formulation for use at a first fill weight in a first aerosol can equipped with a metered dose dispensing valve, the first aerosol can comprising a circular base and a cylindrical side wall extending from the base to a shoulder region terminating in a neck to which said valve is attached,
- the second aerosol can comprising a circular base and a cylindrical side extending from the base to a shoulder region terminating in a neck to which said metered dose dispensing valve is attached, the aerosol formulation being filled at a second fill weight which is less than said first fill weight such that when dispensed from said second can through said metered-dose dispensing valve the emitted dose will exhibit pharmaceutical characteristics substantially identical to the dose characteristics obtained if said formulation had been filled at said first fill weight in said first can and dispensed therefrom through said metered dose dispensing valve,
- said second can is secured within a metal shroud which covers the base of the can and extends at least partially up the sidewall to provide the second with external dimensions substantially identical to said first can.
- the invention further provides a method of producing a second metered dose inhaler product comprising a medicinal aerosol formulation, aerosol container, valve and actuator that produces fewer doses than a first metered dose inhaler product, where the dose delivery characteristics, formulation, valve size and actuator are the same in the second product as the first product, by using less of the formulation in a smaller aerosol container for the second product, in conjunction with an adaptor to permit the smaller aerosol container to fit properly in the actuator.
- the adapter is generally constructed and arranged so that the combination of the adapter and smaller aerosol container has substantially the same outer dimension as that of the first metered dose inhaler product.
- the pharmaceutical characteristics defined here are the amounts of drug delivered per dose and/or the throat-to-jet and fine particle fractions of Andersen data at various stages of emptying of the can.
- the invention provides a simple and effective system which enables an identical medicinal aerosol formulation to be used in a range of aerosol products having different fill weights, which products may be used in the same actuator. Furthermore, the products may be manufactured using the same automatic machinery and the same size labelling and/or packaging may also be used in conjunction with the product.
- the use of the body of a larger can to form such a shroud has significant advantages since the resulting shrouded can will have dimensions and properties which are not significantly different from a product formed from the larger can.
- the shrouded can may readily be handled on the automatic lines designed to handle the larger can since the weight, dimensions and frictional properties of the shrouded can are similar.
- the outer surface of the shrouded can will allow use of the same size labels as the larger can and the external dimensions of the aerosol product formed with the shrouded can will allow use of the same packaging and packaging machinery.
- the aerosol product formed of the shrouded can may be used in the actuators designed for use with the larger can with comparable performance.
- the airflow characteristics will not alter substantially since the shrouded can has substantially identical dimensions to the product formed of the larger can and the shrouded can will fit within a breath actuated actuator and co-operate with the triggering mechanism in the same manner as an aerosol product formed from the larger can.
- a bead may be conveniently formed by a roller urged against the outside of the larger can to form a circumferential recess in the outside surface of the can resulting in a bead on the inner surface of the can.
- this operation may be conducted on a standard centre lathe e.g. utilising a roller and support peg so that the bead on the can can be consistently reproduced.
- the roller and peg are mounted on the centre lathe so that the bead can be formed with the required degree of accuracy.
- the can is simply placed on to the rotating support peg, after which the roller is moved into contact with the outside wall of the can and then pushed in slightly to form a bead.
- the inner can is then placed within the shroud so that the base of the inner can contacts the bead.
- the shroud may be secured to the inner can by deformation of the shroud to obtain an interference fit.
- the interference fit is achieved by means of three or more dimples pushed in to the outside of the shroud such that the internal surface of the shroud in the region of the dimples is forced against the external surface of the can.
- the dimples may readily be formed by a punch and die arrangement, the depth of the dimples being controlled using a stop mechanism.
- the dimples are arranged symmetrically around the circumference of the shroud such that if three dimples are used they will be spaced approximately 120° apart.
- the interference fit is obtained by reducing the diameter of the shroud e.g. by use of a recone punch and die.
- the recone punch and die may conveniently be fitted to a Fly-Press so that the shrouds may be aligned and drawn down to a set length each time.
- This technique secures the shroud firmly to the can with a water-tight seal such that the shrouded can may be immersed in a water bath without ingress of water between the can and the shroud.
- the shroud must extend up the sidewall of the can for a sufficient length to allow formation of an interference fit.
- the shroud extends substantially to the shoulder region of the can to provide a substantially continuous outer sidewall to the aerosol product.
- the base of the shroud may comprise an aperture to ensure that any air trapped between the can and the shroud is at ambient pressure.
- the can size is chosen according to the required fill weight. A range of can sizes can be filled with aerosol formulation from a batch, then tested for dose characteristics. The can size with the closest match to the comparative product is then selected.
- Typical values are 8.0, 10.3, 13.6, 14.2 and 16.25.
- a comparative product of 120 doses in a 16.25 ml can has matched dose characteristics with a product of 60 doses in an 8.0 ml can, the 8.0 ml can being enshrouded with a shroud made from a 16.25 ml can.
- aerosol formulation fill weight and volume of the can can readily be determined by a person skilled in the art.
- the invention finds particular utility for use with formulations comprising non-volatile ingredients, such as ethanol, which have been found to be more problematic than formulations which simply consist of aerosol propellant and drug.
- FIG. 1 represents a diagram of an aerosol product in accordance with the invention
- FIG. 2 represents a diagram of a further aerosol product in accordance with the invention.
- Figure 3 represents a diagram of a further aerosol product in accordance with the invention.
- the aerosol product generally shown at 2 comprises an aerosol can 4 having a circular base 6 and a cylindrical sidewall 8 extending from the base 6 to a shoulder region 10 terminating in a neck 12.
- a metered dose dispensing valve generally shown at 14 comprises a valve stem 16 and a valve ferrule 18 which is crimped to the neck 12 of the aerosol can.
- the aerosol can is generally made from aluminium e.g. by drawing.
- the aerosol can 4 is secured within a shroud generally shown at 20.
- the shroud is formed from an aerosol can of larger size and comprises a circular base 22 and cylindrical sidewall 24.
- a circumferential bead 26 is formed in the sidewall 24 to act as a stop for the aerosol can 4.
- the base 6 of the aerosol can 4 abuts the bead 6 and prevents the can 4 from further movement into the shroud 20.
- the cylindrical sidewall 24 of the shroud extends to the shoulder region 10 of the aerosol can 4.
- the aerosol can 4 is secured to the shroud 20 by means of three dimples 28 pressed into the shroud such that the internal surface of the shroud is forced into contact with the external surface of the aerosol can 4 in the region of the dimples 28.
- the shrouded can may be used on a handling line and with all of the automatic handling machinery designed for use with an aerosol can from which the shroud 20 is made.
- the embodiment shown in Figure 2 differs from that shown in Figure 1 in that the shroud 20 is secured to the aerosol can 4 by reducing the diameter of the sidewall 20 of the shroud in the region 30 such that it forms an interference fit with the aerosol can 4.
- the diameter reduction may be achieved by means of a recone punch and die.
- the shrouded can may then be used in the identical manner to that described with reference to Figure 1.
- An advantage of the embodiments of the invention over that of plastic shrouds of the prior art is that a greater force is needed to separate the shroud from the can, even further limiting the possibility of them becoming separated during or after manufacture.
- a particular advantage of the embodiment shown in Figure 2 is that it is possible to make a water-tight seal between the shroud and the can in the region 30, so that water does not enter the space between the shroud and can during waterbath testing of the filled can.
- FIG. 3 represents an exploded view of a further embodiment in accordance with the invention.
- the shroud 20 is in the form of an aerosol can of larger size to the can 4 in which the aerosol formulation is contained.
- the can 4 comprises the circular base 6 and a cylindrical sidewall 8 extending from the base to an open end 32.
- the open end 32 comprises a circumferential flange 34 which is dimensioned to extend over the neck 21 of the larger aerosol can which is the shroud 20.
- the valve ferrule 18 is crimped over the neck 21 trapping the circumferential flange 34 between the ferrule and the neck thereby firmly securing the aerosol can 4 within the shroud 20.
- the gasket seal 19 of the aerosol valve forms a seal with the circumferential flange 34.
- This embodiment has the advantage that it is compatible with the existing assembly and filling equipment and that the post-manufacture handling and uses e.g. function testing, labelling etc. remain unchanged. Furthermore, the design is tamper proof and it is not apparent to the patient that there is a smaller container within the shroud.
Landscapes
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dispersion Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Anesthesiology (AREA)
- Chemical & Material Sciences (AREA)
- Mechanical Engineering (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
- Medicinal Preparation (AREA)
Abstract
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0101239A GB0101239D0 (en) | 2001-01-17 | 2001-01-17 | Medicinal aerosols |
GB0101239 | 2001-01-17 | ||
GB0120658 | 2001-08-24 | ||
GB0120658A GB0120658D0 (en) | 2001-01-17 | 2001-08-24 | Medical aerosols |
PCT/US2002/001502 WO2002056949A1 (fr) | 2001-01-17 | 2002-01-16 | Aerosols a usage medicinal |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1357964A1 true EP1357964A1 (fr) | 2003-11-05 |
Family
ID=26245577
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP02702021A Withdrawn EP1357964A1 (fr) | 2001-01-17 | 2002-01-16 | Aerosols a usage medicinal |
Country Status (2)
Country | Link |
---|---|
EP (1) | EP1357964A1 (fr) |
WO (1) | WO2002056949A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2525226A (en) * | 2014-04-16 | 2015-10-21 | Presspart Mfg Ltd | Metered dose inhaler canister and shroud |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE202004007115U1 (de) * | 2004-05-03 | 2004-07-08 | Altana Pharma Ag | Blindungsvorrichtung |
GB0518400D0 (en) | 2005-09-09 | 2005-10-19 | Clinical Designs Ltd | Dispenser |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2912670A1 (de) * | 1979-03-30 | 1980-10-09 | Lechner Gmbh | Zweikammer-druckdose zur abgabe eines fuellgutes |
FR2545792B1 (fr) * | 1983-05-13 | 1985-09-06 | Avitex | Emballage du type aerosol bicameral |
GB8919131D0 (en) * | 1989-08-23 | 1989-10-04 | Riker Laboratories Inc | Inhaler |
GB2267936B (en) * | 1992-06-09 | 1996-01-31 | Minnesota Mining & Mfg | Aerosol vial |
WO1999016684A1 (fr) * | 1997-10-01 | 1999-04-08 | Osaka Shipbuilding Co., Ltd. | Contenant sous pression double conçu pour charger une sous-cupule et produits sous pression doubles utilisant ce contenant |
-
2002
- 2002-01-16 EP EP02702021A patent/EP1357964A1/fr not_active Withdrawn
- 2002-01-16 WO PCT/US2002/001502 patent/WO2002056949A1/fr not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO02056949A1 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2525226A (en) * | 2014-04-16 | 2015-10-21 | Presspart Mfg Ltd | Metered dose inhaler canister and shroud |
GB2525226B (en) * | 2014-04-16 | 2020-07-29 | Presspart Mfg Ltd | Metered dose inhaler canister and shroud |
Also Published As
Publication number | Publication date |
---|---|
WO2002056949A1 (fr) | 2002-07-25 |
WO2002056949A8 (fr) | 2003-12-18 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
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17P | Request for examination filed |
Effective date: 20030814 |
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AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
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AX | Request for extension of the european patent |
Extension state: AL LT LV MK RO SI |
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17Q | First examination report despatched |
Effective date: 20060801 |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: B65D 83/14 20060101ALI20081204BHEP Ipc: A61M 15/00 20060101AFI20081204BHEP |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: B65D 83/14 20060101ALI20081205BHEP Ipc: A61M 15/00 20060101AFI20081205BHEP |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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18D | Application deemed to be withdrawn |
Effective date: 20090609 |