CA1270711A - Inhaler - Google Patents
InhalerInfo
- Publication number
- CA1270711A CA1270711A CA000515100A CA515100A CA1270711A CA 1270711 A CA1270711 A CA 1270711A CA 000515100 A CA000515100 A CA 000515100A CA 515100 A CA515100 A CA 515100A CA 1270711 A CA1270711 A CA 1270711A
- Authority
- CA
- Canada
- Prior art keywords
- air
- ball
- path
- inhaler according
- support
- 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.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
-
- 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
- A61M15/0001—Details of inhalators; Constructional features thereof
- A61M15/0005—Details of inhalators; Constructional features thereof with means for agitating the medicament
- A61M15/0006—Details of inhalators; Constructional features thereof with means for agitating the medicament using rotating means
- A61M15/0008—Details of inhalators; Constructional features thereof with means for agitating the medicament using rotating means rotating by airflow
-
- 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
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/06—Solids
- A61M2202/064—Powder
-
- 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
- A61M2206/00—Characteristics of a physical parameter; associated device therefor
- A61M2206/10—Flow characteristics
- A61M2206/16—Rotating swirling helical flow, e.g. by tangential inflows
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- External Artificial Organs (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Weting (AREA)
- Luminescent Compositions (AREA)
- Organic Insulating Materials (AREA)
- Polyoxymethylene Polymers And Polymers With Carbon-To-Carbon Bonds (AREA)
Abstract
ABSTRACT
An inhaler is described for introducing a solid substance in particulate form into the inhaled air of a user. The inhaler comprises a body in which is provided an endless orbital path for one or more balls. Air enters the path via an air inlet, optionally through an intake conduit. Air leaves the orbital path in a centripetal direction through an air discharge system and an air outlet. The solid substance to be inhaled is provided, preferably in the form of a film, on the surface of the orbital path or on the surface of the ball. A user inhales through the air outlet, and this causes air to be drawn into the orbital path through the air inlet. This causes the ball to circulate around the orbital path, in which process solid substance is dislodged and caused to flow with the air out through the outlet.
An inhaler is described for introducing a solid substance in particulate form into the inhaled air of a user. The inhaler comprises a body in which is provided an endless orbital path for one or more balls. Air enters the path via an air inlet, optionally through an intake conduit. Air leaves the orbital path in a centripetal direction through an air discharge system and an air outlet. The solid substance to be inhaled is provided, preferably in the form of a film, on the surface of the orbital path or on the surface of the ball. A user inhales through the air outlet, and this causes air to be drawn into the orbital path through the air inlet. This causes the ball to circulate around the orbital path, in which process solid substance is dislodged and caused to flow with the air out through the outlet.
Description
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Inhaler ~ his invention relates to an inhaler by means of which a solid substance in particulate form, in particular a pharmacologically active substance, can be introduced into the inhaled air of the user of the inhaler.
Various types of such inhaler are known, one of which is disclosed in German Patent 845~85 (and equivalent U.K. Patent 654860) granted to Abbott Laboratories. In the Abbott device a supply of solid material in the form of a fine powder is provided in a capsule having a mesh screen at the lower end. ~he capsule is adapted to be inserted into -the device in such a manner that its lower part projects into a chamber communica-ting with an air inlet via an inlet tube bent to form appro~imately a semicircle. An air outlet is provided in the form of a mouthpiece or the like. A ball is located in the inlet tube and is moved duringinhalation by the flow of the inhaled air towards the end of the lnlet tube~ whereby the ball strikes against the capsule and causes a small amount of solid material to fall through the screen of the capsule and to enter the airstream.
A major drawback of the device iUSt described is that it is suitable only for dispensing a relatively . . ~, .: . . ...; . .
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large quantity of material, which means that the material in the capsule has to comprise a large amount of an inert carrier in addition to the active substance.
~his means that it requires many inhalations to transport such an amount of solid material, and it may take from 5 to 10 minutes for a user to inhale sufficient air to take in the required dose of the active substance.
~his is unacceptable in many cases, particularly where inhalation is intended to relieve conditions which require immediate treatment, such as the conditions pre-vailing in an asthmatic attack.
Furthermorej because of its shape; the device described above is rather unwieldy and is too large to be conveniently carried around in a bag or pocket. Finally, too much handling is required on the part of the user to prepare for use, i.e. insertion of the capsule into the device after removal of a cap sealing the screen (at wh~ch point there is a tlnager of loss of solids through the screen) and the need for correct positioning of the device during inhalation.
It should be mentioned at this point that somej though not all, of the disadvantages referred to above are shared by other forms of known inhaler. In particularj all inhalers presently on the market are relatively large in size andj as a consequence of their expensej all are intended for repeated use.
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3 200~5-115 It is an object of the present inven-tion to provide an inhaler of a design which is such that, if desired, it can be made much smaller than known inhalers and which is sufficiently simple and inexpensive that it may be used only once and then disposed of, and also to provide a device by means of which a uniform and reproducible dose may be dispensed.
According to the present invention ~here is provided an inhaler for introducing a solid substance in particulate form into the inhaled air of a user, comprising (a) a body having (l) an internal surface deining an endless path, (2) an intake conduit for the inhaled air, the air intake conduit opening tangentially into said endless path, and (3) an air outlet adapted for fluid communication with a breathing passage of the user and discharge means for the inhaled air in fluid communication with said endless path and the air outlet, and said air outlet and discha~ge means being disposed centripetally relative to the endle~s path whereby inhalation by the user through the ouklet causes air to 1OW
through the air intake conduit, the endless path and the discharge means to the out]etl (b) a ball having a surface and being disposed in said end]ess path, the ball being arranged in said endless path to circulate therearound under the effect of the air flow, and (c) a solid medicament substance distributed between the surface of the endless path and the ball.
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-~- 20~85-115 ~ ention will now be made of the principLes of operation of the device, as they are presently understood. It is to be appreciated, however, that the operation of the device is in no way dependent on the correctness of the explanation now put forward. Air is caused to enter the orbital path, preferably tangentially, by suction applied at the air outlet. This sets the ball in orbital motion, which movement of the ball gives rise to a spectrum of relative movements between the stationary surface of the orbital path and the surface of the ball rotating in every direction in space. These relative movements exert , ~
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compressive and shear forces on the material on the ball surface, on the surface of the orbital path, or between the surfaces o~ the ball and the orbital pathj which initiates a fragmentation process.
- rhis is combined with a process of aerosol formation, whereby finely ground particulate material is dispersed into the air that leaves the orbital path via the air outletj preferably centripetally.
It is convenient at this point to note the advantageous effect provided by having the outlet air flowing centripetally. Both the ball and particulate material circulating around the orbital path are subjected to centrifugal forces, whereas the air is forced to leave the path cen-tripetally. ~his produces a rnixing effect between the air and the part3cles, with the air inevitably carrying with it a certain proportion of the solid particles. It is further to be noted that the opposing centrifugal and centripetal forces acting on the particles give rise to a d~stinction between smaller and larger particlesj wlth the smaller particles being more likely to be entrained by the air to flow centripetallyj and the larger particles being less likely to be entrained. ~he larger p~rticles thus tend to remain in the orbital path until they are reduced to a smaller size. A further, and quite distinct advantage of having outlet air flowing ; ' ' ~ .
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centripetally is that this tends to reduce the size of device and makesit easier to construct.
~ he inhaler according to the present inven-tion permits small amount of active substances to be administered in accurate doses. It should therefore be unnecessary to dilute the active substance and thus rapid action can be achieved in a short'time'period.
' ~he device does not require a separate cartridge or other container for the active substancej nor does it re~uire specific positioning when in use which makes it simple and safe to handle. Due to its almost immediate action it is suitable for use in emergency situations. ~he device can be simply constructed at low cost, which permits it to be used once and then'disposed of.
Furthermorej the design of the inhaler allows production in a very small size, so that the inhaler may conveniently be carried by a user at any -time.
Instead of one ball, two, three or even more balls may be provided in the orbital path. ~dditional balls provide additional areas of friction, thus improving th~ discharge of solids. ~his effect can be further enhanced if the balls have different ~5 diameters.
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~ he diameter of the ball used is preferably from
Inhaler ~ his invention relates to an inhaler by means of which a solid substance in particulate form, in particular a pharmacologically active substance, can be introduced into the inhaled air of the user of the inhaler.
Various types of such inhaler are known, one of which is disclosed in German Patent 845~85 (and equivalent U.K. Patent 654860) granted to Abbott Laboratories. In the Abbott device a supply of solid material in the form of a fine powder is provided in a capsule having a mesh screen at the lower end. ~he capsule is adapted to be inserted into -the device in such a manner that its lower part projects into a chamber communica-ting with an air inlet via an inlet tube bent to form appro~imately a semicircle. An air outlet is provided in the form of a mouthpiece or the like. A ball is located in the inlet tube and is moved duringinhalation by the flow of the inhaled air towards the end of the lnlet tube~ whereby the ball strikes against the capsule and causes a small amount of solid material to fall through the screen of the capsule and to enter the airstream.
A major drawback of the device iUSt described is that it is suitable only for dispensing a relatively . . ~, .: . . ...; . .
. ,: - - ~ . .
;,, ~7C~7~
large quantity of material, which means that the material in the capsule has to comprise a large amount of an inert carrier in addition to the active substance.
~his means that it requires many inhalations to transport such an amount of solid material, and it may take from 5 to 10 minutes for a user to inhale sufficient air to take in the required dose of the active substance.
~his is unacceptable in many cases, particularly where inhalation is intended to relieve conditions which require immediate treatment, such as the conditions pre-vailing in an asthmatic attack.
Furthermorej because of its shape; the device described above is rather unwieldy and is too large to be conveniently carried around in a bag or pocket. Finally, too much handling is required on the part of the user to prepare for use, i.e. insertion of the capsule into the device after removal of a cap sealing the screen (at wh~ch point there is a tlnager of loss of solids through the screen) and the need for correct positioning of the device during inhalation.
It should be mentioned at this point that somej though not all, of the disadvantages referred to above are shared by other forms of known inhaler. In particularj all inhalers presently on the market are relatively large in size andj as a consequence of their expensej all are intended for repeated use.
- .
.:,.: : .:, . :, ...:
. :.. , : . :
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3 200~5-115 It is an object of the present inven-tion to provide an inhaler of a design which is such that, if desired, it can be made much smaller than known inhalers and which is sufficiently simple and inexpensive that it may be used only once and then disposed of, and also to provide a device by means of which a uniform and reproducible dose may be dispensed.
According to the present invention ~here is provided an inhaler for introducing a solid substance in particulate form into the inhaled air of a user, comprising (a) a body having (l) an internal surface deining an endless path, (2) an intake conduit for the inhaled air, the air intake conduit opening tangentially into said endless path, and (3) an air outlet adapted for fluid communication with a breathing passage of the user and discharge means for the inhaled air in fluid communication with said endless path and the air outlet, and said air outlet and discha~ge means being disposed centripetally relative to the endle~s path whereby inhalation by the user through the ouklet causes air to 1OW
through the air intake conduit, the endless path and the discharge means to the out]etl (b) a ball having a surface and being disposed in said end]ess path, the ball being arranged in said endless path to circulate therearound under the effect of the air flow, and (c) a solid medicament substance distributed between the surface of the endless path and the ball.
. .
.: : : :: : :
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7 ~
-~- 20~85-115 ~ ention will now be made of the principLes of operation of the device, as they are presently understood. It is to be appreciated, however, that the operation of the device is in no way dependent on the correctness of the explanation now put forward. Air is caused to enter the orbital path, preferably tangentially, by suction applied at the air outlet. This sets the ball in orbital motion, which movement of the ball gives rise to a spectrum of relative movements between the stationary surface of the orbital path and the surface of the ball rotating in every direction in space. These relative movements exert , ~
. ' ': , ~7~
compressive and shear forces on the material on the ball surface, on the surface of the orbital path, or between the surfaces o~ the ball and the orbital pathj which initiates a fragmentation process.
- rhis is combined with a process of aerosol formation, whereby finely ground particulate material is dispersed into the air that leaves the orbital path via the air outletj preferably centripetally.
It is convenient at this point to note the advantageous effect provided by having the outlet air flowing centripetally. Both the ball and particulate material circulating around the orbital path are subjected to centrifugal forces, whereas the air is forced to leave the path cen-tripetally. ~his produces a rnixing effect between the air and the part3cles, with the air inevitably carrying with it a certain proportion of the solid particles. It is further to be noted that the opposing centrifugal and centripetal forces acting on the particles give rise to a d~stinction between smaller and larger particlesj wlth the smaller particles being more likely to be entrained by the air to flow centripetallyj and the larger particles being less likely to be entrained. ~he larger p~rticles thus tend to remain in the orbital path until they are reduced to a smaller size. A further, and quite distinct advantage of having outlet air flowing ; ' ' ~ .
~ ~ i ...
' ' ` .
~L~ o'~
centripetally is that this tends to reduce the size of device and makesit easier to construct.
~ he inhaler according to the present inven-tion permits small amount of active substances to be administered in accurate doses. It should therefore be unnecessary to dilute the active substance and thus rapid action can be achieved in a short'time'period.
' ~he device does not require a separate cartridge or other container for the active substancej nor does it re~uire specific positioning when in use which makes it simple and safe to handle. Due to its almost immediate action it is suitable for use in emergency situations. ~he device can be simply constructed at low cost, which permits it to be used once and then'disposed of.
Furthermorej the design of the inhaler allows production in a very small size, so that the inhaler may conveniently be carried by a user at any -time.
Instead of one ball, two, three or even more balls may be provided in the orbital path. ~dditional balls provide additional areas of friction, thus improving th~ discharge of solids. ~his effect can be further enhanced if the balls have different ~5 diameters.
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~ he diameter of the ball used is preferably from
2 to 7 mmj more preferably 3 to 5 mm, and most preferably about 4 mm. Where a plurality of balls is used the above diameter refers to the diameter of the larger or largest of thc balls.
~ he solid material which is to be inhaled is preferably applied in the form of a film onto the surface of the ball and/or the surface of the orbital path. ~he surface of the ball and/or the surface of the orbital path are preferably not smooth as this provides for a larger quantity of substance to be applieflj a simpler application of the substance more rapid fragmentation of the film during use of the device, and better dispersion of the substance in the air during use.
In a preferred embodiment the body of the inhaler consists of a support in which are formed the orbital pathj the tangential alr intake conduit, (if one is provided) and an air discharge system which is centripetal relative to the orbital pathj and a cover-sheet provided with the air inlet and the air outlet. In this embodiment the air inlet and the air outlet are preferably formed as simple, circular air passage openings in the cover sheet. In order to ensure conditions of low cicrobiolo~ical cont~mination up to the ti~et~i~en the device is used, the cover sheet is preferably itself covered by a pull-off film which closes the air inlet ., ~
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and air outle-t. In order to prevent the film from re-taining particles of solid material in the area of the lnlet and outlet of the cover sheet, whlch particles may have come off the surfaces of the ball or orbital path during transport or handlingj the film is preferably designed to be repellent to such particles in the area of the air inlet and outlet. For tha-t purpose the film may be coated metal, preferably coated aluminium, with the coating on the side facing the air inlet and outlet.
Alternatively, the film may be a wholly metal film, for example an aluminium film, or it may be a laminated film for example composed of laminated films of paper and aluminium, or a film coated with a hydrophobic material such as polytetrafluoroethylene.
~he invention will now be further described with reference -to the accompanying drawingsj in which:
Figure 1 is a diagrammatic representation in sectional elevation of a first embodiment of the device according to the inven-tionj the body of which is composed 2~ of a suppor-t and a cover-sheet;
Figures 2 and 3 are top plan vie~sof -the support and cover-sheet of the device shown in Figure lj F:Lgure 4 is an enlarged section along the line IV-IV of Figure 2:
Figure 5 is a sectional elevation, in exploded .. . ...
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formj of a second embodiment of the device according to the invention;
Figures 6 and 7 are top plan views of the support and the cover-sheet of the device according to Figure 5;
Figure 8 is a diagra~natic sectional view of a prototype of the device according to the invention produced for text purposes and having an exchangeable insert body;
Figures 9 and 10 show the insert body of Figure 8 in elevation and top view respectively;
Figures 11 and 12 are diagrams of two possible ; configurations of the orbital path of the inhaler deviating from a circular form;
Figure 13 is a perspective view of another embodiment having a mouthpiece; and Figure 14 is a top plan view o~ the support and cover-sheet of a further ei.lhodiment of the invention.
rhe inhaler illus-trated in Figures l to 3 has a body composed of a support 1 and a cover-sheet 2j the support 1 having a recess which defines in the body a toroidalj circular orbital path 3 for a ball 4. ~he support 1 has a further recess which defines an air intake conduit 5 opening into -the orbital path 3. rhe conduit 5 communicates with a circular air passage opening 6 in the cover-sheet 2j which opening constitutes the air inlet o~ the ~ .
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device. ~he support 1 is further provided with an air discharge system 7 which provides communication between the orbital path 3 and a circular air passage opening 8 formed in the cover-sheet 2 and constituting the air outlet of the inhaler. A pull-off film 9 seals the inlet and outlet openings 6 and 8 in a sterile manner. It will be noted that the air intake conduit 5 is of smaller depth than the orbital path
~ he solid material which is to be inhaled is preferably applied in the form of a film onto the surface of the ball and/or the surface of the orbital path. ~he surface of the ball and/or the surface of the orbital path are preferably not smooth as this provides for a larger quantity of substance to be applieflj a simpler application of the substance more rapid fragmentation of the film during use of the device, and better dispersion of the substance in the air during use.
In a preferred embodiment the body of the inhaler consists of a support in which are formed the orbital pathj the tangential alr intake conduit, (if one is provided) and an air discharge system which is centripetal relative to the orbital pathj and a cover-sheet provided with the air inlet and the air outlet. In this embodiment the air inlet and the air outlet are preferably formed as simple, circular air passage openings in the cover sheet. In order to ensure conditions of low cicrobiolo~ical cont~mination up to the ti~et~i~en the device is used, the cover sheet is preferably itself covered by a pull-off film which closes the air inlet ., ~
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and air outle-t. In order to prevent the film from re-taining particles of solid material in the area of the lnlet and outlet of the cover sheet, whlch particles may have come off the surfaces of the ball or orbital path during transport or handlingj the film is preferably designed to be repellent to such particles in the area of the air inlet and outlet. For tha-t purpose the film may be coated metal, preferably coated aluminium, with the coating on the side facing the air inlet and outlet.
Alternatively, the film may be a wholly metal film, for example an aluminium film, or it may be a laminated film for example composed of laminated films of paper and aluminium, or a film coated with a hydrophobic material such as polytetrafluoroethylene.
~he invention will now be further described with reference -to the accompanying drawingsj in which:
Figure 1 is a diagrammatic representation in sectional elevation of a first embodiment of the device according to the inven-tionj the body of which is composed 2~ of a suppor-t and a cover-sheet;
Figures 2 and 3 are top plan vie~sof -the support and cover-sheet of the device shown in Figure lj F:Lgure 4 is an enlarged section along the line IV-IV of Figure 2:
Figure 5 is a sectional elevation, in exploded .. . ...
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formj of a second embodiment of the device according to the invention;
Figures 6 and 7 are top plan views of the support and the cover-sheet of the device according to Figure 5;
Figure 8 is a diagra~natic sectional view of a prototype of the device according to the invention produced for text purposes and having an exchangeable insert body;
Figures 9 and 10 show the insert body of Figure 8 in elevation and top view respectively;
Figures 11 and 12 are diagrams of two possible ; configurations of the orbital path of the inhaler deviating from a circular form;
Figure 13 is a perspective view of another embodiment having a mouthpiece; and Figure 14 is a top plan view o~ the support and cover-sheet of a further ei.lhodiment of the invention.
rhe inhaler illus-trated in Figures l to 3 has a body composed of a support 1 and a cover-sheet 2j the support 1 having a recess which defines in the body a toroidalj circular orbital path 3 for a ball 4. ~he support 1 has a further recess which defines an air intake conduit 5 opening into -the orbital path 3. rhe conduit 5 communicates with a circular air passage opening 6 in the cover-sheet 2j which opening constitutes the air inlet o~ the ~ .
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device. ~he support 1 is further provided with an air discharge system 7 which provides communication between the orbital path 3 and a circular air passage opening 8 formed in the cover-sheet 2 and constituting the air outlet of the inhaler. A pull-off film 9 seals the inlet and outlet openings 6 and 8 in a sterile manner. It will be noted that the air intake conduit 5 is of smaller depth than the orbital path
3 so that the ball 4 is provided with sufficien-t mechanical guidance even in the area adjacent -the opening of the conduit into the path. ~he active substance to be inhaled is preferably applied in the form of a film to the surface of the ball ~ and/or the surface of the orbital path 3 in a manner described in more detail below.
As shown in Figure 4j the ball has a certain arnount of play with respect to the surface o~ the path 3j this surface being provided partly by the inner surface of the support 1 and partly by a portion of the inner surface of cover-sheet 2. ~he amount of play deterrnines the efficiency of the air propulsion of the ball and the extent to which the active substance is taken up by air leaving the orbital path.
Due to suction of air occurring during inha]ation at the air outlet 8j air enters the orbital path through the intake conduit S and propels the ball 4. As . .
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already indicatedj because of the movement of the ballj compressive and shear forces are exerted between the surface of the ball and the surface of -the orbital pa-thj which serve in the first instance to remove particles of active substance from whichever of those surfaces it has been applied toj and then serve to grind or disperse those particles.
~ he fine particles are thereby distributed in the air that leaves the orbital path through the discharge system 7 and thence through the air outlet 8 to the user.
~ he centripetal air discharge system 7 is formed by the free space between the support 1 and the cover-sheet 2 in a central area 10 defined within the orbital path 3. In the embodiment of Eigures 1 to ~ the air discharge system 7 is simply an annular clearance of uniform ¢ross-section, the external diameter o~ which is the diameter D of the area 10 and the internal diameter of which is the diameter of the circular air outlet ~.
Efficiency in propulsion of the ball can be improved by giving the above mentioned annular clearance a non-uniform cross-section, such that the cross-section is a minimum immediately after entry of the intake conduit 5 into the orbital path (location a in Figure 2) and increases steadily to reach a .
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maximum immediately before the air intake conduit (location b in Figure 2), before returning abruptly to a minimum (at location c in Figure 2). Such a variation in the cross-section of the air discharge system 7 can be easily obtained by a spiral or serrated configuration of the central area lO of the orbital path 3j as is explained below in more detail with reference to Figures 8 to lO.
In the embodiment illustrated in Figures 5 to 7, the central area lO has an upper frusto-conical portion with a cone angle of 120. ~he upper surface of the frusto-conical portion is co-planar with the upper surface of the interface between the support 1 and the cover-sheet 2. ~he air outlet 8 has a diameter corresponding to the inner diameter of the orbital path 3, i.e. the diameter of the base of the frusto-conical portion of the cen-tral area lOj so as to form an annular clearance between the lower edge of the air outlet 8 of the cover-sheet 2 and the frusto-conical surface of the central area lO. As in the case of the embodiment of Figures 1 to 4 the air discharge system is provided by an annular clearance which is rotationally symmetricalj i.e.
the annular clearance has the same cross-section at all points.
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In a typical practical embodiment of the device shown in Figures 5 to 7j the length of the inhaler is 50 mmj the width 22 mm and the height 4.5 mm, ~he orbital path has a width of 3.1 mm and the glass ball used has a diameter of 3 mm. ~he diameter of -the air outlet opening 8 is 10 m~, and the diameter of the air inlet opening 6 is 5 mm. Dependi~g on the chosen pressure difference and the ball tolerance selectedj the rotational speed of the ball is between 5 and 5~ Hz, which corresponds to 300 to 3000 revolutions per minute. If, as is preferredj the ball diameter is
As shown in Figure 4j the ball has a certain arnount of play with respect to the surface o~ the path 3j this surface being provided partly by the inner surface of the support 1 and partly by a portion of the inner surface of cover-sheet 2. ~he amount of play deterrnines the efficiency of the air propulsion of the ball and the extent to which the active substance is taken up by air leaving the orbital path.
Due to suction of air occurring during inha]ation at the air outlet 8j air enters the orbital path through the intake conduit S and propels the ball 4. As . .
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already indicatedj because of the movement of the ballj compressive and shear forces are exerted between the surface of the ball and the surface of -the orbital pa-thj which serve in the first instance to remove particles of active substance from whichever of those surfaces it has been applied toj and then serve to grind or disperse those particles.
~ he fine particles are thereby distributed in the air that leaves the orbital path through the discharge system 7 and thence through the air outlet 8 to the user.
~ he centripetal air discharge system 7 is formed by the free space between the support 1 and the cover-sheet 2 in a central area 10 defined within the orbital path 3. In the embodiment of Eigures 1 to ~ the air discharge system 7 is simply an annular clearance of uniform ¢ross-section, the external diameter o~ which is the diameter D of the area 10 and the internal diameter of which is the diameter of the circular air outlet ~.
Efficiency in propulsion of the ball can be improved by giving the above mentioned annular clearance a non-uniform cross-section, such that the cross-section is a minimum immediately after entry of the intake conduit 5 into the orbital path (location a in Figure 2) and increases steadily to reach a .
....
.
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maximum immediately before the air intake conduit (location b in Figure 2), before returning abruptly to a minimum (at location c in Figure 2). Such a variation in the cross-section of the air discharge system 7 can be easily obtained by a spiral or serrated configuration of the central area lO of the orbital path 3j as is explained below in more detail with reference to Figures 8 to lO.
In the embodiment illustrated in Figures 5 to 7, the central area lO has an upper frusto-conical portion with a cone angle of 120. ~he upper surface of the frusto-conical portion is co-planar with the upper surface of the interface between the support 1 and the cover-sheet 2. ~he air outlet 8 has a diameter corresponding to the inner diameter of the orbital path 3, i.e. the diameter of the base of the frusto-conical portion of the cen-tral area lOj so as to form an annular clearance between the lower edge of the air outlet 8 of the cover-sheet 2 and the frusto-conical surface of the central area lO. As in the case of the embodiment of Figures 1 to 4 the air discharge system is provided by an annular clearance which is rotationally symmetricalj i.e.
the annular clearance has the same cross-section at all points.
: :,. .:
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In a typical practical embodiment of the device shown in Figures 5 to 7j the length of the inhaler is 50 mmj the width 22 mm and the height 4.5 mm, ~he orbital path has a width of 3.1 mm and the glass ball used has a diameter of 3 mm. ~he diameter of -the air outlet opening 8 is 10 m~, and the diameter of the air inlet opening 6 is 5 mm. Dependi~g on the chosen pressure difference and the ball tolerance selectedj the rotational speed of the ball is between 5 and 5~ Hz, which corresponds to 300 to 3000 revolutions per minute. If, as is preferredj the ball diameter is
4 mm the width of the orbital path is preferably about 4,3 mmj with the other dimensions already mentioned being substantially the same. ~he same dimensional characteristics apply, in substancej -to the embodiment of ~igures 1 to 4.
It wil]. be seen from the above discussion of dimensions that the device of the present invention can indeed be made extremely smallj in contrast to presently available inhalers.
Figure 8 shows part of a prototype of the inhaler according to the inventionj composed of three aluminium elements. ~he three elements are a lower support body la with a circular orbltal path 3a, an upper cover-plate 2a with a circular air passage 8a forming the air outlet and an exchangeable insert body , 7~L
llj the top lla of which constitutes the central area of the orbital path 3a. ~his prototype has been used to test various geometrical configurations of the central area of the orbital path.
As can be seen in Figure ~, the frusto-conical path llb of top lla of the insert body 11 has a spiral formj by virtue of which the cross-section of the annular clearance 7a forming the centripetal air discharge system widens from a minimum immediately after the junction with the air intake conduit up to a maximum immediately before the air intake conduit.
With reference to Figures 9 and 10, which show the insert body in elevation and top viewj a brief description will now be given of t,he production of the spira:L form mentioned above by means of an end-milling cutter. l'he insert body 11 s-tarts with the shape illustrated in the upper portion of Figure 9, that is to sayj the top has a lower cylindrical portion surmounted by a frusto-conical portion having a cone angle of 90. ~he insert body 11 is then slowly turned about its vertical axis and at the same time a milling cutter is slowly advanced towards -the a~is of rotation of the insert body. ~he milling cutter is a tool approximately 4 to 5 mm in diameterj and the axis of rotation of the milling cutter is denoted ~27~37~
by reference numeral 12 in Figure 9. ~he insert body 11 is rotated through an angle of 330 while the milling cutter advances, and this produces the spiral form shown in Figures 8 to 10.
As a result of the spiral form of the central area of the orbital pathj the cross-section of the air discharge annular clearance is relatively small in the first propulsion phase of the ball, a phase which can be regarded as extending for about 120 from immediately after the opening of the air intal~e conduit into the orbital path. During this phase little air can flow out of the orbital path. ~here-after a second phase ensues during which the cross-section of the clearance becomes progressively wider so that more and more air can be discharged from the annular path. It will be appreciated that there is no definite division between the two phases, since the increase in t~e width of the annular clearance is continuous. During the first phase effective propulsion of the ball is achievedj the aim being to get as high a rotational speed for the ball as possible. During the second phase the ball continues to be propelled ; but larger amounts of air are lost from the region ahead of the ball, the alr taking with it particulate material to be inhaled. ~he second phase ensures that - . ....
. .. .~" .;.
the desired amount of parti.culate material can be inhaled at an acceptably low suction pressure.
It has been found that an orbital path deviating slightly from a circular form may be useful, since periodic acceleration effects on the ball tend to result in improved removal of active substance from the surface of the ball and/or the surface o~ the orbital path, and in improved aerosol formation. Such periodic acceleration forces may be brought about by using an elliptical pathj or by using a generally circular path with a plurality of convex or concave indenta-tionsj for example from two to four such indentations. In either case, deviations from the circular form should not be too great or else the braking ef:eect on the ball will become too large.
With elliptical paths an ellipticity coefficient of about 1.25 has proved to be suitable.
Fi~ures 11 and 12 are diagrams illustrating two examples of circular paths with convex and concave indentations respectively. Arrow 13 indicates the direction of air intake into the orbital path. ~he deviation from the circular form marked with d may amount to about 1/25 of the diame-ter of the circular path.
l'he device according to the present invention , may be used for inhala-tion either through the mouth or through the nose. In order to make the device easier to use an outlet member in the form of a mouthpiece or nose-piece, as the case may requirej may be mounted on the cover sheet 2 to communicate with the air outlet opening 8. Fig-ure 13 is a perspective view of a device according to the invention having a mouthpiece; which is denoted by reference numeral 20. In other respects the device of Figure 13 is broadly the same as that of ~igures 5 to 7j and the same reference numerals are therefore used in Figure 13 as in those Figures.
~ he provision of such an outlet member becomes parti-cularly valuable in connection with the further embodiment of the inven-tion which is shown in Figure 14~ In the em-bodiment of Figure 14 the intake conduit 5 is omitted andair enters the orbital path 3 through an air inlet 6' pro-vided in the supportl' rather than the cover-sheet 2'. rhe cover-~heet 2' contains only the air outlet 8. Both the support 1' and the cover-sheet 2' are reduced in siæe com-pared to the previously described embodirnentsj and are shown in Figure 14 as being circular in form. rhis em-bodiment is so small that it is very desirable to include an outlet member in the form of a mouthpiece or nosepiece to enable the device to be conveniently handled by a user.
~he body of the inhaler according to the present in-ventionj i.e. the support 1 or 1' and cover-sheet 2 or 2' may suitably be made of a plas-tics materialj for example ABSj the support being either an injection-moulded part formed from a plastics granulatej or a : , :
.
: .-.,.' "''; ' ~
1~707~
deep-drawn moulding formed of plastics sheeting which is heated and formed over a mould. Injection-moulding is presently preferred since that process allows for higher precision. Alternatively, the body of the inhaler may be formed from a metal, such as aluminium, the desired form being achieved by stamping or by deep-drawing.
~ he support and cover-sheet may be joined by a variety of methods, depending on the materials involved, including ultrasonic weldingj anodic bonding, or adhesion. If adhesion is used the amount of adhesive the pattern in which adhesive is applied and the contact pressure used must be such that penetration of the adhesive into the path of the ball is avoided.
~he ball may be made of glassj metal, a plastics materialj a ceramic material, for e~ample alumina.
For reasons already mentionedj it is preferred that the surface of the ball and/or the surface of the orbital pathj should be non-smooth. In the case of glass ballsj a rough ground surface gives the desired effectj and permits good adhesion of the active substance when applied thereto byj wetting with a solution of the active substance and subsequent evaporation of the solvent. ~he manner of applying the active substance to the glass balls is described in more detail below. Alternativelyj the ball may have .
~'~7~
a surface structure similar to that of a golf ball.
If the surface of the orbital path is non-smoothj and possiblyj the active substance applied also to the orbital pathj the glass ball used may be acid-treated.
In addition to any surface characteristicswhich the surface of the orbital path may have to render it non-smoothj the orbital path surface preferably has helical grooves formed therein e~tending along the direction of movement of the ballj similar to the ri~lings in firearms. Contact of the ball with the grooved helical path causes the ball to spin perpendicular to the direction of travel. ~his is believed to be of particular advantage in relation to the dispersion of the active substance in -the air.
~he helical grooves may be formed in the orbital path during the injection-mouldingjdeep-drawingj stamping or other process by which the support is formed.
~he grinding and dispersing ~unctions of the ball will become clearer on considering the dynamic behaviour of the travelling ball with reference to ~igure ~.
1. Under the influence of centrifugal force~the ball is in rolling contact with the outer annular wall :
,. :~
~7~37~L~
of orbital path 3 (see point of contact B). ~his causes turning of the ball about a~is A.
2. Helical grooving of the surface of the orbital path causes simultaneous turning of the ballj e~g.
in the direction of the arrow, about axis C, which extends perpendicularly to the plane of the drawing.
3. ~he speed gradient between the surface for the ball and the surface of the orbital path continues to increase in the direction of arrows Lj which represent the airflow towards the centripetal discharge system whichj due to the acceleration forces on the particles, contributes to good particle~
air distribution.
rhe i.nhaler according to the invention is suitable for the administration of any pharmacologically active substance that can be inhaled and is absorbed via the mucous membranes of the respiratory passages.
In particular, the inhaler is designed for the treatment of asthma and bronchitis by means of the substances salbutamolj beclomethasone dipropionate, terbutaline and sodium cromoglycate.
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~ here are several ways of introducing the active substance into the inhalerj and some of these will now be mentioned.
1. ~he active substance is dissolved in a solvent and the ball dipped into it. Upon evaporation of the solvent there remains a film o~ solid active substance.
2. A solution of active substance is introduced into the recess in the support which forms the orbital path. Upon drying a film of active substance remains in the recess.
3. After the complete device has been assembledj including the ballj the active substance is introduced in solution into the orbital pathj and upon evaporation a film of active sub~tance re~ains on the sur~ace O:e the orbital path and may remain also on the sur~ace o~ the ball.
4. ~he substance is introduced in solid ~orm into the device after assembly. In this case the particulate material simply lies on the surface o~ the orbital path without being attached thereto as it is when it is present as a film.
If the active substance is applied in solution and if the inhaler body is made of a plastics materialj account may need to be taken of the possibility that the - . ~
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solvent used may interact with the plastics materialj for example by dissolving out the plasticizer. If such an effect is anticipated the body of the inhaler can be subjected to a process of metal coating by vaporization to prevent it being attacked by the solvent.
Due to the rotation of the ballj the solid particles are finely ground or dispersed and have a diameter on leaving the inhaler such that a fraction of the particles in the range of 10 to 20 microns can be inhaled. ~he total quantity of active substance which needs to leave the inhaler will depend on the nature of the active substance itself and the dosage requirements.
For examplej for salbutamolj a typical dose is from 200 to 400 ~g.
As already mentioned, a single inhaler may be provided with more than one ball. For examplej where the orbital path has a width of 3.7 mm a pair of balls 3.5 and 3 mm in diameter may be usedj and where the orbital path has a width of ~.3 mm a pair of balls 4.1 mm and 3.7 mm may be used. ~hese dimensions are given by way of e~ample only~ and other dimensions could be used. In each case the larger ball is the one to which the air provides the main propulsive ~orce. ~he smaller ball being propelled mainly by impact with the larger ball. Where two .7 , .
balls are used both can carry the same active substance but an alternative possibility is that each may carry a different active substance. ~or example, it is sometimes necessary for salbutamol and beclomethasone dipropionate to be administered together, in which case one of the balls may be coated with one of these substance and the other ball may be coated with the other.
One further possibility afforded by the use of a plurality of balls is that one of the balls may consist purely of the active substance, or a mi~ture of active substance and an inert carrierj rather than having the active substance merely as a coating on an inert substrate such as glass. In this case the other ball or balls may carry active substance or may consist purely of the inert substrate in this case the ball of pure drug would no-t be the largest o~ the balls so that the main propulsive force would be applied to the other ballj or one o~ the other balls, as the case may be.
Some examples will now be given of compositions used to coat salbutamol onto glass balls by the solvent method referred to above. ~he compositions are given in terms of percentage by weight.
Composition 1 Glass balls 4 mm 59.95 Salbutamol 0.08 Ethanol 39.97 ,: :
' ' '~
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Composition 2 Glass balls 4 mm57 49 Salbutamol 0.08 Ethanol 42.43 Composition 3 Glass balls 4 mm- 59.37 Salbutamol 0.08 Polyvinylpyrrolidone 0.008 Ethanol 40.542 Compositon 4 Glass balls 4 mm98.96 Salbutamol 0.17 Ethanol 0.87 Composition 5 Glass balls 3 mm95.34 Salbutamol 0.58 Polyvinylpyrrolidone 0.58 Ethanol 3.50 Composition 6 Glass balls 4 mm82.22 Salbutamol 1.49 Polyvinylpyrrolidcne 1.49 Ethanol 14.80 Composition 7 Glass balls 4 mm53.91 Salbutamol 0.09 Ethanol 46.00 Composition 8 Glass balls 4 mm 95.71 Salbutamol 0.12 Polyvinylpyrrolidone 0.07 Ethanol 4.10 Composition 9 Glass balls 3 mm 91.95 Salbutamol 0.56 Polyvinylpyrrolidone 0.09 10 Ethanol 7.40 Composition 10 Glass balls 4 mm 59.91 Salbutamol 0.15 15 Ethanol 39.50 Distilled water 0.40 Glyceri.n 0.04 Composition 11 Glass balls 4 mm 59.66 20 Ethanol 39.73 Distilled water 0.40 Glycerin 0.06 Salbutamol 0.15 Composition 12 Glass balls 4 mm 57.31 Salbutamol 0.15 Xylitol 1.73 Distilled water 2.60 Ethanol 37.78 :
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7 ~7 Distilled water 0.38 &lycerin 0.05 Composition 13 Glass balls 4 mm 73.03 Salbutamol 0.18
It wil]. be seen from the above discussion of dimensions that the device of the present invention can indeed be made extremely smallj in contrast to presently available inhalers.
Figure 8 shows part of a prototype of the inhaler according to the inventionj composed of three aluminium elements. ~he three elements are a lower support body la with a circular orbltal path 3a, an upper cover-plate 2a with a circular air passage 8a forming the air outlet and an exchangeable insert body , 7~L
llj the top lla of which constitutes the central area of the orbital path 3a. ~his prototype has been used to test various geometrical configurations of the central area of the orbital path.
As can be seen in Figure ~, the frusto-conical path llb of top lla of the insert body 11 has a spiral formj by virtue of which the cross-section of the annular clearance 7a forming the centripetal air discharge system widens from a minimum immediately after the junction with the air intake conduit up to a maximum immediately before the air intake conduit.
With reference to Figures 9 and 10, which show the insert body in elevation and top viewj a brief description will now be given of t,he production of the spira:L form mentioned above by means of an end-milling cutter. l'he insert body 11 s-tarts with the shape illustrated in the upper portion of Figure 9, that is to sayj the top has a lower cylindrical portion surmounted by a frusto-conical portion having a cone angle of 90. ~he insert body 11 is then slowly turned about its vertical axis and at the same time a milling cutter is slowly advanced towards -the a~is of rotation of the insert body. ~he milling cutter is a tool approximately 4 to 5 mm in diameterj and the axis of rotation of the milling cutter is denoted ~27~37~
by reference numeral 12 in Figure 9. ~he insert body 11 is rotated through an angle of 330 while the milling cutter advances, and this produces the spiral form shown in Figures 8 to 10.
As a result of the spiral form of the central area of the orbital pathj the cross-section of the air discharge annular clearance is relatively small in the first propulsion phase of the ball, a phase which can be regarded as extending for about 120 from immediately after the opening of the air intal~e conduit into the orbital path. During this phase little air can flow out of the orbital path. ~here-after a second phase ensues during which the cross-section of the clearance becomes progressively wider so that more and more air can be discharged from the annular path. It will be appreciated that there is no definite division between the two phases, since the increase in t~e width of the annular clearance is continuous. During the first phase effective propulsion of the ball is achievedj the aim being to get as high a rotational speed for the ball as possible. During the second phase the ball continues to be propelled ; but larger amounts of air are lost from the region ahead of the ball, the alr taking with it particulate material to be inhaled. ~he second phase ensures that - . ....
. .. .~" .;.
the desired amount of parti.culate material can be inhaled at an acceptably low suction pressure.
It has been found that an orbital path deviating slightly from a circular form may be useful, since periodic acceleration effects on the ball tend to result in improved removal of active substance from the surface of the ball and/or the surface o~ the orbital path, and in improved aerosol formation. Such periodic acceleration forces may be brought about by using an elliptical pathj or by using a generally circular path with a plurality of convex or concave indenta-tionsj for example from two to four such indentations. In either case, deviations from the circular form should not be too great or else the braking ef:eect on the ball will become too large.
With elliptical paths an ellipticity coefficient of about 1.25 has proved to be suitable.
Fi~ures 11 and 12 are diagrams illustrating two examples of circular paths with convex and concave indentations respectively. Arrow 13 indicates the direction of air intake into the orbital path. ~he deviation from the circular form marked with d may amount to about 1/25 of the diame-ter of the circular path.
l'he device according to the present invention , may be used for inhala-tion either through the mouth or through the nose. In order to make the device easier to use an outlet member in the form of a mouthpiece or nose-piece, as the case may requirej may be mounted on the cover sheet 2 to communicate with the air outlet opening 8. Fig-ure 13 is a perspective view of a device according to the invention having a mouthpiece; which is denoted by reference numeral 20. In other respects the device of Figure 13 is broadly the same as that of ~igures 5 to 7j and the same reference numerals are therefore used in Figure 13 as in those Figures.
~ he provision of such an outlet member becomes parti-cularly valuable in connection with the further embodiment of the inven-tion which is shown in Figure 14~ In the em-bodiment of Figure 14 the intake conduit 5 is omitted andair enters the orbital path 3 through an air inlet 6' pro-vided in the supportl' rather than the cover-sheet 2'. rhe cover-~heet 2' contains only the air outlet 8. Both the support 1' and the cover-sheet 2' are reduced in siæe com-pared to the previously described embodirnentsj and are shown in Figure 14 as being circular in form. rhis em-bodiment is so small that it is very desirable to include an outlet member in the form of a mouthpiece or nosepiece to enable the device to be conveniently handled by a user.
~he body of the inhaler according to the present in-ventionj i.e. the support 1 or 1' and cover-sheet 2 or 2' may suitably be made of a plas-tics materialj for example ABSj the support being either an injection-moulded part formed from a plastics granulatej or a : , :
.
: .-.,.' "''; ' ~
1~707~
deep-drawn moulding formed of plastics sheeting which is heated and formed over a mould. Injection-moulding is presently preferred since that process allows for higher precision. Alternatively, the body of the inhaler may be formed from a metal, such as aluminium, the desired form being achieved by stamping or by deep-drawing.
~ he support and cover-sheet may be joined by a variety of methods, depending on the materials involved, including ultrasonic weldingj anodic bonding, or adhesion. If adhesion is used the amount of adhesive the pattern in which adhesive is applied and the contact pressure used must be such that penetration of the adhesive into the path of the ball is avoided.
~he ball may be made of glassj metal, a plastics materialj a ceramic material, for e~ample alumina.
For reasons already mentionedj it is preferred that the surface of the ball and/or the surface of the orbital pathj should be non-smooth. In the case of glass ballsj a rough ground surface gives the desired effectj and permits good adhesion of the active substance when applied thereto byj wetting with a solution of the active substance and subsequent evaporation of the solvent. ~he manner of applying the active substance to the glass balls is described in more detail below. Alternativelyj the ball may have .
~'~7~
a surface structure similar to that of a golf ball.
If the surface of the orbital path is non-smoothj and possiblyj the active substance applied also to the orbital pathj the glass ball used may be acid-treated.
In addition to any surface characteristicswhich the surface of the orbital path may have to render it non-smoothj the orbital path surface preferably has helical grooves formed therein e~tending along the direction of movement of the ballj similar to the ri~lings in firearms. Contact of the ball with the grooved helical path causes the ball to spin perpendicular to the direction of travel. ~his is believed to be of particular advantage in relation to the dispersion of the active substance in -the air.
~he helical grooves may be formed in the orbital path during the injection-mouldingjdeep-drawingj stamping or other process by which the support is formed.
~he grinding and dispersing ~unctions of the ball will become clearer on considering the dynamic behaviour of the travelling ball with reference to ~igure ~.
1. Under the influence of centrifugal force~the ball is in rolling contact with the outer annular wall :
,. :~
~7~37~L~
of orbital path 3 (see point of contact B). ~his causes turning of the ball about a~is A.
2. Helical grooving of the surface of the orbital path causes simultaneous turning of the ballj e~g.
in the direction of the arrow, about axis C, which extends perpendicularly to the plane of the drawing.
3. ~he speed gradient between the surface for the ball and the surface of the orbital path continues to increase in the direction of arrows Lj which represent the airflow towards the centripetal discharge system whichj due to the acceleration forces on the particles, contributes to good particle~
air distribution.
rhe i.nhaler according to the invention is suitable for the administration of any pharmacologically active substance that can be inhaled and is absorbed via the mucous membranes of the respiratory passages.
In particular, the inhaler is designed for the treatment of asthma and bronchitis by means of the substances salbutamolj beclomethasone dipropionate, terbutaline and sodium cromoglycate.
. . - ~
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; .;, .
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~ here are several ways of introducing the active substance into the inhalerj and some of these will now be mentioned.
1. ~he active substance is dissolved in a solvent and the ball dipped into it. Upon evaporation of the solvent there remains a film o~ solid active substance.
2. A solution of active substance is introduced into the recess in the support which forms the orbital path. Upon drying a film of active substance remains in the recess.
3. After the complete device has been assembledj including the ballj the active substance is introduced in solution into the orbital pathj and upon evaporation a film of active sub~tance re~ains on the sur~ace O:e the orbital path and may remain also on the sur~ace o~ the ball.
4. ~he substance is introduced in solid ~orm into the device after assembly. In this case the particulate material simply lies on the surface o~ the orbital path without being attached thereto as it is when it is present as a film.
If the active substance is applied in solution and if the inhaler body is made of a plastics materialj account may need to be taken of the possibility that the - . ~
.. ..
.. . :: ..
.:' ' :
~L27~U
solvent used may interact with the plastics materialj for example by dissolving out the plasticizer. If such an effect is anticipated the body of the inhaler can be subjected to a process of metal coating by vaporization to prevent it being attacked by the solvent.
Due to the rotation of the ballj the solid particles are finely ground or dispersed and have a diameter on leaving the inhaler such that a fraction of the particles in the range of 10 to 20 microns can be inhaled. ~he total quantity of active substance which needs to leave the inhaler will depend on the nature of the active substance itself and the dosage requirements.
For examplej for salbutamolj a typical dose is from 200 to 400 ~g.
As already mentioned, a single inhaler may be provided with more than one ball. For examplej where the orbital path has a width of 3.7 mm a pair of balls 3.5 and 3 mm in diameter may be usedj and where the orbital path has a width of ~.3 mm a pair of balls 4.1 mm and 3.7 mm may be used. ~hese dimensions are given by way of e~ample only~ and other dimensions could be used. In each case the larger ball is the one to which the air provides the main propulsive ~orce. ~he smaller ball being propelled mainly by impact with the larger ball. Where two .7 , .
balls are used both can carry the same active substance but an alternative possibility is that each may carry a different active substance. ~or example, it is sometimes necessary for salbutamol and beclomethasone dipropionate to be administered together, in which case one of the balls may be coated with one of these substance and the other ball may be coated with the other.
One further possibility afforded by the use of a plurality of balls is that one of the balls may consist purely of the active substance, or a mi~ture of active substance and an inert carrierj rather than having the active substance merely as a coating on an inert substrate such as glass. In this case the other ball or balls may carry active substance or may consist purely of the inert substrate in this case the ball of pure drug would no-t be the largest o~ the balls so that the main propulsive force would be applied to the other ballj or one o~ the other balls, as the case may be.
Some examples will now be given of compositions used to coat salbutamol onto glass balls by the solvent method referred to above. ~he compositions are given in terms of percentage by weight.
Composition 1 Glass balls 4 mm 59.95 Salbutamol 0.08 Ethanol 39.97 ,: :
' ' '~
7~)7~
Composition 2 Glass balls 4 mm57 49 Salbutamol 0.08 Ethanol 42.43 Composition 3 Glass balls 4 mm- 59.37 Salbutamol 0.08 Polyvinylpyrrolidone 0.008 Ethanol 40.542 Compositon 4 Glass balls 4 mm98.96 Salbutamol 0.17 Ethanol 0.87 Composition 5 Glass balls 3 mm95.34 Salbutamol 0.58 Polyvinylpyrrolidone 0.58 Ethanol 3.50 Composition 6 Glass balls 4 mm82.22 Salbutamol 1.49 Polyvinylpyrrolidcne 1.49 Ethanol 14.80 Composition 7 Glass balls 4 mm53.91 Salbutamol 0.09 Ethanol 46.00 Composition 8 Glass balls 4 mm 95.71 Salbutamol 0.12 Polyvinylpyrrolidone 0.07 Ethanol 4.10 Composition 9 Glass balls 3 mm 91.95 Salbutamol 0.56 Polyvinylpyrrolidone 0.09 10 Ethanol 7.40 Composition 10 Glass balls 4 mm 59.91 Salbutamol 0.15 15 Ethanol 39.50 Distilled water 0.40 Glyceri.n 0.04 Composition 11 Glass balls 4 mm 59.66 20 Ethanol 39.73 Distilled water 0.40 Glycerin 0.06 Salbutamol 0.15 Composition 12 Glass balls 4 mm 57.31 Salbutamol 0.15 Xylitol 1.73 Distilled water 2.60 Ethanol 37.78 :
- .
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, .
7 ~7 Distilled water 0.38 &lycerin 0.05 Composition 13 Glass balls 4 mm 73.03 Salbutamol 0.18
5. Xylitol 1.70 Distilled water ` 2.64 Ethanol 22.00 Dis-tilled water 0.22 Glycerin 0.23 10 Notes 1. In the case of compositions 10 to 13, glycerin serves as an adhesive to improve retention of salbutamol on the balls.
2. Xylitolj included in compositions 12 ~nd 13, also serves as an adhesive.
3. ~he distilled water referred to in compositions 10 and llj and the second mentioned quantity of distilled water referred to in composi-tions 12 and 13, serves as a plasticisar for tlle salbuta~ol. ~he first mentioned quan-tity of distilled water in compositions 12 and 13 serves as a solvent for the ~ylitol.
4. In the case of compositions 1 to 11, salbutamol alone, or with an adhesivej was dissolved in ethanol, and this solution was sprayed onto the glass balls rotating in a coating pan by means of a hand-held spray gun. ~he coated balls were dried at 40C by means of a hot-air blower. In the case of compositions `^` ~7~L
12 and 13j the solution of xylitol in distilled water was sprayed onto the balls before the solution of salbutamol and adhesive was similarly applied.
~ he solvent used for applying a film of active substance to the balls or orbital path will of course depend on the nature of t~e active substance.
For examplej where the active substance is beclomethasone dipropionate the solvent may be chloroform, methylene chloride; dichloroethane acetone, methanolj ethanol, ethyl acetate or methyl isobutyl ketone.
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2. Xylitolj included in compositions 12 ~nd 13, also serves as an adhesive.
3. ~he distilled water referred to in compositions 10 and llj and the second mentioned quantity of distilled water referred to in composi-tions 12 and 13, serves as a plasticisar for tlle salbuta~ol. ~he first mentioned quan-tity of distilled water in compositions 12 and 13 serves as a solvent for the ~ylitol.
4. In the case of compositions 1 to 11, salbutamol alone, or with an adhesivej was dissolved in ethanol, and this solution was sprayed onto the glass balls rotating in a coating pan by means of a hand-held spray gun. ~he coated balls were dried at 40C by means of a hot-air blower. In the case of compositions `^` ~7~L
12 and 13j the solution of xylitol in distilled water was sprayed onto the balls before the solution of salbutamol and adhesive was similarly applied.
~ he solvent used for applying a film of active substance to the balls or orbital path will of course depend on the nature of t~e active substance.
For examplej where the active substance is beclomethasone dipropionate the solvent may be chloroform, methylene chloride; dichloroethane acetone, methanolj ethanol, ethyl acetate or methyl isobutyl ketone.
, .~..
: . . : : ,., , , . :- -: : , , ::
Claims (16)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. An inhaler for introducing a solid substance in particulate form into the inhaled air of a user, comprising (a) a body having (1) an internal surface defining an endless path, (2) an intake conduit for the inhaled air, the air intake conduit opening tangentially into said endless path, and (3) an air outlet adapted for fluid communication with a breathing passage of the user and discharge means for the inhaled air in fluid communication with said endless path and the air outlet, and said air outlet and discharge means being disposed centripetally relative to the endless path whereby inhalation by the user through the outlet causes air to flow through the air intake conduit, the endless path and the discharge means to the outlet, (b) a ball having a surface and being disposed in said endless path, the ball being arranged in said endless path -to circulate therearound under the effect of the air flow, and (c) a solid medicament substance distributed between the surface of the endless path and the ball.
2. The inhaler according to claim 1, wherein the solid substance is distributed over the surface of the endless path.
3. The inhaler according to claim 1, wherein the solid substance is distributed over the surface of the ball.
4. The inhaler according to claim 1, wherein the solid substance is distributed over the surfaces of the endless path and the ball.
5. The inhaler according to claim 1, wherein said body comprises a support and a cover sheet on said support, the support defining a first recess which constitutes said internal surface and a second recess defining the intake conduit for the inhaled air, and the cover sheet overlying the recesses and defining an air inlet fluidically communicating with the second recess and the air outlet.
6. An inhaler according to claim 5, wherein said air inlet and said air outlet have the form of circular openings in the cover sheet.
7. An inhaler according to claim 6 r wherein a film is removably secured to the cover sheet to close said circular openings.
8. An inhaler according to claim 7, wherein the film is a metal foil.
9. An inhaler according to claim 7, wherein the film is a laminated film composed of a paper film and an aluminium film, the latter film being located on the side facing said circular openings.
10. The inhaler according to claim 5, wherein the portion of the support disposed centripetally relative to the endless path is sized and shaped to define an annular clearance between the support and the cover sheet, and said annular clearance comprises said air discharge means.
11. The inhaler according to claim 10, wherein the annular clearance has a cross-section increasing in the direction of circulation of the ball from a minimum at a point immediately after the air intake conduit opens into said endless path to a maximum immediately prior to said point.
12. The inhaler of claim 11, wherein said portion of said support disposed centripetally relative to the endless path has a spiral surface defining the increasing cross-section of the annular clearance.
13. An inhaler according to claim 1, wherein said path is circular in shape.
14. An inhaler according to claim 13, wherein said circular path in diametrical view, has from 2 to 4 indentations, with a maximum deviation from the circular path of approximately 1/25 of the diameter of the circular path.
15. The inhaler according to claim 1, wherein at least one of the surfaces is rough.
16. The inhaler according to claim 1, wherein said body comprises a support and a cover sheet on said support, the support defining a first recess which constitutes said internal surface and a second recess extending to the periphery of the support and defining the intake conduit for the inhaled air, and the cover sheet overlying the recesses and defining the air outlet.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT2272/85 | 1985-08-01 | ||
| AT0227285A AT384552B (en) | 1985-08-01 | 1985-08-01 | INHALATION DEVICE FOR DOSING AND DISTRIBUTING SOLID BODIES INTO THE BREATHING AIR |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1270711A true CA1270711A (en) | 1990-06-26 |
Family
ID=3531262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000515100A Expired CA1270711A (en) | 1985-08-01 | 1986-07-31 | Inhaler |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4841964A (en) |
| EP (1) | EP0215559B1 (en) |
| JP (1) | JPS6234573A (en) |
| AT (2) | AT384552B (en) |
| AU (1) | AU6075986A (en) |
| CA (1) | CA1270711A (en) |
| DE (1) | DE3668783D1 (en) |
| DK (1) | DK162740C (en) |
| FI (1) | FI89331C (en) |
| GB (1) | GB2179260A (en) |
| GR (1) | GR861996B (en) |
| IE (1) | IE59027B1 (en) |
| NZ (1) | NZ217045A (en) |
| PT (1) | PT83126B (en) |
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|---|---|---|---|---|
| BE483136A (en) * | 1947-09-04 | 1942-06-30 | ||
| US2534636A (en) * | 1949-02-12 | 1950-12-19 | American Cyanamid Co | Powder dispenser |
| US2816549A (en) * | 1956-11-16 | 1957-12-17 | Isaac E Webster | Dispensing device |
| US3809084A (en) * | 1970-02-16 | 1974-05-07 | American Cyanamid Co | Pressurized portable dispenser |
| US4069819A (en) * | 1973-04-13 | 1978-01-24 | Societa Farmaceutici S.P.A. | Inhalation device |
| EP0041783B1 (en) * | 1980-06-06 | 1984-12-05 | FISONS plc | Inhalation device for powdered medicaments |
-
1985
- 1985-08-01 AT AT0227285A patent/AT384552B/en not_active IP Right Cessation
-
1986
- 1986-07-29 GR GR861996A patent/GR861996B/en unknown
- 1986-07-31 DE DE8686305887T patent/DE3668783D1/en not_active Expired - Fee Related
- 1986-07-31 US US06/892,197 patent/US4841964A/en not_active Expired - Fee Related
- 1986-07-31 IE IE206086A patent/IE59027B1/en not_active IP Right Cessation
- 1986-07-31 EP EP86305887A patent/EP0215559B1/en not_active Expired
- 1986-07-31 CA CA000515100A patent/CA1270711A/en not_active Expired
- 1986-07-31 DK DK365986A patent/DK162740C/en not_active IP Right Cessation
- 1986-07-31 GB GB08618762A patent/GB2179260A/en not_active Withdrawn
- 1986-07-31 AT AT86305887T patent/ATE50147T1/en not_active IP Right Cessation
- 1986-07-31 NZ NZ217045A patent/NZ217045A/en unknown
- 1986-07-31 FI FI863127A patent/FI89331C/en not_active IP Right Cessation
- 1986-07-31 AU AU60759/86A patent/AU6075986A/en not_active Abandoned
- 1986-08-01 PT PT83126A patent/PT83126B/en not_active IP Right Cessation
- 1986-08-01 JP JP61180270A patent/JPS6234573A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| GB2179260A (en) | 1987-03-04 |
| DE3668783D1 (en) | 1990-03-15 |
| PT83126A (en) | 1987-02-27 |
| PT83126B (en) | 1993-05-31 |
| DK365986A (en) | 1987-02-02 |
| AT384552B (en) | 1987-12-10 |
| AU6075986A (en) | 1987-02-05 |
| JPS6234573A (en) | 1987-02-14 |
| ATA227285A (en) | 1987-05-15 |
| NZ217045A (en) | 1989-04-26 |
| IE862060L (en) | 1987-02-01 |
| EP0215559B1 (en) | 1990-02-07 |
| IE59027B1 (en) | 1993-12-15 |
| FI863127A0 (en) | 1986-07-31 |
| DK365986D0 (en) | 1986-07-31 |
| JPH0234620B2 (en) | 1990-08-06 |
| DK162740C (en) | 1992-04-27 |
| FI89331C (en) | 1993-09-27 |
| GB8618762D0 (en) | 1986-09-10 |
| FI863127A (en) | 1987-02-02 |
| GR861996B (en) | 1986-11-24 |
| EP0215559A1 (en) | 1987-03-25 |
| DK162740B (en) | 1991-12-09 |
| US4841964A (en) | 1989-06-27 |
| ATE50147T1 (en) | 1990-02-15 |
| FI89331B (en) | 1993-06-15 |
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Legal Events
| Date | Code | Title | Description |
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| MKLA | Lapsed |