US 3669113 A
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nited States Patent Altounyan et a1. June 13, 1972  INHALATION DEVICE  Inventors: Roger Edward Collingwood Altounyan,  References Cited Wilm l Eng n H ry Ho ll, UNITED STATES PATENTS deceased, late of Castle Donnington, En-
gland Eunice Cockbum Howe, executrix 2,573,918 1 1/195] MCCUlSlOll 128/206 Assignee: Fisons, Limited, London, England Filed: June 18, 1969 Appl. No.: 871,468
Related US. Application Data Continuation-in-part of Ser. No. 745,774, July 18, 1968, which is a continuation-in-part of Ser. No. 532,271, March 7, 1966.
Foreign Application Priority Data [1.8. CI ..l28/266 ..A6lm 15/00 Field of Search 128/266, 206, 208
Primary Examiner-Robert W. Michell Attorney-Wenderoth, Lind & Ponack  ABSTRACT A method and device for dispensing a particulate medicament material from a container. The container provided with at least one powder outlet is rotated by pneumatic means about an axis of the container. The axis of rotation is caused to precess so as to describe a path of precession which is contained within a generally conical surface of precession, and the axis of rotation of the container is at an angle to the axis of the generally conical surfaces of precession. This causes the walls of the container to undergo repeated changes in radial acceleration with respect to the axis of the generally conical surface of precession, which changes of acceleration are of sufficient magnitude to overcome the centrifugal and cohesive forces which hold the particles of powder in place upon the wall of the container.
25 Claims, 10 Drawing Figures PATENTEmun I3 1312 3.669.113
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INVENTORS ROGER E.C. ALTOUNYAN HARRY HOWELL ATTORNEYS PATENTEDJuu 13 I972 SHEET 2 UF 5 INVENTORS ROGER E.C. ALTOUNYAN HARRY HOWELL BY M fl 7M ATTORNEYS PATENTEDJlm 13 I972 3.669.113
SHEET 3UP 5 I v /-4 I I 3 q \Sa IO FIG 4 INVENTOR ROGER E.C.ALTOUNYAN HARRY HOWELL BY e ATTORNEY PATENTEDJUN 13 I972 sum u or 5 FIG.6
FIGJO INVENTORS ROGER E.C.ALTOUNYAN HARRY HOWELL ATTORNEYS INHALATION DEVICE This application is a continuation-in-part of our application Ser. No. 745,774, filed July 18, 1968, which in turn was a continuation-in-part of our application Ser. No. 532,271, filed Mar. 7, 1966.
The present invention relates to a method whereby particulate medicament materials may be dispersed from a container using a fluidization technique. The invention also provides devices for use in the method of the invention.
Accordingly, the present invention provides a method for dispensing a particulate medicament material from a container which comprises rotating a container provided with at least one powder outlet by pneumatic means about an axis thereof and causing the axis of rotation to precess so as to describe a path of precession which is contained within a generally conical surface of precession. By generally conical is meant a surface of precession which is a cone or frusto-cone of precession. The axis of rotation of the container being at an angle to the axis of the cone or frusto-cone of precession. By the expression at an angle to is meant an axis of rotation which intersects the axis of the cone or frusto-cone of precession as well as an axis of rotation which does not intersect said axis of the cone or frusto-cone of precession. The walls of the container undergo repeated changes in radial acceleration with respect to the axis of the cone or frusto-cone of precession, which changes of acceleration are of sufficient magnitude to overcome the centrifugal and cohesive forces which hold the particles in place upon the wall of the container.
We believe that during the motion generated by the method of the invention any point on the wall of the container executes a motion of a trochoidal nature in the radial plane of the cone or frusto-cone of precession. The trochoidal motion may be epitrochoidal or hypotrochoidal. As the container rotates, particulate material is centrifuged against the container wall and is held in place thereby frictional and cohesive forces. During the trochoidal motion the particles are subjected to several changes in radial acceleration of the wall of the container. If the acceleration of the wall of the container away from the axis of the cone or frusto-cone of precession is sufficiently great, the forces holding the particles in place upon the wall are overcome. The particles then leave the wall and adopt free flight within the container whose walls continue to move along the trochoidal curve. The particles later impinge upon the container wall at a different point to that at which their free flight was initiated. It is believed that, since the containers axis of rotation is inclined to the axis of the cone or frusto-cone of precession, the particles impinge upon the container wall at a point displaced along the axis of the container. The particles thus undergo fluidization within the container and also axial feed along the container.
The occurrence of fluidization and the rate and extent of movement of particles within the container are dependent upon a number of inter'related factors, such as the relative diameters of the container and the cone or frusto-cone of precession at the base of the container, the speed of rotation of the container, the relative angular speeds of rotation of the container and its precession, the size of the included angle of the cone or frusto-cone of precession, the nature of the-particulate material within the container and its interaction with the material of the container wall.
The motion generated by the method of the invention consists in essence of a circular sequence of cusps leading into one another at nodes, which may be transition curves, simple points or small loops linking one cusp to the next. The magnitude of the variations in radial acceleration undergone by a point on the container wall depends upon the number of cusps which occur during each revolution of the container about the axis of precession and upon the difference between the apogee and perigee of the locus of the point on the container wall as it moves around the axis of precession. These variables are themselves functions of the factors referred to above and may be varied over a wide range according to the form and size of the device used to generate the required motion. However, the energy available to fluidize powder on the container wall during the traversal of each cusp is inversely proportional to the number of nodes occurring per rotation of the container axis about the axis of precession, or the nodal number as this ratio will be termed hereinafter. At excessively high or low nodal numbers fluidization within the container may be inadequate and we prefer that the nodal number should be from 2 to 25, preferably 3 to 10, to achieve satisfactory fluidization. The nodal number need not be an integer. As will be shown later. the nodal number is a function of the dimensions of the device generating the motion. Having established suitable dimensions for a device so as to achieve the desired nodal number, the difference between the apogee and perigee of the locus of a given point on the wall of the container may be varied to secure fluidization. This variation may be achieved by altering the size of the included angle of the cone or frusto-cone of precession and/or by altering the radius of the container and/or by altering the distance of the container from the apex or notional apex of the cone or frusto-cone of precession, which effectively alters the diameter of the cone or frusto-cone of precession at the container. A decrease in the container radius or an increase in the distance between the container and the apex of the cone or frusto-cone promotes fluidization. It will of course be appreciated that these factors are inter-related with the nodal number and that fluidization may be achieved by many permutations of these factors. However, if the included angle of the cone or frusto-cone of precession is high, say 60 or more, then the rate of axial feed of particles within the container is extremely rapid. Whilst movement of particles along the axis of the container will occur at very small cone angles, e.g. less than about 0.5, such movement will be relatively slow. An included angle of about 1 to preferably about 2, will usually give an adequate rate of movement, provided that adequate fluidization occurs.
The other factors referred to above are not readily susceptible to such generalized statements in view of their close interrelationship and their dependence upon the size and nature of the device generating the motion and its intended use.
The motion required by the method of the invention may be generated by a number of fonns of device. For example, the container may be mounted upon a rigid shaft having a universal joint therein. The free end of the shaft is rotatably mounted by means of a conventional lubricated bearing assembly, such as a ball or roller race or a bush type bearing. Between the container and the universal joint is a bearing adapted to retain the angle of the cone of precession of the shaft within the desired range. This may take the form of an annular ring surrounding the shaft and which engages with a bearing shoulder on the shaft (this type of device generates hypotrochoidal motion), or may take the form of an annular shoulder on the shaft which shoulder is provided with a dependent annular bearing skirt whose inside surface engages with the outside bearing surface of a fixed annular ring of smaller diameter (this type of device generates epitochoidal motion). In an alternative form, the universal joint may be replaced by a flexible shaft. Furthermore, by introducing assymetric flexibility into the shaft, for example by making it with a polygonal cross-section e.g. a triangular, square or hexagonal section, it may not be necessary to provide the restraining bearing.
The motion may also be generated by a rigid shaft carrying the powder container rotating within two spaced annular bearing rings of different diameters. The annular bearing rings may take the form of a tapered bearing tube where contact between the shaft and bearing occurs at the top and bottom extremes of the tube, and the term bearing ring is used herein to denote not only an annular bearing surfaced member, but also an annular area of contact between a shaft and a bearing surface. Such a bearing tube may be provided with a ridge or an inserted protruding lip at its top and/or bottom extremes to provide the contacting bearing rings or may be concaved between its ends to achieve the same effect. Alternatively the bearing rings may be of the same diameter and the shaft be tapered. It will also be appreciated that the shaft may be the stationary member and that the powder container may be carried by the tapered bearing tube. The difference in diameter between the shaft and the bearing rings afiect the nature of the motion generated.
During the motion generated by the above devices, each contact between the shaft and a bearing ring will generate a motion wherein the ratio of the frequency of rotation of the container about the axis of the cone or frusto-cone of precession to the frequency of rotation of the container about its own axis (or the frequency ratio as this ratio will be termed herein) is dependent on the ratio of the diameter of the moving member to the difference in diameters of the moving and stationary members. The greater the difference in diameters between the moving and stationary members, the more eccentric and in general more dominant will be the trochoidal motion generated by that contact. Where the moving member rotates within the stationary member, the nodal number is one more than the frequency ration, whereas where the moving member rotates around the outside of the stationary member, the nodal number is one less than the frequency ratio. Each bearing ring, or its equivalent, generates its own trochoidal motion and, where there are two bearing rings, these motions combine to yield an overall resultant motion for the free end of the shaft.
It is desirable that the effect of the non-dominant motion should either be minimized or should complement the motion generated by the dominant bearing ring. Whilst the latter may be achieved by ensuring that the nodal number of the nondominant motion is an integer multiple of, e.g. 2, 3 or 4 times, the nodal number of the dominant motion, such an exact relationship may prove difficult to achieve in practice. We therefore prefer to minimize the effect of the non-dominant motion. Usually the non-dominant motion is generated by the smaller bearing ring and the effect of the motion of this ring may be minimized by decreasing the total clearance between the shaft and this bearing ring. This increases the nodal number of the motion generated and we have found that in general, if the nodal number at a point on the container wall of the non-dominant motion is in excess of 15, preferably in excess of 30, the effect of this motion is reduced to a satisfactory extent.
it will be appreciated that the distance between the bearing rings and the clearances between the shaft and the bearing rings will determine the included angle of the cone or frustocone of precession.
A particularly preferred form of bearing ring and shaft for generating the motion required by the method of the invention is one wherein a rigid substantially uniform cylindrical shaft is journalled in an internally tapered bearing tube, notably one wherein the bearing tube has an internal diameter at its inner end (i.e. that end housing the free end of the shaft) which is smaller than the internal diameter at its outer end. It is especially. preferred that the shaft be the stationary member and that the bearing tube be rotatably mounted on the shaft. With such a device, fluidization within a container mounted on the bearing tube will occur when the changes in radial acceleration undergone by the container wall due to the motion generated by the dominant contact between the shaft and bearing are sufficiently large to overcome not only any conflicting acceleration generated by the non-dominant contact and the cohesive forces amongst the particles and between the particles and the container wall, but also overcome the centrifugal forces generated during the motion. In an ideal case the effects of the non-dominant motion would be nil and, if one ignores inter-particle forces, we have found that fluidization in such an ideal case will occur at a given point on the container wall when the tapered bearing tube is rotated in rolling contact upon the stationary shaft if the expression:
a/h (R/R-r) R is satisfied, a is the distance of the base of the parallel walled section of the container from the non-dominant contact between the shaft and bearing, 11 is the distance between the dominant and non-dominant contacts between shaft and bearing, R is the internal radius of the bearing at the dominant contact, r is the radius of the shaft and R is the internal radius of the container at a distance a from the non-dominant contact between the shaft and bearing. Usually the limiting case for fluidization will be at the base of the powder container where this has a flat bottom and parallel side walls. However, where the container has a rounded bottom, the limiting case may be at some point above the base, for example at the start of the parallel walled portion thereof. The limiting case may be readily ascertained.
It must be emphasized that the above expression represents the minimum requirements for fluidization under the conditions specified. However, inter-particle forces must also be overcome and the non-dominant motion may conflict with the dominant motion to reduce the fluidizing forces generated. The left hand side of the above expression must therefore in practice exceed the right hand side by an amount which will vary according to the above factors. In practice, therefore, the approximate dimensions for a device established from the above expression may require optimisation by experimentation. It will be appreciated that a satisfactory device for present use may be constructed using a wide range of dimensions in a number of permutations. However, various of the dimensions of this preferred form of device for present use may be limited by certain factors, thus reducing the number of possible permutations which may be made. For example, the energy available in the driving gas stream will impose limitations on the possible size of the device as may the strength of the materials used to construct the device; and, where the device is to be carried in the pocket of a user, it clearly cannot exceed, say, 6 inches in total length. Furthermore, the powder container to be used in the device may be of a standard specified form and size since medicaments are usually put up in standard gelatin capsules holding, say, 20 mgs of drug. For efficient operation the capsule is filled with powder only to one-half to one-third of its total capacity.
In the form of device where a shaft is journalled in a tapered bearing tube, it is preferred that the non-dominant contact between the shaft and bearing generate a motion at the container wall having a nodal number in excess of 15, preferably in excess of 30, and that the dominant contact generate a motion at the container wall having a nodal number of from 2 to 25, e.g. 3 to 10 notably 5 to 7. A suitable motion may, for example, be generated by rolling contact between a cylindrical shaft and a tapered bearing tube which has an internal diameter at one end which is from 1.5 to 6 percent, preferably 2.5 to 9 percent, notably about 3.5 percent, greater than the diameter of the shaft and an internal diameter at its outer end which is equal to the diameter of the shaft plus from 1.3 to 3.5 percent, notably about 2.5 percent, of the internal length of the bearing tube. In general it is desirable to use as fine a rigid shaft as possible, for example a drawn wire shaft of about 0.080 inches diameter may be used in devices powered by human inhalation. Typically, the bearing tube may have an internal length which is 4 to 10, preferably about 7, times the diameter of the shaft.
It is also preferred that the shaft have a rounded free end which bears against the flat closed end of the bearing tube. The free end of the shaft may be of frusto-conical shape, preferably terminating in an hemispherical tip, which tip has a diameter approximately half that of the shaft.
The expression a/h (R /R--r) R quoted above is in relation to a device where a tapered bearing tube is rotatably mounted upon a rigid cylindrical shaft. However, where the bearing tube is stationary and it is the shaft which rotates in rolling contact with the bearing, fluidization of powder within a container mounted on the shaft will occur under the idealized conditions when a/h (FIR-r) R,; a, h, r, R and R having the same values as quoted earlier.
In a further form of device, the use of an integral restraining bearing surface and of a shaft journalled in a bearing tube are combined by providing the container carrier with a short tapered shaft which is mounted centrally within a dependent cylindrical sleeve having an internal dry friction bearing surface. The short shaft is journalled in a tapered recess in the end of a rigidly mounted cylindrical boss or shaft. The dimensions of the recess and of the short shaft are such that the dry friction bearing surface on the dependent skirt can bear against the exterior of the rigidly mounted boss or shaft to provide the drive whereby the freely rotating short shaft is caused to precess.
In the forms of the shaft and bearing configuration described above, the contact between the shaft and that bearing ring generating the dominant motion must be frictional in order that precession may take place. It is preferred that the contact be rolling and, in order to ensure uniform motion of the container walls, that this rolling contact be maintained at substantially all times during the motion. Where two bearing rings are used to generate the motion, the contact between the shaft and the non-dominant bearing ring need not be frictional and in some cases it may be feasible to lubricate this bearing ring, but not the other, in order to minimize any motion generated by this bearing ring.
In the mechanisms described above, precession has been achieved by the fact that the axis of the rotating member upon which the container is mounted sweeps out a conical or as near conical surface as can be achieved in practice; that the rotating member or an integral part thereof bears against a stationary member; and that the contact between the rotating and the stationary members is frictional, preferably a rolling contact.
Accordingly, from a further aspect the invention provides an apparatus for use in the method of the invention which comprises a bearing member having an annular bearing surface and a shaft journalled loosely in the bearing member, one of said bearing and said shaft being stationary, the other being adapted to be rotated by pneumatic means and to receive a container, the rotatable member being capable of being displaced during rotation thereof at an angle about the axis of the stationary member, the annular bearing surface of the bearing member and the shaft or an integral part thereof being adapted to contact one another in a frictional contact during rotation of the rotatable member. In many cases the design of the stationary and rotatable member will be such that the rotatable member inherently adopts at all times a position where its axis is displaced at an angle to the axis of the stationary member, e.g. as is the case where a stationary shaft carries a loose fitting bearing tube which even at rest will tend to adopt a canted position vis a vis the shaft. However, in some cases, the rotatable member may adopt a substantially coaxial position with respect to the stationary member when at rest, as is the case with a flexible shaft surrounded by a restraining bearing ring as described above, yet during rotation may be deflected or whip so that the rotating member and the stationary bearing surface may come into contact to generate the desired precession.
Other mechanisms may readily be devised, such as epicyclic gear systems and the like, which will cause the container to rotate and precess in the manner required. Thus, a further form of mechanism is a shaft freely journalled in a bearing, the requisite wobble in the rotation of the shaft being achieved by means of the repeated attraction and repulsion of magnets mounted in the housing or shaft and the bearing. Alternatively, the precession of the container axis within a cone or frustocone of precession may be achieved by mounting the container at an angle in a cup provided with a vane or vanes, which cup is rotatably mounted off center on a boss provided with a vane or vanes, which boss is itself rotatably mounted. The passage of air past such an arrangement would cause rotation of both the boss and the cup causing the axis of the container to rotate and precess in the desired manner. In these two forms of device the shaft and bearing assemblies should not be in rolling contact, i.e. are in sliding contact, and may be lubricated to assist their relative rotation.
The invention thus also provides an apparatus for use in the method of the invention which comprises a rotatable member carrying means to receive a container, which rotatable member is mounted by means of a shaft journalled within at least one bearing member and is adapted to be rotated pneumatically and to process so that its axis of rotation describes a path contained within a cone or frusto-cone of precession, the axis of rotation of the rotatable member being at an angle to, but not necessarily intersecting, the axis of the cone or frusto cone of precession.
As has been stated above, the rotatable member which is to carry the container is to be rotated pneumatically, for example by a gas stream generated with a rubber squeeze bulb or merely by the inhalation of air by a human user. The pneumatically driven means may take any of the conventional forms, such as a propeller or turbine assembly. Such pneumatically driven means will for convenience be denoted hereinafter by the general term vanes, although this term is intended to include not only a plurality of vanes as with a turbine, but also a single vane as with an Archimedian screw. The vanes may be mounted integrally with the shaft or bearing tube carrying the container, the container receiving means, the container itself, or where the shaft is jointed, as is the case where it has a universal joint, the vanes may be mounted above or below the joint. It is usually preferred to have the vanes mounted integrally with the container receiving means in the form of, say, a propeller and boss on the end of the shaft, or bearing tube, the boss being provided with means for receiving a container.
Usually the gas stream driving the device will flow past the powder container. However, it may be desirable to prevent an excessive flow of driving gas past the container. It is therefore within the scope of the present invention to provide means for isolating the container from the driving gas stream. This may be done for example by providing a shroud, e. g. a sleeve, around the container which effectively channels the gas stream away from the container. Alternatively where the container is mounted on a universally jointed shaft, that portion of the shaft which is supported in the bearing means may be journalled in a chamber separated from that part of the shaft carrying the container and the gas stream only through that chamber.
The powder container for present use may be of any shape or size suited to the intended rate of dispensing and total weight of drug to be dispensed. However, it is preferred that the powder container be a capsule or cartridge, e.g. an hard gelatine capsule, notably one of the gelatine capsules which are of the accepted standard sizes for drug use, e.g. of 20 to mg capacity. Typical of such capsules are those gelatine capsules of internal diameter about 6.3 mms. In order that the medicament powder within the container may be dispensed into the airstream flowing past the container, the container is provided with one or more outlets for the powder. Conveniently, these take the form of perforations in the wall of the container, which holes are preferably symmetrically arranged around the wall. With a gelatin capsule it is preferred that the holes be in a shoulder of the capsule and that they be of from about 0.6 mms to about 0.65 mms in diameter. It will be appreciated that the container should be mounted in any device with the holes in the free end of the container.
The rotating member in devices for present use is provided with means for mounting a powder container thereon. This means is preferably such that the powder container is mounted co-axially with the axis about which the rotating member rotates and is held rigidly in place during operation of the device. This may be achieved by forming a recess in the end of the rotating member which recess is of similar configuration to the powder container and receives the container in a push tight fit. Thus where the rotating member is provided with a terminal boss carrying propeller blades, the boss may be cut with a cup shaped recess to receive a medicament capsule in a push tight fit.
The stationary and rotating members used to generate the motion required by the invention will usually be mounted in an housing adapted to lead the driving gas stream through the vanes by which the rotatable member is to be rotated. This gas stream will also usually flow past the powder container and the housing may therefore take the form of an elongated tube within which the rotating and stationary member are mounted. The stationary member is preferably mounted substantially co-axially with the tubular housing and should be rigidly mounted since undue flexing thereof may cause malfunctioning of the device. The housing may also be provided with other features which may be required for optimum operation of the device. Thus, where the powder container is to dispense powder continuously, means may be provided for supplying powder to the container; means may be provided for generating the driving gas stream, e.g. a rubber squeeze bulb; or the housing may be provided with a non-return valve which permits the passage of gas through the device in only one direction. As indicated below, the method of the invention is of especial use in dispensing powdered medicament into an air stream which is being inhaled. Particularly preferred devices for present use are therefore of a suitable size for convenient use, and are provided with a tubular housing for the stationary and rotating members which housing is provided with a mouthpiece via which the user can inhale air through the device. The rotating and stationary members are preferably mounted within such an housing so that the vanes which are to rotate the rotatable member lie between the intended position of the powder container and the mouthpiece. It is also preferred to provide the housing in devices which are to be driven by the inhalation of air therethrough by a user with a constriction or venturi section in order to increase the air flow rate past the powder container. It will usually be preferred to form the housing in two parts, one having the mouthpiece and the stationary and rotating members and the other having the venturi section and the air inlet. By this means the air inlet may be removed to provide free access to the mounting for the powder container during loading or unloading of the container. If desired, the housing may also be provided with means for piercing the powder container in situ within the device. It may also be desired to provide means, such as a shroud, by which powder issuing from the container may be prevented from depositing upon the contacting surfaces of the stationary and moving members.
The devices for use in the method of the invention may be made from any suitable material such as metal, e.g. steel or aluminum, or a thermoset or thermoplastic synthetic resin, such as polystyrene, nylon, polyethylene, unreaformaldehyde resins and the like. The material used will depend upon the sacle on which the dispensing of powder is to be carried out and the magnitude of the forces generated. The bearing surfaces may also be made from conventional materials. However, where precession is achieved by means of a frictional contact, for example between a shaft and the bush within which it is mounted, such contacting surfaces should not be self lubricating and preferably are made from high friction materials.
The method of the invention finds widespread use wherever it is desired to dispense medicament powders into an airstream. Thus, it may be used to dispense antibiotic and like powders in a cloud for deposition on a wound or skin infection. However, as indicated above, the method finds especial use in the dispensing of medicament into an airstream which is to be inhaled. The method affords a means by which very fine particles may be administered deep into the lungs of a user and, where the device used is one powered by the users inhalation, delivers the powder in an amount proportional to the rate of inhalation and the total volume of air inhaled, thus automatically regulating the release of medicament according to the depth of inhalation.
The method may be used to dispense a wide variety of powdered medicaments and the particles thereof may be of any shape and may be amorphous or crystalline in nature. However, the method of the invention is of especial application in dispensing micronized powders notably those of particle size less than 80 microns many of which have poor flow characteristics and may not be readily dispensed by other methods.
The method of the invention will be described by way of example in relation to various forms of device which may be used to administer powdered medicament by oral inhalation and with reference to the accompanying drawings in which:
FIG. I is a longitudinal section through a simple form of device;
FIG. 2 is a longitudinal section through a preferred form of device;
FIG. 3 is a longitudinal section through a cap suitable for use with the device of FIG. 2;
FIG. 4 is a longitudinal section through an alternative form of the device of FIG. 2 wherein the shaft and bearing tube have been transposed;
FIG. 5 represents an alternative form of bearing tube for use in the devices of FIGS. 2 and 4;
FIG. 6 is a longitudinal section through an alternative form of a simple device for generating the motion required by the method of the invention;
FIG. 7 is a longitudinal section through an alternative form ofthe device of FIG. 6;
FIG. 8 is a diagrammatic longitudinal section through a further alternative form of the device of FIG. 6; and
FIGS. 9 and 10 are diagrammatic longitudinal sections through two further forms of bearing and shaft assembly which may be used to generate the motion of the invention.
Referring now to FIG. 1, an inhalation device comprises a tubular housing 1, one end of which, B, is adapted to be inserted in the mouth. Mounted co-axially with housing I is a shaft 2 having loosely and rotatably mounted thereon a tapered bearing tube 5 carrying a propeller-like member 3 having blades 4. The propeller-like member 3 has a cup-like receptacle therein adapted to engage and hold a perforated capsule 6 containing finely divided medicament.
When end B of housing 1 is inserted in the mouth and air is inhaled through the mouth, the resulting airstream causes the propeller-like member 3 to rotate and precess about shaft 2 with the result that the finely owdered medicament is fluidized in capsule 6, is dispensed therefrom and passes with the airstream past blades 4 out of end B of housing 1 and into the mouth and respiratory tract of the user.
Referring now to FIG. 2, this form ofinhalation device comprises an housing of approximately circular cross-section having a diameter of about 1.9 cm. and length of about 5 cm. and comprising two engaging members 7 and 8, housing member 8 being adapted for insertion into the mouth and having passageways 9 therein to permit the passage of air. Mounted rigidly in and co-axially with housing member 8 is shaft 2 upon which is loosely and rotatably mounted tapered bearing tube 5 carrying propeller-like member 3 having blades 4. Propellerlike member 3 has a cup shaped receptacle adapted to receive and hold a capsule or container of finely powdered medicament 6 which is pierced with holes in the shoulder of the free end thereof. The tip 10 of shaft 2 is conical in shape, having a cone angle of about 30", and terminates in a substantially hemispherical portion having a diameter of about half the diameter of shaft 2.
Housing member 7 has in its end wall air passages 11 to permit the passage of air and constricting member 12 which serves to constrict the air stream through the device and thus increase its velocity past the capsule.
Through the end wall of housing member 7 extends locking member 13 which is attached at its outer end to base piece 14. Between base piece 14 and housing member 7 is a spring 15 which urges locking member 13 into a normally open position. Base piece 14 has a screw thread 16 which engages in a similar screw thread 18 in cap 17 (shown in FIG. 3) to hold locking member 14 in a closed position and to engage and hold capsule 6 mounted in the cup shaped member of propeller 3. When cap 17 is in position no air may be inhaled through the device and capsule 6 is firmly held in position. When cap 17 is removed from the device, spring 15 urges locking member 13 into its open position and air may be inhaled through the device with consequent rotation of propeller-like member 3 and dispersal of the finely powdered medicament from capsule 6.
Around locking member 13 is disc 19 which serves as a nonreturn valve for the device. Thus, if air is blown through the device disc 19 is urged against the end wall of housing 7 and closes air inlets l1 and thus prevents any further air from passing in that direction. If air is sucked through the device, disc 19 is urged away from the end wall of housing 7, freeing inlets l I and thus allowing air to pass through the device.
The whole device may be constructed of any suitable materials, preferably of a synthetic thermoplastic resin such as nylon in which case it may be made by an injection moulding technique. In order that the shaft 2 and bearing tube should be in rolling contact it is preferred to form tube 5 from an hard nylon and the shaft 2 from drawn wire.
As has been indicated above, the dimensions of the shaft and bearing affect the precise form of motion generated by the above device and that satisfactory operation may be achieved by many permutations of the dimension. It is preferred to ensure that the clearance between the shaft and the narrow end of the bearing is less than about five thousandths of an inch in order to minimize the effects which this clearance will have on the dominant motion generated by the clearance at the broad end of the bearing. Whilst it is generally preferred to use as thin a shaft as possible, a lower limit may be placed on the diameter of the shaft by rigidity considerations. In the present instance, the use of a drawn stainless steel shaft of uniform diameter of 0.080 inches and an hard nylon bearing with a top total clearance of 0.002 inches and a bottom total clearance of 0.016 inches between the shaft and the bearing wall is found to give a satisfactory form of motion. The bearing has a length of about 0.5 inches which gives an included angle for the frusto-cone of precession of approximately 2.
The forces acting on particles within the rotating capsule will vary with the diameter of the cone or frusto-cone of precession which itself varies along the length of the capsule. With the dimension given above, we have found that, for a capsule about 0.25 inches in diameter, satisfactory fluidization is achieved throughout the length of the capsule if the capsule is mounted with the base of its parallel walled portion about 0.2 inches from the top end of the bearing.
It is emphasized that the specific dimensions given above represent but one of the many possible permutations that may be made to obtain a device with essentially similar performance characterization.
In the device shown in FIG. 4 the shaft and bearing of the device of FIG. 2 have been transposed. The bearing tube 5a is mounted co-axially with the housing and shaft 2a is mounted on the lower end of the propellerlike device 3. Apart from this change, the construction and methods of use of the devices are similar. However, it is interesting to note that the transposed device generates an hypotrochoidal motion whereas the non-transposed version generates an epitrochoidal motion.
The cosistently effective administration of a powdered material by the device of FIG. 2 has been confirmed by experimental trials carried out using a bronchodilator as medicament in which the device was used to administer over 1,000 doses of bronchodilator to some 30 persons and the response determined spirometrically. Inadequate response in any single case was found to be due to lack of response to the medicament itself, as confirmed by administration by alternative routes. In all other cases the administration was found to be fully effective.
In the devices of FIGS. 1, 2, 3 and 4, the fact that there has been clearance at eachend of the bearing has enabled the shaft to lie across the bearing (rather than have to roll upon one wall of the bearing). The shaft has therefore contacted the bearing tube at the widest and narrowest parts only. FIG. 5 shows a further alternative form of bearing where lack of contact between the extremities of the bearing tube 5 is achieved by means of a lip 20 in the widest end of the bearing tube. This lip may be detachable e.g. by virtue of the fact that it is a snap fit into a co-operating recess in the bearing tube 5, or may be moulded integrally with the tube 5. The lip 20 may be made from the same material as the tube 5 or may be made from a friction pad material to assist rolling contact between the lip 20 and the shaft 2. In this latter case the tube may be made from a low friction material, such as polyfluorinated hydrocarbon resin, e.g. that sold under the Registered Trade Mark Teflon, in order to minimize the motion generated by the other end of the bearing tube.
FIG. 6 shows an alternative form of device which generates the motion of the method of the invention. This device comprises an elongated tubular housing in two snap fit parts 24 and 25. Mounted in part 25 by means of struts 26 is a ball race through which an air stream may pass by means of passages therethrough. In the ball race is journalled shaft 27 substantially co-axial with the housing. Shaft 27 is joined by a universal joint 28 to a shaft 29. Shaft 29 carries on its free end a boss 30 having a cup-like receptacle adapted to receive a powder capsule in a firm push fit. Between boss 30 and the universal joint 28, the shaft 29 is provided with an annular shoulder 31 having a rounded bearing face 32. The housing part 25 has mounted therein by struts 33 an annular bearing ring 34 around the inside surface of which bearing face 32 may run. There is sufficient clearance between the inside of ring 34 and shoulder 31 to permit the shaft 29 to be displaced through an extreme angle which corresponds with the desired included angle for the cone of precession. In order that slip between the face 32 and ring 34 should not occur to an appreciable extent, the ring 34 is made from a hard nylon and the shoulder 32 from hardened steel.
The vanes necessary to drive the shaft 29 may be mounted either upon the boss 30 as shown or upon either of shafts 27 and 29.
Part 24 of the housing may be provided with a construction 35.
An alternative form of the restraining bearing for the device of FIG. 6 is shown in FIG. 7. In this the annular shoulder 31 on shaft 29 is of greater diameter than ring 34 and is provided with a dependent skirt 36 whose inner face bears against the outer face of ring 34. It is interesting to note that this form of bearing produces an epitrochoidal motion, whereas the device of FIG. 6 gives an hypotrochoidal motion.
The device of FIG. 8 is essentially identical to that shown in FIG. 6 except that the pair of shafts 27 and 29 joined by the universal joint 28 are replaced by a single flexible shaft 37 of circular cross section which whips during rotation and thus permits the free end of the shaft 37 to rotate at an angle to the end of the shaft mounted in the ball race. As the speed of rotation of the shaft 37 increases the free end deflects further until the bearing face 32 of the shoulder 31 on the shaft 37 engages with annular bearing ring 34 and causes the rotating shaft to process at the desired rate. As indicated earlier, the shaft 37 may have a polygonal cross section, e.g. an hexagonal section. In such an instance the annular bearing ring 34 and the shoulder 31 may be dispensed with.
FIG. 9 shows a fonn of shaft and bearing wherein the concept of a tapered bearing tube is combined with the use of a restraining bearing ring.
This device comprises an elongated tubular housing 38 within which is mounted a short rigid cylindrical shaft 39 by means of struts 40. The free end of shaft 39 is indented with a conical recess 41. A rotatable boss 42 is mounted co-axially upon a short rigid cylindrical shaft 43 which is loosely journalled in the conical recess 41 in the end of shaft 39. The boss 42 is also provided with a dependent annular skirt 44 surrounding the shaft 43, which skirt has an internal diameter greater than the external diameter of shaft 39 and is of sufficient length that its internal surface may engage with the exterior of shaft 39.
Boss 42 is provided with vanes 45, which are adapted to cause rotation of the boss upon the passage of air through the device, and with a cup-like recess 46 adapted to receive a powder capsule in a push tight fit.
The housing 38 may be provided with an internal restriction 47 in order to increase the air flow rate past a capsule mounted in recess 46.
When air is passed through the device, boss 42 is caused to rotate, and in view of the loose mounting of the short shaft 43 in the recess 41, the inner face of skirt 44 is caused to bear against shaft 39. The contact between shaft 39 and skirt 44 causes the boss to precess around its axis of precession. Whilst this contact must be frictional, and preferably is a rolling contact, the contact between shaft 43 and recess 41 may be lubricated in order to assist free rotation of the shaft 43. I
FIG. shows a device wherein precession of the axis of rotation of the container is achieved other than by rolling contact between a rotating and a stationary member. Such a device comprises an elongated tubular housing 48 within the housing in a bearing bush 49 of cylindrical bore mounted by struts 50 substantially co-axially with the housing 48. Within bush 49 is mounted rotatable cylindrical shaft 51, which may be lubricated to assist its free rotation in the bush. The free end of shaft 51 carries a boss 52 provided with vanes 53. Off center on boss 52 is mounted a rigid cylindrical shaft 54 which carries a bearing tube 55 of cylindrical bore which may be lubricated to assist its free rotation upon shaft 54. The tube 55 carries a boss 56 provided with vanes 57 and with a receptacle 58, e. g. a cup shaped recess, adapted to receive a powder container in a push tight fit. The receptacle 58 is so orientated that a powder container is mounted upon boss 56 at an angle to the axis of tube 55.
If desired the housing 48 may be provided with a venturi 59 or any of the other further features provided in the device of FIG. 2 in order to optimize its operation.
The passage of air through the device causes boss 52 to be rotated, thus causing shaft 54 to precess about the axis of shaft 51; and causes boss 56 to rotate which means that a container mounted thereon is caused to rotate about an axis which is inclined to shaft 54 and is precessing by virtue of the rotation of boss 52.
It will be appreciated that the device of FIG. 10 may be modified by mounting shaft 54 with its axis intersecting the axis of shaft 51, i.e. at an angle thereto. The receptacle 58 in the boss 56 may then be orientated so that a powder container is mounted therein co-axially with tube 55 rather than at an angle thereto.
in both the above forms of the device of FIG. 10, each shaft and bearing may be lubricated in order to assist the rotation thereof.
1. A method for dispensing a particulate medicament from a container, which comprises placing a container provided with at least one powder outlet on one end of a rotatable member, supporting the rotatable member only at the other end a bearing means so shaped as to give to the axis of rotation of said rotatable member during rotation of the rotatable member a path of precession which is contained within the generally conical surface of precession and maintaining the axis of rotation of the container at an angle to the axis of the generally conical surface of precession while leaving the said one end of the rotatable member free, and pneumatically rotating said rotatable member for rotating the container about an axis of the container for causing the walls of the container to undergo repeated changes in radial acceleration with respect to the generally conical surface of precession, which changes of acceleration are of sufficient magnitude to overcome the centrifugal and cohesive forces which hold the particles in place upon the wall of the container.
2. A method as claimed in claim 1 wherein the included angle of the generally conical surface of precession is from W to 60.
3. A method as claimed in claim 2 wherein the included angle is from 1 to 5 4. A method as claimed in claim 1 wherein the effective motion of a point on the container wall is a circular sequence of cusps leading into one another at nodes, and the number of said nodes occurring per rotation of the container axis about the axis of the generally conical surface of precession is from 2 to 25.
5. A method as claimed in claim 4 wherein the number of nodes is from 3 to 10.
6. A device for dispensing a particulate medicament material from a container, comprising a rotatable member having a free end and said free end having means to receive the container, two cooperating bearing means, one bearing means being a shaft and the other being at least one bearing member within which said shaft is journalled, one of said bearing means being on the end of said rotatable member opposite said free end and the other bearing means being fixed, said shaft and said bearing member providing the sole support for said rotatable member and being so shaped as to give the axis of rotation of said rotatable member during rotation of the rotatable member a path of precession which is contained within a generally conical surface of precession and maintaining the axis of rotation of said rotatable member at an angle to the axis of the generally conical surface of precession, and means associated with said rotatable member for pneumatically rotating it.
7. A device as claimed in claim 6 further comprising an elongated tubular housing within which the rotatable member and the shaft and bearing member are mounted, one of said shaft and bearing member being rigidly mounted substantially co-axially with the housing.
8. A device as claimed in claim 6 wherein the shaft and bearing member are in frictional contact.
9. A device as claimed in claim 6 wherein the rotatable member has at least one vane thereon for rotating the member upon the passage of a gas stream through the device.
10. A device as claimed in claim 6 which comprises a rotatable shaft mounted in a stationary bearing member, the free end of said shaft carrying a universal joint, a further shaft connected to said first shaft by means of said universal joint whereby the free end of said further shaft may be displaced during rotation thereof at an angle about the axis of said stationary bearing member, the free end of said further shaft carrying means to receive a container, a stationary annular bearing member loosely encircling said further shaft, said annular bearing member and a portion of said further shaft contacting one another in a frictional contact during rotation of said further shaft.
11. A device as claimed in claim 10 wherein said further shaft and said stationary annular bearing member contact one another in a rolling contact at substantially all times during operation of the device.
12. A device as claimed in claim 6 in which the bearing member has an annular bearing surface and the shaft is journalled loosely in the bearing member, one of said shaft and said bearing being stationary, the other being on the rotatable member to be rotated by the pneumatic rotating means, the rotatable member being capable of being displaced during rotation thereof at an angle about the axis of the stationary member, the annular bearing surface of the bearing member and at least a portion of the shaft contacting one another in frictional contact during rotation of the rotatable member.
13. A device as claimed in claim 12 wherein the bearing member is a bearing tube contacting the shaft at both ends of the bearing tube.
14. A device as claimed in claim 13 wherein the shaft is a rigid substantially uniformly cylindrical shaft and the bearing tube is an internally tapered bearing tube.
15. A device as claimed in claim 13 wherein the bearing tube has annular ridges at at least one end thereof, said ridges providing an annular bearing surface against which the shaft bears.
16. A device as claimed in claim 13 wherein the diameter of the shaft and the internal diameter of the bearing tube at the contact between that end of the bearing tube and the shaft generating the non-dominant motion number for the nondominant motion of a point on the container wall will have a value in excess of 15.
a/h (R /Rr) R, and the term exceeds the term R by a sufficient amount of achieve fluidization of powder within a container mounted in the device, and wherein a is the distance of the base'of the parallel walled section of the container wall from the. non-dominant contact between the shaft and bearing tube, h is the distance between the dominant and non-dominant contacts between shaft and bearing tube, R is the internal radius of the bearing tube at the dominant contact, r is theradius of the shaft and R is the in-' ternal radius of the container at the base of the parallel walled section of the container wall.
19. A device as claimed in claim 13 in which a shaft is rotatably journalled in a stationary bearing tube and there is a dominant contact-and a non-dominant contact between the shaft and bearing tube, the dominant contact being a rolling contact, the dimensions of the bearing tube and the shaftbeing in the relationship 7 a/lz (FIR- r) R and the term a/h (r"/R-r) exceeds the term R by a sufficient amount to achieve fluidization ofpowder within a container mounted in the device; and wherein a is the distance of the base of the parallel walled section of the container wall from the non-dominant contact between the shaft and bearingtube, h is the distance between the dominant and non-dominantcontacts between the shaft and bearing tube, R is the internal radius of the bearing tube at the dominant contact, r is the radius of the shaft and R is the internal radius of the container at the base of the parallel walled section of the container.
20. A device as claimed in claim 12 wherein the shaft is the stationary member and the bearing member is the rotatable member.
21. A device as claimed in claim 12 in which the shaft is a rigid substantially uniform cylindrical shaft and the bearing member is an internally tapered rotatable bearing tube which has an internal diameter at that end at which the free end of the shaft is positioned which is smaller than the internal diameter at its outer end.
22. A device as claimed in claim 21 wherein the bearing tube has an internal diameter at the inner end which is from 1.5 to 6.0 percent greater than the diameter of the shaft and an internal diameter at the outer end which is equal to the diameter of the shaft plus from 1.3 to 3.5 percent of the internal length of the bearing tube.
23v A device as claimed in claim 22 wherein the bearing tube has an internal length of from 4 to 10 times the diameter 'of the shaft.
24. A device as claimed in claim 11 wherein the shaft and bearing member contact one another in a rolling contact at substantially all times during operation of the device.
25. A device as claimed in claim 6 further comprising a powder capsule mounted upon the rotatable member.