Method and apparatus for filling containers

Information

  • Patent Grant
  • 6820658
  • Patent Number
    6,820,658
  • Date Filed
    Friday, April 4, 2003
    21 years ago
  • Date Issued
    Tuesday, November 23, 2004
    19 years ago
Abstract
A filling apparatus for, a filling system for and a method of introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propellant under pressure, the filling apparatus comprising: a main body (4) including a passageway (20) for communicating, in use, with a valve stem (144) extending from a head (141) of a body (139) of a container (138), the container (138) comprising a metering chamber (143) selectively communicatable by the valve stem (144) with the atmosphere and a storage chamber (140) defined by the body (139); a fill actuator (7) comprising a filling valve assembly (29) in communication with the passageway (20) for selectively introducing thereinto propellant under pressure containing a substance in a suspension or solution; an exhaust actuator (10) comprising an exhaust valve assembly (48) in communication with the passageway (20) for selectively exhausting therefrom propellant under pressure containing substance; and a container-engaging body (16) in communication with the passageway (20) for receiving, in use, the head (141) of the body (139) of the container (138), the container-engaging body (16) being movable relative to the main body (4) so as thereby to cause the valve stem (144) of the container (138) to be selectively positioned in an extended closed position, a depressed open position or an intermediate position therebetween, in which intermediate position the metering chamber (143) of the container (138) is closed to the atmosphere.
Description




The present invention relates to a filling apparatus for, a filling system for and a method of introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propellant under pressure. Most particularly, the present invention relates to a filling head included in a line in which a propellant under pressure containing a substance in a suspension or solution is circulated, with the filling head being brought into and out of communication with containers to be filled.




BACKGROUND OF THE INVENTION




Containers for holding a suspension or solution of a pharmaceutical substance in a propellant under pressure are well known. One such known container comprises a body which defines a storage chamber, a valve stem which extends from a head of the body and a metering chamber which is selectively communicatable by the valve stem with the atmosphere and the storage chamber; the valve stem providing, via an L-shaped conduit which extends between the free end and the side wall thereof, the outlet of the container through which metered doses of propellant containing pharmaceutical substance are delivered. The valve stem is axially displaceable between a first, extended position in which the metering chamber, and hence the container, is closed to the atmosphere since the L-shaped conduit is disposed wholly outside the metering chamber, and a second, depressed position, in which the metering chamber is in communication with the outlet provided by the L-shaped conduit in the valve stem and through which a metered dose of propellant containing pharmaceutical substance is delivered. The container is filled with the valve stem in the depressed position, with the propellant containing pharmaceutical substance being forced downwardly through the L-shaped conduit in the valve stem, through the metering chamber and into the storage chamber defined by the body of the container.




EP-A-0419261 discloses a filling system for introducing into a container a suspension or solution of a pharmaceutical substance in a propellant under pressure, which filling system includes a filling apparatus that prevents the escape of pharmaceutical substance into the atmosphere. In this filling system the filling apparatus is configured to be flushed by a volume of high pressure propellant while still in fluid communication with the container so that the propellant under pressure containing pharmaceutical substance which is remaining in the filling apparatus after filling the container with the same is flushed through into the container prior to withdrawal of the filling apparatus from the container. This configuration does, however, require additional propellant to be introduced into the container to achieve the flush. Moreover, following the flushing action, propellant under pressure present in the valve stem can escape to the atmosphere.




SUMMARY OF THE INVENTION




The present invention in at least one preferred aspect aims to provide an improved filling apparatus which at least partially overcomes the above-mentioned problems.




The present invention also aims to provide a method and filling system which are configured to fill a container without requiring the release of propellant alone or propellant containing pharmaceutical substance directly to the atmosphere.




The present invention provides a filling apparatus for introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propellant under pressure, comprising: a main body including a passageway for communicating, in use, with a valve stem extending from a head of a body of a container, the container comprising a metering chamber selectively communicatable by the valve stem with the atmosphere and a storage chamber defined by the body; a fill actuator comprising a filling valve assembly in communication with the passageway for selectively introducing thereinto propellant under pressure containing a substance in a suspension or solution; an exhaust actuator comprising an exhaust valve assembly in communication with the passageway for selectively exhausting therefrom propellant under pressure containing substance; and a container-engaging body in communication with the passageway for receiving, in use, the head of the body of the container, the container-engaging body being movable relative to the main body so as thereby to cause the valve stem of the container to be selectively positioned in an extended closed position, a depressed open position or an intermediate position therebetween, in which intermediate position the metering chamber of the container is closed to the atmosphere.




Preferably, the filling apparatus further comprises biasing means for biasing the container-engaging body away from the main body.




More preferably, the biasing means comprises at least one compression spring disposed between the main body and the container-engaging body.




Preferably, the main body includes an outwardly-extending part through which the passageway extends and which is sealingly received within a bore in the container-engaging body.




More preferably, the filling apparatus further comprises an annular seal disposed at the distal end of the outwardly-extending part of the main body, which seal is, in use, abutted by the distal end of the valve stem of the container.




Preferably, the container-engaging body includes a chamber of greater radial dimension than the valve stem of the container into which, in use, extends the valve stem of the container and a conduit in communication with the chamber for feeding a pressurised fluid thereto.




Preferably, the container-engaging body includes an annular seal disposed about a lower end of the chamber against which, in use, is abutted the head of the body of the container which surrounds the valve stem thereof. More preferably, the annular seal comprises an O-ring.




Preferably, opposing surfaces of the main body and the container-engaging body include one or the other of at least one projection and at least one recess, whereby, when the main body and the container-engaging body are moved together, the at least one projection is engaged within the at least one recess.




The present invention also extends to a filling system for introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propellant under pressure incorporating the above-described filling apparatus.




The present invention further provides a method of introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propellant under pressure, comprising the steps of: providing a container comprising a body defining a storage chamber, a valve stem extending from a head of the body and a metering chamber selectively communicatable by the valve stem with the atmosphere and the storage chamber, the valve stem having an outlet opening and a inlet opening and being movable between an extended closed position in which the inlet opening is located outside the body and a depressed open position in which the inlet opening is located within the body; communicating the outlet opening of the valve stem of the container with a passageway in a main body of a filling apparatus, the filling apparatus comprising a fill actuator comprising a filling valve assembly for selectively introducing into the passageway propellant under pressure containing a substance, in particular a pharmaceutical substance, in a suspension or solution and an exhaust actuator comprising an exhaust valve assembly for selectively exhausting from the passageway propellant under pressure containing substance; depressing the valve stem of the container so as to provide a communication path to the storage chamber thereof; opening the filling valve assembly thereby to fill the storage chamber of the container with propellant under pressure containing a substance, in particular a pharmaceutical substance, in a suspension or solution; closing the filling valve assembly; moving the valve stem of the container to an intermediate position between the depressed open position and the extended closed position, in which intermediate position the metering chamber of the container is closed to the atmosphere and the inlet opening in the valve stem of the container is located outside the body thereof; and opening the exhaust valve assembly to enable propellant under pressure containing substance in the passageway and the valve stem of the container to exhaust.




Preferably, the filling apparatus further comprises a container-engaging body which is movably disposed to the main body thereof and is configured to receive the head of the body of the container which includes the valve stem, and the method further comprises the step of biasing the container-engaging body away from the main body of the filling apparatus.




More preferably, the main body of the filling apparatus includes an outwardly-extending part through which the passageway extends and which is sealingly received within a bore in the container-engaging body.




Still more preferably, the method further comprises the step of sealing the distal end of the outwardly-extending part of the main body against the distal end of the valve stem of the container.




Preferably, the method further comprises the step of surrounding the part of the valve stem of the container which includes the inlet opening and extends from the body of the container with a pressurised fluid at least when the exhaust valve assembly is opened to exhaust propellant under pressure containing substance from the passageway and the valve stem of the container.




Preferably, the pressurised fluid is at a pressure greater than the vapour pressure of the propellant under pressure containing substance.




In a preferred embodiment the fluid is a gas. Preferably, the gas is one of air or nitrogen.











BRIEF DESCRIPTION OF THE DRAWINGS




A preferred embodiment of the present invention will now be described hereinbelow by way of example only with reference to the accompanying drawings, in which:





FIG. 1

illustrates a part-sectional side view of a filling head in accordance with a preferred embodiment of the present invention;





FIG. 2

illustrates a vertical sectional view (along section A—A) of the filling head of

FIG. 1

;





FIG. 3

illustrates a horizontal sectional view (along section B—B) of the filling head of

FIG. 1

;





FIG. 4

illustrates an underneath plan view of the filling head of

FIG. 1

;





FIG. 5

illustrates an end view of the filling head of

FIG. 1

, illustrated with part of the housing of the exhaust actuator removed;





FIG. 6

illustrates a schematic representation of a filling system in accordance with a preferred embodiment of the present invention for introducing into a container a suspension or solution of a pharmaceutical substance in a propellant under pressure, with the system incorporating the filling head of

FIG. 1

; and





FIGS. 7

to


13


illustrate enlarged part-sectional side views of part of the filling head of

FIG. 1

in a series of respective positions representing successive sequential steps in a container filling operation.











DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS





FIGS. 1

to


5


illustrate a filling head


2


in accordance with a preferred embodiment of the present invention.




The filling head


2


comprises a main body


4


which includes a downwardly-extending part


5


that extends from a lower surface


6


thereof, a fill actuator


7


disposed to one lateral side of the main body


4


and an exhaust actuator


10


disposed to the opposite lateral side of the main body


4


. The filling head


2


further comprises an actuating mandrel


14


disposed to and above the main body


4


by which the filling head


2


is moved vertically. The filling head


2


still further comprises a slide body


16


for receiving a container to be filled which is mounted to the downwardly-extending part


5


of the main body


4


so as to be vertically movable relative thereto.




The main body


4


includes a vertically-oriented passageway


20


which is located substantially centrally therein and includes first and second horizontally-opposed openings


21


,


22


at the upper end


24


thereof and a third opening


25


at the lower end


26


thereof which is located in the downwardly-extending part


5


. The first and second openings


21


,


22


communicate respectively with the fill actuator


7


and the exhaust actuator


10


.




The fill actuator


7


comprises a housing


28


and a filling valve assembly


29


which is movably disposed thereto. The filling valve assembly


29


comprises a filling valve stem


30


which is slideably disposed within an annular chamber


31


in the main body


4


and includes a valve sealing end


32


which seals against a valve seat


33


that defines the first opening


21


of the passageway


20


in the main body


4


. The chamber


31


includes an inlet conduit


34


and an outlet conduit


35


formed in the main body


4


on opposing lateral sides of the chamber


31


. The filling valve assembly


29


further comprises a reciprocally movable filling valve member


36


which is axially coupled to the filling valve stem


30


and is sealingly disposed within an annular chamber


37


defined in the housing


28


. The filling valve member


36


includes a radially outwardly-extending part


38


which sealingly divides the chamber


37


into first and second chamber parts


39


,


40


, the first chamber part


39


being near to the filling valve stem


30


and the second chamber part


40


being remote from the filling valve stem


30


. The housing


28


includes a conduit


41


which communicates with the second chamber part


40


of the chamber


37


and is for connection to a source of a pressurised fluid. The filling valve assembly


29


yet further comprises biasing means


42


, in this embodiment a compression spring, for biasing the filling valve member


36


and hence the filling valve stem


30


into the chamber


31


in the main body


4


. The application/withdrawal of fluid pressure via the conduit


41


introduces/withdraws fluid from the second chamber part


40


of the chamber


37


, thereby causing sliding movement of the filling valve member


36


in the chamber


37


, and thereby sliding movement of the filling valve stem


30


in the chamber


31


. In this way, the valve sealing end


32


of the filling valve stem


30


can be moved into and out of engagement with the valve seat


33


that communicates with the first opening


21


of the passageway


20


in the main body


4


. The chamber


31


is sealed at the end thereof remote from the valve seat


33


and at the junction of the filling valve member


36


and the filling valve stem


30


by a flexible annular seal


43


that surrounds the filling valve stem


30


.




The exhaust actuator


10


comprises a valve block


44


which is disposed in a cavity


45


in the main body


4


, a housing


46


which is connected to the valve block


44


and an exhaust valve assembly


48


which is movably disposed within the housing


46


.




The housing


46


comprises an annular support sleeve


49


and the exhaust valve assembly


48


comprises an exhaust valve stem


50


which includes a valve sealing end


51


and is slideably disposed in the support sleeve


49


. The exhaust valve stem


50


is generally conical in shape, and increases in diameter away from the valve sealing end


51


. In this embodiment the exhaust valve stem


50


includes a peripheral ridge


52


which acts to reduce the retention of substance thereon. The exhaust valve assembly


48


further comprises a reciprocally movable exhaust valve member


54


which is axially coupled to the exhaust valve stem


50


and is sealingly disposed within an annular chamber


56


in the support sleeve


49


. The exhaust valve member


54


includes a radially outwardly-extending central part


58


which sealingly divides the chamber


56


into first and second chamber parts


60


,


62


, the first chamber part


60


being near to the exhaust valve stem


50


and the second chamber part


62


being remote from the exhaust valve stem


50


. The support sleeve


49


includes first and second conduits


64


,


66


for connection to a source of a pressurised fluid, each conduit


64


,


66


communicating with a respective one of the first and second chamber parts


60


,


62


of the chamber


56


. Application of fluid pressure via one of the conduits


64


,


66


introduces fluid into a respective one of the first and second chamber parts


60


,


62


of the chamber


56


, thereby causing sliding movement of the exhaust valve member


54


in the chamber


56


, and thereby sliding movement of the exhaust valve stem


50


in the support sleeve


49


. In this way, the valve sealing end


51


of the exhaust valve stem


50


can be moved into and out of engagement with an exhaust valve seat


67


provided by the valve block


44


. The housing


46


further includes a generally annular chamber


70


in which the support sleeve


49


and the exhaust valve stem


50


are located, with the part of the chamber


70


surrounding the generally conical exhaust valve stem


50


also being generally conical. The housing


46


yet further comprises an exhaust tube


71


which is disposed to a side thereof remote from the valve block


44


and communicates with the chamber


70


.




The valve block


44


includes a conical recess


72


which is an extension of the chamber


70


in the housing


46


and at the bottom of which is the exhaust valve seat


67


. The valve block


44


further includes a fluid passageway


73


therein which includes a first, inlet opening


74


which communicates with the second opening


22


of the passageway


20


in the main body


4


and a second, outlet opening


75


at the exhaust valve seat


67


.




In order to provide the required mounting for the support sleeve


49


, the chamber


70


in the housing


46


is divided into three arcuate chamber parts


78


,


80


,


82


in the vicinity of the mounting of the exhaust valve assembly


48


(as illustrated in FIG.


5


). In this embodiment the three arcuate chamber parts


78


,


80


,


82


are substantially equal in circular length.




The chamber


70


is configured principally to be exhausted with an exhaust gas passing from the valve block


44


. In this embodiment the valve block


44


includes a plurality of first exhaust gas inlet passages


84


which surround the outlet opening


75


at the exhaust valve seat


67


. The first exhaust gas inlet passages


84


include respective outlets


86


which define an array, preferably a circular array, around the exhaust valve seat


67


, with the array being axially centred on a common axis of the exhaust valve stem


50


, the exhaust valve seat


67


and the passageway


73


. At least those portions of the first exhaust gas inlet passages


84


which define the outlets


86


are parallel to the passageway


73


. In this embodiment the outlets


86


are formed in the surface of the conical recess


72


in the valve block


44


and are located downstream, with reference to the direction of flow through the chamber


70


, of the outlet opening


75


of the passageway


73


. The valve block


44


further includes an annular chamber


88


in an outer surface thereof which commonly connects the first exhaust gas inlet passages


84


and which is in communication with a conduit


90


in the main body


4


for supplying a source of an exhaust gas thereto. In this embodiment the conduit


90


is directed radially to the annular chamber


88


, but in an alternative embodiment could be directed tangentially.




The chamber


70


is further configured to be exhausted with an exhaust gas passing through the housing


46


. In this embodiment the housing


46


includes a plurality of second and third exhaust gas inlet passages


92


,


93


downstream of the first exhaust gas inlet passages


84


. The second and third exhaust gas inlet passages


92


,


93


include respective outlets


94


,


95


which define an array, preferably a circular array, around the exhaust valve seat


67


and communicate with the chamber


70


. At least those portions of the second and third exhaust gas inlet passages


92


.


93


which include the outlets


94


,


95


are parallel to the first exhaust gas inlet passages


84


, and thus also parallel to the passageway


73


in the valve block


44


. The housing


46


includes an annular chamber


96


which commonly connects the second and third exhaust gas inlet passages


92


,


93


and a conduit


98


in communication with the chamber


96


for supplying a source of an exhaust gas thereto.




The slide body


16


is mounted for vertical sliding movement relative to the main body


4


by first and second spaced biasing elements


100


, in this embodiment compression springs, disposed therebetween. Each of the biasing elements


100


is mounted on a respective threaded member


102


, both of which threaded members


102


connect the slide body


16


to the main body


4


. In the normal or inoperative configuration, the slide body


16


is biased by the biasing elements


100


downwardly away from the main body


4


so as to be separated therefrom by a gap


103


.




The slide body


16


includes a bore


104


for slideably receiving in mating relationship the downwardly-extending part


5


of the main body


4


. The slide body


16


further includes a projection


105


on the upper surface


106


thereof which is complementary to a corresponding recess


107


formed in the lower surface


6


of the main body


4


around the downwardly-extending part


5


. The bore


104


includes an annular seal


109


which surrounds the downwardly-extending part


5


so as to form a fluid tight seal therebetween. The lower, distal end


110


of the downwardly-extending part


5


is provided thereunder with an annular valve stem seal


112


which includes a central opening


113


which is aligned with the passageway


20


in the main body


4


, the inner and outer diameters of the valve stem seal


112


substantially corresponding respectively to the inner diameter of the third opening


25


in the passageway


20


and the inner diameter of the bore


104


. The bore


104


defines a chamber


116


which is configured to have an inner diameter that is larger than the outer diameter of the valve stem of the container to be filled. The chamber


116


includes a main, upper section


122


and lower section


123


which is of slightly smaller diameter than the upper section


122


and defines an opening


124


through which the valve stem of the container to be filled extends. The slide body


16


yet further includes a conduit


126


which is in communication with the chamber


116


. The slide body


16


further comprises an annular head seal


131


which is located below and surrounds the opening


124


to the chamber


116


. The head seal


131


is retained in a central opening


133


in a seal retaining block


132


which provides the lower part of the slide body


16


. The seal retaining block


132


includes a downwardly-extending recess


134


in a lower surface


135


thereof for receiving the head of a container to be filled.




As illustrated in

FIG. 7

, in this embodiment a container


138


to be filled by the filling head


2


comprises a body


139


which defines a storage chamber


140


for holding a suspension or solution of a pharmaceutical substance in a propellant under pressure. The body


139


includes a head


141


which includes a peripheral housing


142


that defines a metering chamber


143


and a valve stem


144


that is movably disposed in the housing


142


and extends from the head


141


. The valve stem


144


is movable between an extended position (as illustrated in

FIG. 7

) and a depressed position (as illustrated in FIG.


8


), the valve stem


144


normally being biased by a compression spring


145


into the extended position. The valve stem


144


includes an L-shaped conduit


146


which extends between a first, outlet opening


147


located at the distal end of the valve stem


144


and a second, inlet opening


148


located in the lateral wall of the valve stem


144


. The valve stem


144


further includes a U-shaped conduit


151


in that part thereof which is always disposed within the container


138


. The U-shaped conduit


151


includes first and second axially-spaced openings


153


,


155


located in the lateral wall of the valve stem


144


and enables communication between the metering chamber


143


and the storage chamber


140


of the container


138


via bores


156


in the housing


142


.




When the valve stem


144


is in the extended position (as illustrated in FIG.


7


), the inlet opening


148


of the L-shaped conduit


146


is located outside the body


139


of the container


138


, and in particular remote from the metering chamber


143


within the container


138


. Thus, when the valve stem


144


is in the extended position, the container


138


is closed since there is no communication path between the storage chamber


140


and the L-shaped conduit


146


in the valve stem


144


. In the extended position, the U-shaped conduit


151


communicates via the first opening


153


and the bores


156


in the housing


142


with the storage chamber


140


and via the second opening


155


with the metering chamber


143


. In this position, with the container


138


inverted, the metering chamber


143


is filled.




When the valve stem


144


is in the depressed position (as illustrated in FIG.


8


), that is, one of either a fill position or a discharge position, the valve stem


144


is pushed down against the biasing action of the biasing element


145


, thereby to move the inlet opening


148


of the L-shaped conduit


146


into communication with the metering chamber


143


and the U-shaped conduit


151


out of communication with the metering chamber


143


and solely in communication with the storage chamber


140


via the bores


156


in the housing


142


. In a filling operation, a solution or suspension of a pharmaceutical substance in a propellant under pressure is forced downwardly through the L-shaped conduit


146


, through the metering chamber


143


and into the storage chamber


140


of the container


138


by being forced past an annular seal


166


which surrounds the valve stem


144


at the bottom of the metering chamber


143


. During the discharge of a metered volume of a suspension or solution of a pharmaceutical substance in propellant under pressure from the container


138


, the metered volume of suspension or solution present in the metering chamber


143


is permitted to flow outwardly through the L-shaped conduit


146


by the provision of a communication path between the metering chamber


143


and the inlet opening


148


of the L-shaped conduit


146


. In the discharge operation, the seal


166


prevents any further of the suspension or solution in the storage chamber


140


from entering the metering chamber


143


so that a precise volume is discharged.




In this embodiment the principal structural components of the filling head


2


are typically composed of stainless steel and the seals are typically composed of nitrile rubber. The only exceptions are the diaphragm seals and the seals which come into contact with propellant which typically are composed of PTFE and the valve block


44


and the exhaust valve stem


50


which are typically composed of hardened stainless steel.





FIG. 6

illustrates a filling system which incorporates the above-described filling head


2


for filling a container


138


with a metered volume of a suspension or solution of a pharmaceutical substance in a propellant under pressure.




The filling head


2


is included in a circulatory line, designated generally by reference sign


170


, in which a propellant under pressure containing a pharmaceutical substance in a suspension or solution is circulated. The circulatory line


170


includes a mixing vessel


172


which holds propellant containing pharmaceutical substance in a suspension or solution. The mixing vessel


172


is pressurised, as is the remainder of the circulatory line


170


, so that the propellant is not only under pressure, but is also maintained as a liquid where the boiling point of the propellant is lower than the ambient temperature. A line


176


connects an outlet


174


of the mixing vessel


172


to a pump


178


, which pump


178


is provided to pump propellant around the circulatory line


170


. Another line


180


connects the pump


178


to the inlet side of an inlet valve


182


. A further line


183


connects the outlet side of the inlet valve


182


to a metering chamber


184


. The metering chamber


184


is configured to receive a metered volume of the propellant containing pharmaceutical substance in a suspension or solution on opening of the inlet valve


182


. The metered volume corresponds to the volume which is required to be introduced into the container


138


by the filling head


2


. A yet further line


186


connects the metering chamber


184


to the filling head


2


, specifically the inlet conduit


34


in the main body


4


of the filling head


2


. As described hereinabove, the inlet conduit


34


communicates with the chamber


31


surrounding the filling valve stem


30


and thence with the outlet conduit


35


. A still further line


188


connects the filling head


2


, specifically the outlet conduit


35


in the main body


4


of the filling head


2


, to the inlet side of an outlet valve


190


. A still yet further line


192


connects the outlet side of the outlet valve


190


to an inlet


194


of the mixing vessel


172


, thereby completing the circulatory line


170


. The filling system further includes a bypass valve


196


which is provided in a line


198


connected between the inlet side of the inlet valve


182


and the outlet side of the outlet valve


190


.




The operation of the filling head


2


in filling a container


138


with a metered volume of a suspension or solution of a pharmaceutical substance in a propellant under pressure and subsequently exhausting residual propellant under pressure containing pharmaceutical substance will now be described hereinbelow with reference to

FIGS. 6

to


13


.




In a first step, as illustrated in

FIG. 7

, the head


141


of a container


138


to be filled is located within the downwardly-extending recess


134


in the seal retaining block


132


of the slide body


16


. In this position, the head


141


of the container


138


bears against the head seal


131


and the distal end of the valve stem


144


of the container


138


bears against the valve stem seal


112


, with the valve stem


144


being urged into the extended position by the biasing element


145


. In this way, the chamber


116


is sealed by the valve stem and head seals


112


,


131


. Although not illustrated, it will be understood that the bottom of the container


138


is supported and urged upwardly. Further, in this position, the biasing elements


100


urge the slide body


16


away from the main body


4


so as to provide the gap


103


therebetween, and both the filling valve assembly


29


and the exhaust valve assembly


48


are closed.




In a second step, as illustrated in

FIG. 8

, the actuating mandrel


14


is operated upon to move the main body


4


and both the fill actuator


7


and the exhaust actuator


10


disposed thereto downwardly relative to the slide body


16


against the bias of the biasing elements


100


. This movement causes the projection


105


to pass into the recess


107


and the gap


103


to be closed. Additionally, the downwardly-extending part


5


of the main body


4


is urged via the valve stem seal


112


against the distal end of the valve stem


144


of the container


138


, thereby to push the valve stem


144


downwardly to the depressed open position in which the inlet opening


148


of the L-shaped conduit


146


in the valve stem


144


is in communication with the metering chamber


143


of the container


138


and the U-shaped conduit


151


in the valve stem


144


is located solely in communication with the storage chamber


140


of the container


138


and out of communication with the metering chamber


143


.




In a third step, as illustrated in

FIG. 9

, the filling valve assembly


29


is opened by retracting the valve sealing end


32


of the filling valve stem


30


from the valve seat


33


. A metered volume of propellant containing pharmaceutical substance in suspension or solution present in the metering chamber


184


is then introduced through the inlet conduit


34


, through the annular chamber


31


, through the passageway


20


, through the L-shaped conduit


146


in the valve stem


144


, through the metering chamber


143


of the container


138


and finally past the seal


166


into the storage chamber


140


of the container


138


via the bores


156


in the housing


142


.




Prior to opening of the filling valve assembly


29


, the inlet valve


182


and the outlet valve


190


in the circulatory line


170


are closed. When the inlet valve


182


and the outlet valve


190


are closed, the line


183


connecting the inlet valve


182


to the metering chamber


184


, the metering chamber


184


, the line


186


connecting the metering chamber


184


to the filling head


2


and the line


188


connecting the filling head


2


to the inlet side of the outlet valve


190


are full of propellant containing pharmaceutical substance in suspension or solution. When the metering chamber


184


is emptied a volume of propellant under pressure containing pharmaceutical substance corresponding to that metered by the metering chamber


184


is passed through the line


186


and into the filling head


2


through the inlet conduit


34


. In this way, a precisely metered volume of propellant containing pharmaceutical substance in suspension or solution is introduced into the container


138


. In order that the pump


178


can continue to operate continuously, thereby continuing to circulate the propellant containing pharmaceutical substance around the circulatory line


170


, when the inlet valve


182


and the outlet valve


190


are closed, the bypass valve


196


is open.




In a fourth step, as illustrated in

FIG. 10

, after a metered volume of propellant containing pharmaceutical substance in suspension or solution has been introduced into the container


138


, the filling valve assembly


29


is closed by biasing the valve sealing end


32


of the filling valve stem


30


against the valve seat


33


. Thereafter, two separate operations are commenced in order to obviate the inadvertent release of propellant containing pharmaceutical substance into the atmosphere at the end of the filling operation.




In a first operation a pressurized fluid is supplied to the conduit


126


in the slide body


16


. This fluid provides a sealing jacket in the chamber


116


and the space


167


defined between the inner circumference of the head seal


131


and the lateral wall of the valve stem


144


of the container


138


. This fluid is supplied at a pressure higher than the vapour pressure of the propellant under pressure containing pharmaceutical substance which remains in the passageway


20


in the main body


4


and the valve stem


144


of the container


138


. In a preferred embodiment the fluid is a gas. Preferably, the gas is one of air or nitrogen.




In a second operation an exhaust gas, preferably one of air or nitrogen, is introduced under pressure into the chamber


70


in the exhaust actuator


10


via the first, second and third exhaust gas inlet passages


84


,


92


,


93


. The exhaust gas is preferably heated to a temperature of at least about 35° C., more preferably from 35 to 50° C., in order to prevent any of the propellant containing pharmaceutical substance which is exhausted through the chamber


70


from re-liquefying therein. Typically, where air is used as the exhaust gas, the mass flow rate is in the range of from 0.1 to 10 grams/second, preferably around 2 grams/second.




In a fifth step, as illustrated in

FIG. 11

, the actuating mandrel


14


is partially raised thereby partially releasing the valve stem


144


of the container


138


to an intermediate position between the extended closed position (as illustrated in

FIG. 7

) and the depressed open position (as illustrated in FIG.


8


). In this intermediate position, the inlet opening


148


of the L-shaped conduit


146


in the valve stem


144


of the container


138


is raised so as not to be in communication with the metering chamber


143


of the container


138


but with the space


167


defined between the inner circumferential surface of the head seal


131


and the lateral wall of the valve stem


144


of the container


138


and the chamber


116


in communication therewith. The propellant under pressure containing pharmaceutical substance which is present in the L-shaped conduit


146


in the valve stem


144


and the passageway


20


in the main body


4


is prevented from escaping therefrom via the inlet opening


148


in the valve stem


144


as a result of the overpressure of the fluid supplied via the conduit


126


. Thus, following the filling operation, and while the valve stem


144


of the container


138


is still in communication with the filling head


2


, the provision of a sealing jacket of a pressurised fluid around the part of the valve stem


144


which includes the L-shaped conduit


146


prevents the propellant under pressure containing pharmaceutical substance which remains in the L-shaped conduit


146


in the valve stem


144


and the passageway


20


in the main body


4


from escaping through the inlet opening


148


in the valve stem


144


, which propellant containing pharmaceutical substance would otherwise be subsequently released to the atmosphere following the removal of the container


138


from the filling head


2


.




When the valve stem


144


is in this intermediate position, the metering chamber


143


of the container


138


is closed to the atmosphere since the L-shaped conduit


146


in the valve stem


144


does not communicate with the metering chamber


143


but rather only to the outside of the container


138


, and in particular with the space


167


defined between the inner circumferential surface of the head seal


131


and the lateral wall of the valve stem


144


and the chamber


116


in communication therewith. By providing the valve stem


144


in this intermediate position, propellant under pressure containing pharmaceutical substance present in the metering chamber


143


cannot escape therefrom and therefore only the propellant containing pharmaceutical substance present in the L-shaped conduit


146


in the valve stem


144


and the passageway


20


in the main body


4


need be exhausted. The provision of a sealing jacket of overpressure fluid about the part of the valve stem


144


which includes the inlet opening


148


following the filling operation and during the exhaust operation further advantageously provides that, when the container


138


is ultimately removed from the filling head


2


(in the final step following the step as illustrated in FIG.


13


), no residual propellant containing pharmaceutical substance can escape from the L-shaped conduit


146


in the valve stem


144


or the passage way


20


in the main body


4


prior to exhaustion thereof through the exhaust actuator


10


.




In a sixth step, as illustrated in

FIG. 12

, the exhaust valve assembly


48


is opened by retraction of the valve sealing end


51


of the exhaust valve stem


50


from the exhaust valve seat


67


. In this way, a communication path is provided between the L-shaped conduit


146


in the valve stem


144


, the passageway


20


in the main body


4


and the chamber


70


in the exhaust actuator


10


. The release of pressure from the propellant containing pharmaceutical substance on opening of the exhaust valve assembly


48


causes the propellant to boil off as a gas and escape through the passageway


73


in the valve block


44


into the chamber


70


. In this way, both the propellant and the pharmaceutical substance contained therein escape from the L-shaped conduit


146


in the valve stem


144


and the passageway


20


in the main body


4


into the chamber


70


. The provision of exhaust gas flows through the first, second and third exhaust gas inlet passages


84


,


92


,


93


create parallel flows to the gas escaping from the passageway


73


in the valve block


44


. This configuration creates substantially aligned flows between on the one hand the now gaseous propellant entraining pharmaceutical substance escaping from the passageway


73


in the valve block


44


and on the other hand the exhaust gas flows through the first, second and third exhaust gas inlet passages


84


,


92


,


93


downstream thereof. This configuration provides a uniform flow of gas in the chamber


70


which entrains the propellant and the pharmaceutical substance that escapes from the passageway


20


in the main body


4


and the L-shaped conduit


146


in the valve stem


144


. Preferably, the mass flow rate of the exhaust gas is at least 10 times the peak mass flow rate of the gaseous propellant flowing into the chamber


70


when the propellant boils off. In a preferred embodiment a vacuum pump incorporating a filter is connected to the exhaust tube


71


so as to collect the escaping pharmaceutical substance.




In a seventh step, as illustrated in

FIG. 13

, the exhaust valve assembly


48


is closed by urging the valve sealing end


51


of the exhaust valve stem


50


against the exhaust valve seat


67


, the fluid supplied to the conduit


126


in the slide body


16


to provide a sealing jacket around the part of the valve stem


144


which includes the inlet opening


148


is terminated and the exhaust gas supplied to the first, second and third exhaust gas inlet passages


84


,


92


,


93


is terminated. The actuator mandrel


14


is raised, thereby to raise again the filling head


2


relative to the container


138


so that the slide body


16


is spaced by the normal gap from the main body


4


. In this way, the valve stem


144


is raised from the intermediate position to the extended position, thereby to provide the metering chamber


143


of the container


138


in communication via the U-shaped conduit


151


in the valve stem


144


with the storage chamber


140


of the container


138


.




In a final step the container


138


is removed from the filling head


2


without inadvertent leakage of propellant and pharmaceutical substance to the atmosphere. The filling head


2


is then ready for the next filling cycle for a subsequent container.




Finally, it will be understood by a person skilled in the art that the present invention has been described in its preferred embodiment and can be modified in many different ways without departing from the scope of the invention as defined in the appended claims.



Claims
  • 1. A filling apparatus for introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propellant under pressure, comprising:a main body including a passageway for communicating, in use, with a valve stem extending from a head of a body of a container, the container comprising a metering chamber selectively communicatable by the valve stem with the atmosphere and a storage chamber defined by the body; a fill actuator comprising a filling valve assembly in communication with the passageway for selectively introducing thereinto propellant under pressure containing a substance in a suspension or solution; an exhaust actuator comprising an exhaust valve assembly in communication with the passageway for selectively exhausting therefrom propellant under pressure containing substance; and a container-engaging body in communication with the passageway for receiving, in use, the head of the body of the container, the container-engaging body being movable relative to the main body so as thereby to cause the valve stem of the container to be selectively positioned in an extended closed position, a depressed open position or an intermediate position therebetween, in which intermediate position the metering chamber of the container is closed to the atmosphere said container engaging body including an annular seal disposed about a lower end of the chamber against which, in use, is abutted against the head of the body of the container which surrounds the valve stem thereof.
  • 2. The filling apparatus according to claim 1, further comprising biasing means for biasing the container-engaging body away from the main body.
  • 3. The filling apparatus according to claim 2, wherein the biasing means comprises at least one compression spring disposed between the main body and the container-engaging body.
  • 4. The filling apparatus according to claim 1, wherein the main body includes an outwardly-extending part through which the passageway extends and which is sealingly received within a bore in the container-engaging body.
  • 5. The filling apparatus according to claim 4, further comprising an annular seal disposed at the distal end of the outwardly-extending part of the main body, which seal is, in use, abutted by the distal end of the valve stem of the container.
  • 6. The filling apparatus according to claim 1, wherein the container-engaging body includes a chamber of greater radial dimension than the valve stem of the container into which, in use, extends the valve stem of the container and a conduit in communication with the chamber for feeding a pressurised fluid thereto.
  • 7. The filling apparatus according to claim 1, wherein the annular seal comprises an O-ring.
  • 8. The filling apparatus according to claim 1, wherein opposing surfaces of the main body and the container-engaging body include one or the other of at least one projection and at least one recess , whereby, when the main body and the container-engaging body are moved together, the at least one projection is engaged within the at least one recess.
  • 9. A filling system for introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propellant under pressure incorporating the filling apparatus according to claim 1.
  • 10. A method of introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propellant under pressure, comprising the steps of:providing a container comprising a body defining a storage chamber , a valve stem extending from a head of the body and a metering chamber selectively communicatable by the valve stem with the atmosphere and the storage chamber , the valve stem having an outlet opening and a lateral inlet opening and being movable between an extended closed position in which the lateral inlet opening is located outside the body and a depressed open position in which the lateral inlet opening is located within the body; sealing the head of the body of the container which surrounds the valve stem thereof from ambient atmosphere; communicating the outlet opening of the valve stem of the container with a passageway in a main body of a filling apparatus ,the filling apparatus comprising a fill actuator comprising a filling valve assembly for selectively introducing into the passageway propellant under pressure containing a substance, in particular a pharmaceutical substance, in a suspension or solution and an exhaust actuator comprising an exhaust valve assembly for selectively exhausting from the passageway propellant under pressure containing substance; depressing the valve stem of the container so as to provide a communication path to the storage chamber thereof; opening the filling valve assembly thereby to fill the storage chamber of the container with propellant under pressure containing a substance, in particular a pharmaceutical substance, in a suspension or solution; closing the filling valve assembly; moving the valve stem of the container to an intermediate position between the depressed open position and the extended closed position, in which intermediate position the metering chamber of the container is closed to the atmosphere and the lateral inlet opening in the valve stem of the container is located outside the body thereof; and opening the exhaust valve assembly to enable propellant under pressure containing substance in the passageway and the valve stem of the container to exhaust.
  • 11. The method according to claim 10, wherein the filling apparatus further comprises a container-engaging body which is movably disposed to the main body thereof and is adapted to receive the head of the body of the container which includes the valve stem thereof, and further comprising the step of biasing the container-engaging body away from the main body of the filling apparatus.
  • 12. The method according to claim 11, wherein the main body of the filling apparatus includes an outwardly-extending part through which the passageway extends and which is sealingly received within a bore in the container-engaging body.
  • 13. The method according to claim 12, further comprising the step of sealing the distal end of the outwardly-extending part of the main body against the distal end of the valve stem of the container.
  • 14. The method according to claim 10, further comprising the step of surrounding the part of the valve stem of the container which includes the lateral inlet opening and extends from the body of the container with a pressurised fluid at least when the exhaust valve assembly is opened to exhaust propellant under pressure containing substance from the passageway and the valve stem of the container.
  • 15. The method according to claim 14, wherein the pressurised fluid is at a pressure greater than the vapour pressure of the propellant under pressure containing substance.
  • 16. The method according to claim 14, wherein the fluid is a gas.
  • 17. The method according to claim 16, wherein the gas is one of air or nitrogen.
Priority Claims (2)
Number Date Country Kind
9801398-0 Apr 1998 SE
PCT/SE99/00650 Apr 1999 SE
Parent Case Info

This application is a continuation of application Ser. No. 09/819,859, filed Mar. 29, 2001, now abandoned, the entire content of which is hereby incorporated by reference in this application.

US Referenced Citations (12)
Number Name Date Kind
2505799 Smith May 1950 A
2947904 Focht Aug 1960 A
2958170 Mayer, Jr. Nov 1960 A
2963834 Stanley et al. Dec 1960 A
3186451 Stanley Jun 1965 A
3745741 Cunningham et al. Jul 1973 A
3755985 Rait et al. Sep 1973 A
3995666 Michaels Dec 1976 A
4917156 Varlet Apr 1990 A
4999976 Smith Mar 1991 A
5345980 Burt et al. Sep 1994 A
6691746 Brennan et al. Feb 2004 B2
Foreign Referenced Citations (4)
Number Date Country
0056701 Jul 1982 EP
0 419 261 Mar 1991 EP
633 190 Jan 1995 EP
119265 Apr 1970 NO
Continuations (1)
Number Date Country
Parent 09/819859 Mar 2001 US
Child 10/406241 US