MXPA00010189A - Method, apparatus and system for filling containers - Google Patents

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

METHOD, APPARATUS AND SYSTEM FOR FILLING CONTAINERS DESCRIPTION OF THE INVENTION The present invention relates to an apparatus for filling, a system for filling, and a method for introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propeller under pressure. More 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 carried in and out of the communication with the containers that are going to be filled. The containers for retaining a suspension or solution of a pharmaceutical substance in a propellant under pressure are well known. One such container comprises a body defining a storage chamber, a valve rod extending from a body head and a measuring chamber that is selectively communicable by the valve rod with the atmosphere and the storage chamber; the valve stem provides, by means of an L-shaped conduit extending between the free end and the wall thereof, the outlet of the container through which the metered doses of the propellant containing the pharmaceutical substance are supplied. The valve rod is axially displaceable between a first extended position in which the measuring chamber, and therefore the container, is closed to the atmosphere, since the L-shaped conduit is completely placed outside the measuring chamber and a second sunken position, in which the measuring chamber is in communication with the outlet provided by the L-shaped conduit in the valve stem and through which a metered dose of the propellant containing the pharmaceutical substance is supplied. The container is filled with the valve stem in the sunken position, with the propellant containing the pharmaceutical substance being forced down through the L-shaped conduit in the valve stem through the measuring chamber and into the 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, whose filling system includes a filling apparatus which prevents the escape of the pharmaceutical substance towards the atmosphere. In this filling system. The filling apparatus is configured to be flushed with a volume of high pressure propellant, while still in fluid communication with the container so that the propellant under pressure containing the pharmaceutical substance remaining in the filling apparatus after the filling the container with it is washed through the container before the removal of the filling apparatus from the container. This configuration, however, requires an additional propellant to be introduced into the container to achieve washing. In addition, from the washing action, the propellant under pressure present in the valve stem can escape into the atmosphere. The present invention in at least one preferred aspect aims to provide an improved filling apparatus the which at least partially overcomes the problems before • mentioned. The present invention also aims to provide a filling method and system that are configured to fill a container without requiring the release of the propellant. alone or the propellant containing the pharmaceutical substance directly into 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 propeller under pressure comprising: a main body including a passage for communication, in use, with a valve stem extending from a head of a body of a container, the container comprising a selectively communicable measuring chamber. through a valve stem with atmosphere and a storage chamber defined by the body; a filling actuator comprising a filling valve assembly in communication with the passage to selectively enter • the same the propellant under pressure that contains a substance 5 in a suspension or solution; an exhaust actuator comprising an exhaust valve assembly in communication with the passage to selectively release from it the propellant under pressure that contains the substance; a body that couples the container in communication with the passage to receive, in use, the container body head, the • body that engages the container that is movable relative to the main body to thereby cause the valve stem of the container to be selectively placed in an extended closed position, an open position sunken or an intermediate position between both, in which intermediate position the measuring chamber of the container is closed to the atmosphere. Preferably, the filling apparatus comprises • also deviating means to deflect the body that engages the container away from the main body. More preferably, the diverting means comprise at least one compression spring positioned between the main body and the body that couples the container. Preferably, the main body includes an outwardly extending portion through which the passage extends and which is received in a sealed manner within a hole in the body that engages the container. More preferably, the apparatus further comprises an annular seal positioned at the distal end of the outwardly extending portion of the main body, which seal is, in use, spliced by the distal end of the valve stem of the container. Preferably, the body that engages the container includes a chamber of greater radial dimension than the valve stem of the container within which, in use, the valve stem of the container and a conduit in communication with the chamber for fluid delivery are extended. pressurized in it. Preferably, the body that engages the container includes an annular seal placed around a lower end of the chamber against which, in use, the head of the container, which surrounds the valve stem thereof, is spliced. More preferably, the annular seal comprises a ring in the form of 0. Preferably, the opposing surfaces of the main body and the body that engages the container include one or the other of at least one projection and at least one recess, for which, when the main body and the body that engages the container move together, at least one projection is engaged within 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 filling apparatus described above. The present invention further provides a method of introducing into a vessel a suspension or solution of a substance, in particular a pharmaceutical substance, • in a propeller under pressure, comprising the steps of: providing a container comprising a body defining a storage chamber, a valve stem extending from a body head and a measuring chamber selectively communicable by the valve rod with the atmosphere and the storage chamber, the valve rod having an outlet opening and an inlet opening and which is movable between an extended closed position. • in which the entrance opening is located outside the body and a sunken open position in which the entry opening is located inside the body; communicating the outlet opening of the valve stem of the container with a passage in a main body of the filling apparatus, the filling apparatus comprises a filling actuator that comprises a filling valve assembly for selectively introducing into the passage the 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 evacuating from the passage to the propellant under pressure that contains the substance; pressing the valve stem of the container to provide a communication path to the storage chamber thereof; opening the filling valve assembly thereof to fill the storage chamber of the pressure-propellant container containing a substance, in particular a pharmaceutical substance, in a suspension or solution; close the filling valve assembly; moving the valve stem of the container to an intermediate position between the sunken open position and the extended closed position, in which intermediate position the container measuring chamber is closed towards the atmosphere and the inlet opening in the valve stem of the container is located outside the body of the same; and opening the exhaust valve assembly to allow the propellant under pressure containing the substance in the passage and the valve stem of the container to have an outlet. Preferably, the filling apparatus further comprises a body that couples the container that is movably positioned to the main body thereof and is configured to receive the head of the body of the container including the valve stem, and the method further comprising the step of diverting the body that couples the container away from the main body of the filling apparatus. More preferably, the main body of the filling apparatus includes an outwardly extending portion through which the passage extends and which is received in a sealed manner within a hole in the body that couples the container. More preferably still, the method comprising the step of sealing the distal end of the part extending outward from the main body against the distal end of the valve stem of the container. Preferably, the method further comprises the step of encircling the valve stem portion of the container including the inlet opening and extending from the container body with a pressurized fluid at least when the exhaust valve assembly is opened to give exit to the propeller under pressure that contains the substance from the passage and the valve stem of the container. Preferably, the pressurized fluid is at a pressure greater than the vapor pressure of the propellant under the pressure that contains the substance. . In a preferred embodiment the fluid is a gas.

Preferably, the gas is air or nitrogen. BRIEF DESCRIPTION OF THE DRAWINGS A preferred embodiment of the present invention will now be described by way of example only with reference to the accompanying drawings in which: Figure 1 illustrates a partial side sectional view of a filling head in accordance with a preferred embodiment of the present invention; Figure 2 illustrates a vertical sectional view (along section A-A) of the filling head of Figure 1; Figure 3 illustrates a horizontal sectional view (along section B-B) of the filling head of Figure 1; Figure 4 illustrates a bottom plan view of the filling head of Figure 1; Figure 5 illustrates an end view of the filling head of Figure 1, illustrated with part of the exhaust actuator housing removed; Figure 6 illustrates a schematic representation of a filling system according to a preferred embodiment of the present invention for introducing into a container a suspension or solution of a pharmaceutical substance in a propeller under pressure, with the system incorporating the filling head of Figure 1; and Figures 7 to 13 illustrate side views in elongated partial section of the filling head portion of Figure 1 in a series of respective positions representing successive sequential steps in an operation of filling of container. Figures 1 to 5 illustrate a filling head 2 according to a preferred embodiment of the present invention. The filling head 2 comprises a body main 4 which includes a part that extends downwards • 5, extending from a bottom surface 6 thereof, a filling actuator 7 placed towards a side part of the main body 4 and an exhaust actuator 10 placed towards the opposite side of the main body 4.

The filling head 2 further comprises a driving mandrel 14 positioned towards and on the main body 4 by means of which the filling head 2 moves vertically. The filling head 2 comprises even a • sliding body 16 to receive a container that is going to filling that is mounted to the downwardly extending part 5 of the main body 4 to be movable vertically relative thereto. The main body 4 includes a vertically oriented passage 20 which is located substantially in is a central shape 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 and 22, respectively, communicate with the filling actuator 7 and the exhaust actuator 10. The filling actuator 7 comprises a housing 28 and a filling valve assembly 29, which is movably placed on the same. The fill valve assembly 29 comprises a fill valve rod 30 which is slidably disposed within an annular chamber 31 in the main body 4 and includes a valve seal end 32 which seals against a valve seat 33 which defines the first opening 21 of the passageway 20 in the main body 4. The chamber 31 includes an inlet duct 34 and an outlet duct 35 formed in the main body 4 in opposite side portions of the chamber 31. The filling valve assembly 29 further comprises a reciprocatingly movable filling valve member 36 which is axially coupled to the filling valve rod 30 and is sealingly positioned within the annular chamber 37 defined in the housing 28. The filling valve member 36 includes a part radially extending outwardly dividing the chamber 37 in sealed manner in first and second chamber parts 39, 40, the first chamber part 39 which it is close to the filling valve stem 30 and the second chamber part 40 which is remote from the filling valve rod 30. The housing 28 includes a conduit 41 communicating with the second chamber part 40 of the chamber 37 and is for connection to a source of pressurized fluid. The filling valve assembly 29 still comprises deviating means 42 in this mode a compression spring, for deflecting the filling valve member 36 and thus the filling valve rod 30 in the chamber 31 in the main body 4. The application / removal of the pressurized fluid by means of the conduit 41 introduces / removes the fluid from the second part of the chamber 40 of the chamber 37, thereby causing the sliding movement of the filling valve member 36 in the chamber 37, and therefore the sliding movement of the filling valve rod 30 in the chamber 31. In this manner, the valve sealing end 32 of the filling valve rod 30 can move in and out of engagement with the valve seat 33 which communicates with the first opening 21 of the passage 20 in the main body 4. The chamber 31 is sealed at the end thereof remote from the valve tape 33 and at the union of the valve member of the valve body 33. filling 36 and the filling valve stem 30 by a flexible annular seal 43 surrounding the filling valve stem 30.

The exhaust actuator 10 comprises a valve block 44 which is placed 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 positioned 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 seated in a sealed manner in the support sleeve 49. The exhaust valve stem 50 is generally conical in shape, and increases in diameter away from the end valve sealer 51. In this embodiment, the exhaust valve stem 50 includes a peripheral rim 52, which acts to reduce the retention of the substance therein. The exhaust valve assembly 48 further comprises an escape valve member of reciprocatingly moving movement 54 that is axially coupled to the exhaust valve stem 50 and is sealingly positioned within an annular chamber 56 in the support sleeve 49. The exhaust valve member 54 includes a radially outwardly extending central portion 58 that septably divides the chamber 56 into the first and second chamber portions 60, 62, the first chamber portion 60 that is close to the piston rod. exhaust valve 50 and the second chamber part 62 which is remote from the exhaust valve stem 50. The support sleeve 49 includes first and second conduits 64, 66 for connection to a source of pressurized fluid, each conduit 64, 66 which communicates with a respective one of the first and second chamber parts 60, 62 of the chamber 56. The application of fluid pressure by means of one of the conduits 64, 66 introduces fluid d into a respective one of the first and second chamber parts 60, 62 of the chamber 56, thereby causing the slidable movement of the exhaust valve member 54 in the chamber 56, and therefore the sliding movement of the valve rod. exhaust 50 in the support sleeve 49. In this form, the valve sealing end 51 of the exhaust valve stem 50 can move in and out of engagement with the 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 which also It is generally conical. The housing 46 further comprises an exhaust pipe 71 which is positioned on one 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 in the bottom of which is the exhaust valve seat 67. The valve block 44 further includes a fluid passage 73 therein that includes a first inlet opening 74. • communicating with the second opening 22 of the passage 20 in the main body 4 and a second exit opening 75 in the exhaust valve seat 67. In order to provide the required assembly for the support sleeve 49, the camera 70 in housing 46 is divided into three chamber parts arched 78, 80, 82 in the vicinity of assembly assembly • of exhaust valve 48 (as illustrated in Figure 5). In this embodiment, the three arched chamber parts 78, 80, 82 are substantially equal in circular length. The camera 70 is configured mainly for is evacuated 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 that encircle the outlet opening 75 in the valve seat. Exhaust valve 67. The first passages of exhaust gas inlet 84 includes respective outlets 86 that define an arrangement, preferably a circular arrangement, around the exhaust valve seat 67, with the arrangement being axially centered on a common shaft of the exhaust valve stem 50, the seat of exhaust valve 67 and passage 73. At least those portions of the first exhaust gas inlet passages 84 that define the outlets 86 are in parallel to passage 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 passage 73. The valve block 44 further includes an annular chamber 88 on an external surface thereof that commonly connects the first exhaust gas inlet passages 84, and which is in communication with a duct 90 in the main body 4 to supply a source of an exhaust gas thereto. In this embodiment, the duct 90 is directed radially towards the annular chamber 88, although in an alternative embodiment it could be directed tangentially. The chamber 70 is further configured to be evacuated with an exhaust gas passing through the housing 46. In this embodiment, the housing 46 includes a plurality of seconds and third exhaust gas inlet passages 92, 93 downstream of the first passages. exhaust gas inlet 84. The second and third exhaust gas inlet passages 92, 93 include respective outlets 94, 95, which define an arrangement, preferably a circular arrangement, around the seat of the exhaust valve 67 and communicate with the chamber 70. At least those portions of the second and third exhaust gas inlet passages 92, 93 that include the outlets 94, 95 are parallel to the first exhaust gas inlet passages 84, and therefore also parallel to passage 73 in the valve block 44. The housing 46 includes an annular chamber 96 that commonly connects the second and third exhaust gas inlet passages 92, 93 and a conduit 98 in communication with the chamber 96 to supply a source of an exhaust gas to it. The sliding body 16 is mounted for the vertical sliding movement in relation to the body • main 4 by the first and second separated diverter elements 100, in this embodiment, compression springs placed between them. Each of the diverter elements 100 is mounted on a member respective threaded 102, both threaded members 102 connecting the sliding body 16 to the main body 4. In the normal or non-operative configuration, the sliding body 16 is deflected by the diverting elements 100. • downward away from main body 4 to be separated therefrom by a space 103. The sliding body 16 includes a hole 104 for slidably receiving in mating relation the downwardly extending portion 5 of the main body 4. The sliding body 16 further includes a projection 105 in the upper surface 106 thereof which is complementary to the corresponding recess 107 formed in the lower surface 6 of the main body 4 around the downwardly extending part 5. The hole 104 includes an annular seal 109 surrounding the extending part down to form a fluid tight seal therebetween. The lower distal end 110 of the downwardly extending portion 5 is provided below with an annular valve stem seal 112 which includes a central opening 113 which is aligned with the passage 20 in the main body 4, the internal diameters and external of the valve stem seal 112 corresponding substantially with respect to the internal diameter of the third opening 25 in the passage 20 and the internal diameter of the hole 104. The hole 104 defines a chamber 116 that is configured to have an internal diameter that is greater than the external diameter of the valve stem of the container to be filled. The chamber 116 includes a main upper section 122 and a lower section 123 that is slightly smaller in diameter than the upper section 122 and defines an opening 124 through which the valve stem of the container to be filled extends. The sliding body 16 further includes a conduit 126 which is in communication with the chamber 116. The sliding body 16 further comprises an annular head seal 131 which is located below and surrounds the opening 124 of the chamber 116. The head seal 131 is retained in a central opening 133 in a retaining block 132 that provides the lower part of the sliding body 16. The seal retaining block -132 includes a downwardly extending recess 134 in a lower surface 135 thereof to receive the head of a container that is going to be filled. As illustrated in Figure 7, in this embodiment, a container 138 is to be filled by the filling head 2 comprising a body 139 defining a storage chamber 140 for retaining a suspension or solution of a pharmaceutical substance in a propellant. under pressure. The body 139 includes a head 141 that includes a peripheral housing 142 defining a measuring chamber 143 and a valve stem 144 that is movably positioned in the housing 142 and extends from the head 141. The valve stem 144 is movable between an extended position (as illustrated in Figure 7) and a sunken position (as illustrated in Figure 8), valve stem 144 which is normally biased by a compression spring 145 in the extended position. The valve stem 144 includes an L-shaped conduit 146 extending between a first outlet opening 147 located at a distal end of the valve stem 144 and a second inlet opening 148 located in the side wall of the valve stem 144. The valve stem 144 further includes a U-shaped conduit 151 in that portion thereof which is always located within the container 138. The U-shaped conduit 151 includes the first and second conduits. • axially positioned openings 153, 155 located in the side wall 5 of the valve stem 144 and allows communication between the measuring chamber 143 and the storage chamber 140 of the container 138 by means of holes 156 in the housing 142. When the rod of valve 144 is in the extended position (as illustrated in Figure 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 measuring chamber 143 inside the container 138. Therefore, when the valve rod 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 duct 146 in the valve stem .144. In the extended position, the U-shaped conduit 151 communicates by means of the first opening 153 and the holes 156 in the housing 142 with the storage chamber 140 and by means of the second opening 155 with the measuring chamber 143. In this position, with the container 138 inverted, the measuring chamber 143 is filled. 25. When the valve stem 144 is in the depressed position (as illustrated in Figure 8), ie one of a filling position or a discharge position, the valve rod 144 is pushed against the action. • diverter of the diverter element 145, whereby it moves the inlet opening 148 of the L-shaped duct 146 in communication with the measuring chamber 143 and the U-shaped duct 151 out of communication with the measuring chamber 143 and only in communication with the storage chamber 140 by means of the holes 156 in the housing 142. In a filling operation, a solution or • suspension of a pharmaceutical substance in a propellant under pressure is forced down through an L-shaped conduit 146, through the measuring chamber 143 and into the storage chamber 140 of the container 138 which is forced to pass an annular seal 166 surrounding the valve stem 144 at the bottom of the measuring chamber 143. During the discharge of a measured volume of a suspension or solution of a pharmaceutical substance in a • pressure vessel propeller 138, the volume measured of the suspension or solution present in the measuring chamber 143 is allowed to flow out through an L-shaped duct 146 by providing a communication path between the measuring chamber 143 and the inlet opening 148 of the duct in the form of L 146. In the operation of discharge, the seal 166 prevents any suspension or solution in the storage chamber 140 from entering the measuring chamber 143 so that a precise volume is discharged. In this modality, the structural components • Main filler heads 2 are typically 5 stainless steel compounds and the seals are commonly composed of nitrile rubber. The only exceptions are the diaphragm seals and the seals that come in contact with the propellant that are typically composed of PTFE and the valve block 44 and the exhaust valve stem 50 that are typically composed of hardened stainless steel.

• Figure 6 illustrates a filling system incorporating the filling head described above 2 for filling a container 138 with a measured volume of a suspension or solution of a pharmaceutical substance in a low propellant. pressure. The filling head 2 is included in a circulation line, generally designated by the reference numeral 170, in which a propellant under pressure containing a pharmaceutical substance in a suspension or The solution is circulated. The circulation line 170 includes a mixing container 172 that holds the propellant containing the pharmaceutical substance in a suspension or solution. The mixing vessel 172 is pressurized as in the remainder of the circulation line 170, so that the propellant is not only under pressure, but also maintained as a liquid where the boiling point of the propellant is lower than that of the ambient temperature. A line 176 connects an outlet 174 of the container • of mixing 172 to a pump 178, whose pump 178 is provided for pumping the propeller around the circulation line 170. Another line 180 connects the pump 178 to the inlet side of an inlet valve 182. An additional 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 measured volume of the propellant that • contains the pharmaceutical substance in a suspension or solution in an opening of the inlet valve 182. The volume measured corresponds to the volume that is required to be introduced into the container 138 by the head of filling 2. Still an additional line 186 connects the measuring chamber 184 to the filling head 2, specifically the inlet duct 34 in the main body 4 of the filling head 2. As described above, the inlet duct 34 communicates with camera 31 surrounding the filling valve rod 30 and from there with the outlet conduit 35. An additional line 188 connects the filling head 2, specifically the outlet conduit 35 in the main body 4 of the filling head 2, input side of an outlet valve 190. A line additional 192 connects the outlet side of the outlet valve 190 to an inlet 194 of the mixing container 172, thereby completing the circulation 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 measured volume of a suspension or solution of a pharmaceutical substance in a propellant under pressure and the consequent exit of the resulting propellant under pressure containing the pharmaceutical substance will be described below with reference to Figures 6 to 13. In a first step, as illustrated in Figure 7, the The head 141 of a container 138 to be filled is located within the downwardly extending recess 134 in the seal retention block 132 of the sliding body 16. In this position, the head 141 of the container 138 abuts against the head seal 131 and the distal end of the valve stem 144 of the container 138 abuts against the valve stem seal 112, inside the valve stem 144 which is driven in the position extended by the diverter element 145. In this way, the chamber 116 is sealed by the valve stem and the head seals 112, 131. Although not illustrated, it will be understood that the bottom of the container 138 is supported and urged upwards. Further, in this position, the diverter elements 100 urge the sliding body 16 away from the main body 4 to provide space 103 therebetween, and the fill valve assembly 29 and the exhaust valve assembly 4'8 are closed. In a second step, as illustrated in Figure 8, the driving mandrel 14 is operated to move the main body 4 and the filling actuator 7 and the exhaust actuator 10 placed therein downward relative to the sliding body 16. against the deflection of the diverter elements 100. This movement causes the projection 105 to pass into the recess 107 and the space 103 to be closed. Additionally, the downwardly extending portion 5 of the main body 4 is driven by the valve stem seal 112 against the distal end of the valve stem 144 of the container 138, thereby pushing 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 measuring chamber 143 of the container 138 and the U-shaped conduit 151 in the valve stem 144 is located only in communication with the storage chamber 140 of the container 138 and out of communication with the measurement chamber 143.

In a third step, as illustrated in Figure 9, the fill valve assembly 29 is opened by retracting the valve 32 sealant end of the rod. • of filling valve 30 from the valve seat 33. A measured volume of the propellant containing the pharmaceutical substance in suspension or solution present in the measuring chamber 184 is then introduced through the inlet conduit 34, through the annular chamber 31, through passage 20, through the L-shaped conduit 146 in the valve stem 144, through the measuring chamber 143 • of the container 138 and finally passes the seal 166 into the storage chamber 140 of the container 138 by means of the holes 156 in the housing 142. Before opening the filling valve assembly 29, the inlet valve 182 and the outlet valve 190 in the circulation 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 measuring chamber 184, the measuring chamber 184, the line 186 which connects the measuring 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 filled with a propellant containing the pharmaceutical substance in suspension or solution. When the measuring chamber 184 is emptied to a The volume of propellant under pressure containing the pharmaceutical substance corresponding to that measured by the measuring chamber 184 is passed through the line 186 and into the filling head 2 through the inlet duct 34. In this way, a precisely measured volume of the propellant containing the pharmaceutical substance in suspension or solution is introduced into the container 138. In order that the pump 178 can continue to operate continuously, the circulation of the propellant containing the pharmaceutical substance around the circulation line 170, when the inlet valve 182 • and the outlet valve 190 are closed, the bypass valve 196 is opened. In a fourth stage, as illustrated in Figure 10, after a measured volume of propellant that contains the pharmaceutical substance in suspension or solution has been introduced into the container 138, the filling valve assembly 29 is closed by deviation of the valve sealing end 32 of the valve stem from • filling 30 against the valve seat 33. Therefore, two separate operations are started in order to eliminate the inadvertent release of the propellant containing the 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 sliding 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 side wall of the valve stem. • 144 of the container 138. This fluid is supplied at a higher pressure than the vapor pressure of the propellant under pressure which contains the 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 air or nitrogen. • In a second operation, an exhaust gas, preferably air or nitrogen, is introduced under pressure into the chamber 70 in the exhaust actuator 10 by means of the first, second and third gas inlet passages. exhaust 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 propellant containing the substance • Pharmaceutical that comes out through chamber 70 is again liquefied in it. Typically, when air is used as the exhaust gas, the mass flow rate is in the range of 0.1 to 10 grams / second, preferably about 2 grams / second. In a fifth stage, as illustrated in Figure 11, the actuator mandrel 14 is partially raised thereby partially releasing the valve stem 144 from the container 138 to an intermediate position between the extended closed position (as illustrated in Figure 7) and # the sunken open position (as illustrated in Figure 8). In this intermediate position, the inlet opening 148 of the L-shaped duct 146 in the valve stem 144 of the container 138 is raised so as not to be in communication with the measuring chamber 143 of the container 138, although the space 167 defined between the circumferential surface internal of the head seal 131 and the side wall of the • valve stem 144 of container 138 and chamber 116 in communication therewith. The propellant under pressure containing the pharmaceutical substance that is present in the L-shaped conduit 146 in the valve stem 144 and the Passage 20 in the main body 4 does not escape therefrom by means of the inlet opening 148 in the valve stem 144 as a result of the excess pressure of the fluid supplied via the conduit 126. Therefore, after 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 seal jacket of a pressurized fluid around the part of the valve stem 144 that includes the L-shaped conduit 146 prevents the propellant under pressure containing the pharmaceutical substance which remains in the L-shaped duct 146 in the valve stem 144 and the passage 20 in the main body 4 escape through the inlet opening 148 in the valve stem 144, which propellant contains the pharmaceutical substance which another way would be released subsequently to the atmosphere after the removal of the container 138 from the filling head 2. When the valve stem 144 is in the intermediate position, the measurement chamber 143 of the container 138 closes to atmosphere, since the L-shaped conduit 146 in the valve stem 144 does not communicate with the measuring chamber 143 but only with 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 side wall of valve stem 144 and chamber 116 in communication therewith. By providing the valve stem 144 in this intermediate position, the pressurized propellant containing the pharmaceutical substance present in the measuring chamber 143 can not escape from it, and therefore only the propellant containing the pharmaceutical substance present in the L-shaped conduit 146 in the valve stem 144 and the passage 20 in the main body 4 need to be released. The provision of the fluid overpressure sealing jacket around the part of the valve stem 144 that includes the inlet opening 148 after the filling operation and during the exhaust operation advantageously also provides that when the container 138 is finally removed from the container. the filling head 2 (in the final stage following the step illustrated in Figure 13), there is no residual propellant containing pharmaceutical substance that can escape from the L-shaped duct 146 in the valve stem 144 or the passage 20 in the main body 4 before releasing it, before the exhaust actuator 10. In a sixth stage, as illustrated in Figure 12, the exhaust valve assembly 48 is opened by retracting the sealing end valve 51 of the exhaust valve stem 50 from the exhaust valve seat 67. In this form, a communication path between the conduit in the form of L 146 in the valve stem 144, the passage 20 in the main body 4 and the chamber 70 in the exhaust actuator 10. The pressure release from the propellant containing the pharmaceutical substance to the opening of the exhaust valve assembly 48 causes the propellant to evaporate as a gas and escapes through passage 73 in valve block 44 within chamber 70. In this form, the propellant and the pharmaceutical substance contained therein escape from the L-shaped conduit. 146 in the valve stem 144 and the passage 20 in the main body 4 within the chamber 70. The provision of the exhaust gas flows through the first, second and third exhaust gas inlet passages 84, 92, 93 create flows parallel to the gas leak from the passage 73 in the valve block 44. This configuration creates substantially aligned flows between on the one hand, the pharmaceutical substance to the gaseous propellant exiting from the passage 73 in the valve block 44 and on the other hand, to the exhaust gas flowing through the first, second and third exhaust gas inlet passages 84, 92, 93 downstream of it. This configuration provides a uniform flow of gas in the chamber 70 entering the propellant and the pharmaceutical substance exiting from the passage 20 in the main body 4 and the L-shaped conduit 146 in the valve stem 144. Preferably, the velocity 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 burns. In a preferred embodiment, a vacuum pump incorporating a filter is connected to the exhaust pipe 71 to collect the exiting pharmaceutical substance. In a seventh stage, as illustrated in the Figure 13, the exhaust valve assembly 48 is closed by driving 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 sleeve around the valve stem part 144 including the inlet opening 148 which is terminated and the exhaust gas supplied to the first, second and third passages • Exhaust gas inlet 84, 92, 93 that is finished. The actuator mandrel 14 is raised, thus raising again the filling head 2 relative to the container 138 so that the sliding body 16 is separated by the normal space from the main body 4. In this way, the piston rod valve 144 is raised from the position intermediate to the extended position, providing this • way the measuring chamber 143 of the container 138 in communication by means of 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 container. filling head 2 without inadvertent spillage of the propellant and the pharmaceutical substance into the atmosphere. The filling head 2 is then ready for the next • filling cycle of 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 various manners without departing from the scope of the invention as defined in the appended claims.

Claims (18)

1. CLAIMS 1. A filling device for introducing into a container a suspension or solution of a substance, in
2. • Particularly a pharmaceutical substance, in a propeller under 5 pressure, characterized in that it comprises: a main body including a passage for communication in use, with a valve stem extending from a head of a body of a container, the container which comprises a measuring chamber 10 selectively communicable via the valve rod with
3. • the atmosphere and a storage chamber defined by the body; a filling actuator comprising a filling valve assembly in communication with the passage for
4. Selectively introducing therein the propellant under pressure which contains a substance in a suspension or solution; an exhaust actuator comprising an exhaust valve assembly in communication with the passage to selectively output therefrom the propellant under pressure containing the substance; and a body that couples the container in communication with the passage to receive in use, the head of the body of the container, the body that engages the container, which is
5. Movable with respect to the main body to thereby cause the valve stem of the container to be selectively placed in an extended closed position, a sunken open position or an intermediate position therebetween, in the intermediate position, the measuring chamber of the container. vessel is closed towards the atmosphere. The filling apparatus according to claim 1, characterized in that it comprises diverting means for diverting the container coupling body away from the main body. The filling apparatus according to claim 2, characterized in that the diverting means comprise at least one compression spring placed between the main body and the body that couples the container. The filling apparatus according to any of claims 1 to 3, characterized in that the main body includes an outwardly extending portion through which the passage extends and which is received in a sealed manner within an orifice. in the body that connects the container. The filling apparatus according to claim 4, characterized in that it further comprises an annular seal placed at the distal end of the outwardly extending part of the main body, whose seal, in use, is spliced by the far end of the valve stem of the container. 6. The filling apparatus according to any of claims 1 to 5, characterized
6. • because the body that engages the container includes a chamber 5 of greater radial dimension than the valve stem of the container within which, in use, the valve stem of the container and a conduit in communication with the chamber for feeding of the container are extended. a pressurized fluid towards it. 10 7. The filling apparatus in accordance with
7. • claim 6, characterized in that the body that engages the container includes an annular seal placed around a lower end of the chamber against which in use the head of the container body surrounding the container is spliced.
8. 15 valve stem thereof. The filling apparatus according to claim 7, characterized in that the annular seal comprises an O-ring. 9. The filling apparatus according to any of claims 1 to 8, characterized in that the opposite surfaces of the The main body and the body that engages the container include one or the other of a projection and at least one recess, whereby, when the main body and the body that couples the container move together, at least one projection is coupled. within at least one recess. 10. A filling system to introduce a suspension or solution of a substance into a container, in particular, a pharmaceutical substance, in a pressurized propellant incorporating the filling apparatus according to any of claims 1 to 9. 11. A method of introducing into a container a suspension or solution of a substance, in particular , a pharmaceutical substance, in a propellant under pressure, characterized in that it comprises the steps of: providing a container comprising a body defining a storage chamber, a valve stem extending from a body head and a measuring chamber selectively communicable by the valve stem with the atmosphere and the storage chamber, the valve rod having an outlet opening and a side entry opening and which is movable between an extended closed position in which the lateral entry opening is located outside the body and an open sunken position in which the lateral entry opening is located inside of the body; communicating the inlet opening of the valve stem of the container with the passage in the main body of the filling apparatus, the filling apparatus comprising a filling actuator comprising a filling valve assembly for selectively introducing into the passage, the propellant under pressure that contains a substance, in particular a pharmaceutical substance, in a suspension or
9. • solution and an exhaust actuator comprising an exhaust valve assembly 5 for selectively outputting from the passage to the propellant under pressure containing a substance; pressing the valve stem of the container to provide a communication path for the storage chamber thereof; 10 opening the filling valve assembly whereby the storage chamber of the container is filled with the pressurized propellant containing a substance, in particular a pharmaceutical substance, in a suspension or solution; 15 close the fill valve assembly; moving the valve stem of the container to an intermediate position between the sunken open position and the extended closed position, in which intermediate position the container measuring chamber is closed to the atmosphere
10. 20 and the lateral inlet opening of the valve stem of the container is located outside the body thereof; and open the exhaust valve assembly to allow the propellant under pressure that contains the substance in the passage and the valve stem in the
11. 25 container have outlet.
12. 12. The method according to claim 11, characterized in that the filling apparatus further comprises a body that engages the container that is placed

    • movably towards the main body of the same, and is

    5 adapted to receive the head of the body of the container including the valve stem thereof and comprising the step of diverting the body that couples the container, away from the main body of the filling apparatus. The method according to claim 10 12, characterized in that the main body of the filling apparatus includes an outwardly extending portion through which the passage extends and which is received in a sealed manner within a hole in the body that connects the container. 15 14. The method according to the claim

    13, characterized in that it further comprises the step of sealing the distal end of the part extending outward from the main body against the distal end of the rod.

    # valve of the container. 15. The method according to any of claims 11 to 14, characterized in that it further comprises the step of encircling the valve stem portion of the container including the lateral entry opening and s.e extends from the container body with a fluid

    25 pressurized at least when the exhaust valve assembly is opened to release the propellant under pressure containing the substance from the passage and valve stem of the container. The method according to claim 15, characterized in that the pressurized fluid is at a pressure greater than the vapor pressure of the propellant under pressure that contains the substance. 17. The method according to claim 15 or 16, characterized in that the fluid is a gas. 18. The method according to claim 17, characterized in that the gas is air or nitrogen.

    SUMMARY An apparatus for filling, a system for filling and a method for introducing into a container a suspension or solution of a substance, in particular a pharmaceutical substance, in a propeller under pressure, the filling apparatus comprises: a main body (4) which includes a passage (20) for communicating when in use, with the valve stem (144) extending from a head (141) of a body (139) of a container (138); the container (138) comprises a measuring chamber that can be selectively communicated by the valve stem to the atmosphere, and a storage chamber (140) defined by the body (139); a filling actuator (7) comprising a filling valve assembly (29) in communication with the passage (20) for selectively introducing a propellant under pressure containing a substance into a suspension or solution; an exhaust actuator (10) comprising an exhaust valve assembly (48) in communication with the passage (20) to selectively discharge the propellant under pressure containing the substance, from the passage; and a body that is coupled to the container (16), in communication with the passage (20) to receive, in use, the head (141) of the body (139) of the container (138), the body that engages the container ( 16) includes a chamber (16), which can be moved relative to the main body (4) to thereby cause the stem of the valve (144) of the container (138) to be placed in a closed extended position, a open position or an intermediate position between them, in such intermediate position, the measuring chamber (143) of the container (138) is closed to the atmosphere.