WO2010124907A1

WO2010124907A1 - Method for checking the tightness of a container filled with a fluid

Info

Publication number: WO2010124907A1
Application number: PCT/EP2010/053667
Authority: WO
Inventors: Gerald Mathe; Christoph Hahn
Original assignee: Boehringer Ingelheim International Gmbh
Priority date: 2009-04-28
Filing date: 2010-03-22
Publication date: 2010-11-04
Also published as: EP2425224A1

Abstract

In a method for checking the tightness of a container (5) filled with a fluid (4), in which a fluid component exiting the container (4) is detected by using a sensor (8) responding to the fluid component, the container (5) is located in a closed chamber (3), in which the exiting fluid component is collected over a predetermined period of time, while a carrier gas flow is supplied to the sensor (8) by way of a bypass (12), and at the end of the period of time the carrier gas flow is conducted through the chamber (3) in order to supply the collected fluid component to the sensor (8). During the period of time in which the fluid component exiting the container (5) is collected in the chamber (3), a vacuum is applied to the chamber (3).

Description

Method for testing the tightness of a container filled with a fluid

description

The invention relates to a method for checking the tightness of a container filled with a fluid, in which a fluid component emerging from the container is detected by using a responsive to the fluid component sensor, wherein the container is in a closed chamber in which leaking fluid component is collected over a predetermined period of time during which a carrier gas stream is bypassed to the sensor and after expiration of the period the carrier gas stream is passed through the chamber to supply the collected fluid component to the sensor and a device, a container and an atomizer to.

In the field of leak testing of containers, it is customary to fill the interior of the sealed container with a trace gas, for example helium, in a much higher concentration than in normal air and to create a vacuum in a test chamber receiving the container to be tested. The test chamber is fluidly connected to a sensor for detecting the trace gas. Further DE 695 16 195 T2 describes a leak test method in which the pressure rise associated with the exit of the trace gas from the container is detected in the test chamber in order to assess the tightness of the container.

DE 103 16 332 B4 describes a method for checking the tightness of a container which is filled with a fluid, wherein a fluid component of the fluid received in the container, which emerges from the container without external negative pressure, is detected and used using a sensor which reacts on the fluid component determined value is compared with a specified limit. The container to be tested is arranged in a closed chamber and the fluid component emerging from the container is collected in the chamber for a predetermined period of time. At the end of the period, a carrier gas stream is passed through the chamber, which feeds the fluid collected in the closed chamber to the sensor. During the period in which the fluid component emerging from the container is collected in the chamber, the carrier gas flow is supplied to the sensor via a bypass.

It is an object of the invention to provide a method and an apparatus of the type mentioned, which is or used in series production with relatively low test times, wherein the device has a simple structure.

According to the invention, the object in the method is achieved in that during the period in which collected from the container fluid component in the chamber is, the chamber is subjected to a vacuum.

During the density test of the container, the carrier gas stream, preferably an air stream, is first led past the bypass chamber at the chamber to be tested, and a vacuum is created in the chamber, through which the gas bubble present in the container, in particular the air bubble, enters the container Closing the fluid-filled container is enclosed in the interior of the container, expands and at this expansion and an existing

Leakage in the container causes an increase in the concentration of the fluid component in the chamber. After the lapse of the time period during which the fluid leaving the container is collected under vacuum in the chamber, the flow of carrier gas through the chamber is directed to the sensor. Due to the applied pressure gradient, the mass transfer taking place in a leaking container can be detected much more quickly with the sensor than with permeation, which takes place only on the basis of a concentration drop. Due to the time advantage over prior art density tests, the inventive method is applicable in mass production for testing a relatively large number of containers. Of course, the sensor is adapted to the leaking from the container fluid component.

The vacuum is preferably maintained for a period of less than 60 s, in particular less than 40 s, preferably less than 30 s and particularly preferably less than 15 s. Accordingly, the process runs relatively quickly and is to be integrated into a manufacturing process. Currently- raum, in which the vacuum is maintained in the chamber, in particular of the material from which the container consists, the exiting fluid component and the desired accuracy of measurement dependent and easily determined by the skilled person.

To improve the measurement results, predetermined climatic conditions are set. Conveniently, the carrier gas stream is heated. With the temperature of the carrier gas flow is also a corresponding temperature control of the essential components of the device, in particular the flow-through pipes, valves and the chamber, accompanied. The temperature and humidity of the carrier gas flow are dependent, for example, on the sensor used. The carrier gas stream is passed, for example, at a temperature of 25 ° C through the device.

Preferably, the carrier gas stream is humidified or dehumidified. The carrier gas flow is adjusted to have a relative humidity of 75%.

The object is in the apparatus for checking the tightness of a container filled with a fluid comprising a sensor for detecting a leaking from the container fluid component, wherein the container is disposed in a closed chamber, which via a valve control with a gas line and a bypass for a carrier gas stream and connected to the sensor is inventively achieved in that the chamber is connected to a Va kuumpumpe. Accordingly, the device has a relatively simple structure. Of course, a controllable valve is provided between the chamber and the vacuum pump.

Preferably, the sensor is designed to detect ethanol vapor. The sensor is a semiconductor sensor which changes its resistance due to a change in the concentration of the ethanol vapor present in a leaky container in the wet carrier gas and thus allows a statement about a leakage rate.

In an embodiment, the sensor is coupled to an evaluation and display unit which stores measured values, compares them with limit values and outputs a visually and / or audibly perceptible signal when a limit value is exceeded. The limit is calculated to correspond to a loss of 0.1 mg of ethanol per day, as the fluid in the container is allowed to lose a maximum of 3% of this solvent by diffusion for a storage period of 3 years. Due to the signal, the container is either discharged from the production as a leaking rejects or further processed as a dense container. The operations of loading the chamber with containers and the discharge can be done both automatically and manually.

In order to remove as little gas within a short time from the chamber, the interior of the chamber is advantageously adapted to the size of the container.

The leakproof container, in particular for a nebulizer, for use in the method and / or in the chamber of the device is filled with an inhalable ethanolic drug formulation and designed according to any one of claims 11 to 14. However, the container can also be designed in accordance with the container for a nebulizer or inhaler known from WO 96/06011 A1, WO 00/49988 A2 and WO 99/43571 A1. Such a container has a rigid metallic outer shell and a bag received therein. The pouch forms a fluid space for drug delivery and collapses as the drug preparation is withdrawn.

It is understood that the features mentioned above and those yet to be explained below can be used not only in the combination indicated, but also in other combinations. The scope of the invention is defined only by the claims.

The invention will be explained in more detail below using an exemplary embodiment with reference to the accompanying drawings. It shows:

1 shows a schematic representation of a device according to the invention for carrying out the method according to the invention,

2 shows a sectional view of a container to be tested with the device,

3 shows a sectional view of an atomizer in the untensioned state with the container of Fig. 2 and

4 is a sectional view of the atomizer in the tensioned th state.

The device comprises a supply line 1 for a carrier gas formed as air, which passes with a specific relative humidity, a predetermined temperature and at a set speed via a first valve device 2 into a chamber 3 in which a container 5 filled with a fluid 5 is arranged is. In the chamber 3 protrudes a discharge line 6, the part with a second valve means 7 and a sensor 8 for detecting a leaking from the leaky container 5 Fluidbestand- part. The first valve device 2 is connected via a bypass 12 to the second valve device 7. In addition, a vacuum line 9 is inserted into the chamber 3, which communicates with a vacuum valve 11 with the interposition of a third valve device 10.

During the tightness test of the container 5, initially the carrier gas stream sucked from the environment flushes the chamber 3 and flows through the sensor 8 under approximately constant conditions. The chamber 3 is then decoupled from the carrier gas stream by the first valve device 2 and the second valve device 7 via the bypass 12 continues to flow through the sensor 8 and finally again, possibly cleaned, gets into the environment. By means of the vacuum pump 11, a negative pressure is generated in the chamber 3 through which the gas bubble present in the container 5, which is trapped in the interior of the container 5 when closing the container 4 filled with fluid 4, expands when the container 5 is leaking , Otherwise, the vacuum has no significant effect on the container 5. Does the gas bubble expand inside the leaky container 5 During the period of the vacuum, an increase in the concentration of the fluid constituent emerging from the container 5 takes place in the chamber 3. After the expiry of the adjustable period in which the fluid constituent exiting from the container 5 is collected under vacuum in the chamber 3 After a corresponding switching of the three valve devices 2, 7, 10, the carrier gas flow is conducted through the chamber 3 to the sensor 8, which detects the increased concentration of the fluid constituent in the carrier gas flow and supplies measured values to an evaluation unit which corresponds to a corresponding threshold value Signal outputs. If the container is tight, the concentration of the volatile fluid constituent in the carrier gas stream does not increase or substantially and the evaluation unit can not determine that the limit value has been exceeded.

The fluid 4 is an ethanol-containing drug formulation which is filled in the substantially cylindrical container 5 in an amount sufficient (typically 2 to 10 or 2 to 15 ml) to allow multiple doses or applications which is insertable into a nebulizer 13.

The container 5 has in its interior a bag-like or tube-like fluid space 14 for receiving the fluid 4. A wall 15 delimiting the fluid space 14 is at least partially flexible, deformable and / or collapsible.

The fluid space 4 or the wall 15 is in a first th connection 16 opposite end portion 17 closed by welding the wall 15. In addition, the container or its outer shell 18 in this end region 17 on a bottom piece 19 which closes the outer shell 18 the end face firmly and which is provided with a ventilation opening 20.

The at least substantially rigid outer sheath 18 preferably connects the connection 16 or a connection piece 21 fixing the connection piece 21 sufficiently rigidly with the bottom piece 19 in order to be able to insert the container 5 into the atomizer 13 by appropriate pressure on the bottom piece 19 and / or to be able to pull the container 5 out of the atomizer 13 by pulling on the bottom piece 19 again.

The film-like wall 15 in the container 5 is at least partially deformable, in order to allow a possible slight collapse of the fluid space 14 in the removal of fluid 4, since the fluid space 14 is largely sealed gas-tight. The wall 15 has a multilayer structure and has an outer layer, a preferably metallic barrier layer, in particular a metal foil, and an inner layer and optionally further layers. The individual layers can be formed, for example, by coating, laminating or in any other suitable manner. The barrier layer is designed in particular as an aluminum layer or foil.

The outer shell 18 is partially extruded onto the wall 15, that is, from the outside, and lies with its inside indirectly on the outside of the wall 15, as is the case in a contact area 22 indicated in FIG. 2. During production, a sleeve is first formed from the film material forming the wall 15 by longitudinal welding of a corresponding material strip. Then the outer shell 18 is extruded as an endless tube.

The wall 15 is at least partially or in total detachable from the outer shell 18, since the outer shell 18 is not fixed to the wall 15 connects. The outer shell 18 is made of a first material, which does not bind to the outer layer of the wall 15 or a second material which forms the outer layer of the wall 15. The two materials are therefore preferably different, but also adhesion preventers can be used.

The first material is preferably a PE (polyethylene) or a PET (polyethylene terephthalate). When PE is selected for the first material, preferably PET or another material not joining with PE is selected for the second material. If PET is selected for the first material, it is preferable for the second material to use PE or another non-PET material.

After extruding the outer shell 18 and possibly cutting to length, the sleeve-like pieces are closed to form the container 5 and the fluid space 14, respectively. First, the connection 16 or the connecting piece 21 is attached, wherein a suitable material, such as PE or PET, which connects to the wall 15 and / or outer shell 18, is selected for the connecting piece 21.

After the connection piece 21 has been injection-molded or the connection 16 has been attached, the container 5 or fluid space 14 can be closed in the opposite end region 30; of course, this can also be done first, ie before the connection piece 21 or connection 16 is attached.

Filling the fluid space 14 of the container 5 with the fluid

4 can either be done either via the terminal 16, so the actual removal end, or on the bottom end portion 17. In the first case, the fluid space 14 is filled with the fluid 4 before the closure of the connection 16, in particular before the insertion of a closure part 23, and the closure part 23 is welded gas-tight to the connection piece 21 in order to close the connection 16. In the second case, the fluid 4 is filled before closing the wall 15 in the end region 17, in which case then the connection 16 at the other end of the container

5 is closed.

In particular, the container 5 can be used in the nebulizers or inhalers described in the following references or based on their principles: EP 1 236 517, EP 1 561 484, EP 1 562 094, EP 1 604 701, JP 2004-0283245, JP 2004-249208, JP 2004-283244, JP 2005/058421, US 2002/0153006, US 2003/0100964, US 2003/0127538, US 2004/0163646, US 2005/0034723, US 2005/0133029, US 2005/0172957, US 2005/0224076, US 2005/0268911, US 5,915,378, WO 03/041774, WO 2004/022128, WO 2004 / 039442, WO 2004/078244.

The closure part 23 of the container 5 has a septum 25 pierceable by a delivery tube 24 of the atomizer 13 and may additionally be closed by an optional seal 41 which is evident through the delivery tube 24.

The atomizer 13 is designed as a portable inhaler and works without propellant gas. When atomizing the fluid 4 or the medicament preparation, a respirable aerosol 43 is formed, which can be inhaled or inhaled by a user, not shown. In the atomizer 13, the container 5 is used with the fluid 4.

The atomizer 13 is provided with a pressure generator 26 for the promotion and / or atomization of the fluid 4, in particular in each case in a predetermined, optionally adjustable dosage amount.

In addition, the atomizer 13 or pressure generator 26 has a holder 27 for the container 5, an associated, only partially shown drive spring 28 with an associated, for unlocking manually operable locking element 29, preferably designed as a capillary conveyor tube 24, an optional valve, in particular Check valve 30, a pressure chamber 31 and a discharge nozzle 32 in the region of a mouthpiece 33 or other end piece. The Container 5 is clamped or latched by means of the holder 27, thus fixed in the atomizer 13 such that the delivery tube 24 dips into the fluid space 14 and / or is fluidically connected thereto.

During axial tensioning of the drive spring 28, the holder 27 with the container 5 and the delivery tube 24 is moved downwards and a dose of the fluid 4 is sucked out of the container 5 via the check valve 30 into the pressure chamber 31 of the pressure generator 26. The fluid space 14 (bag) collapses as a function of the removal of fluid 4, as indicated schematically by the dashed line in the lower region of the fluid space 14 in FIG. 4, for example. During the subsequent relaxation of the drive spring 28 after actuation of the blocking element 29 for atomization, the fluid 4 in the pressure chamber 31 is pressurized by the conveyor tube 24 is moved back up with now closed check valve 30 by the force of the drive spring 28 and now as Pressure stamp works. This pressure expels the fluid 4 through the discharge nozzle 32, where it is atomized into the respirable aerosol 43.

During the atomization process or stroke, the container 5 is moved back by the drive spring 28 to its original position. The container 5 thus performs a lifting movement during the tensioning process and during the sputtering process.

The atomizer 13 comprises an upper housing part 34 and a counter-rotating inner part 35 with an upper part

36 and a lower part 37, wherein on the inner part 35 a manually rotatable housing lower part 38 releasably secured by means of a retaining element 39, in particular attached thereto, is. The holding element 39 is designed such that accidental opening of the atomizer 13 or removal of the lower housing part 38 is excluded. In particular, to release the lower housing part 38, the retaining element 39 must be pressed against spring force. For insertion and / or replacement of the container 5, the lower housing part 38 is detachable from the atomizer 13.

The lower housing part 38 can be rotated relative to the upper housing part 34, wherein the inner part 35 is rotated. As a result, the drive spring 28 is tensioned in the axial direction via a gear not shown in detail, acting on the holder 27.

The atomizer 13 optionally has a device for forced ventilation of the container 5, in particular the outer shell 18, on. When clamping for the first time, the container 5 or the outer casing 18 pierces at the bottom, wherein an axially acting spring 40 arranged in the lower housing part 38 comes to rest on the bottom part 19 of the container 5, which with a piercing element 42 forms a bottom-side, in particular gas-tight, Seal for ventilation. Of course, remains at the piercing of the

Fluid space 14 (bag) with the fluid 4 and the wall 15 undamaged.

Upon removal of the fluid 4 via the delivery tube 24, the flexible fluid space 14 collapses. The ambient air can be compensated for pressure via the ventilation or piercing opening flow into the container 5.

To use the atomizer 13, the container 5 must first be used, for which purpose the lower housing part 38 is removed. Subsequently, the container 5 is inserted into the inner part 35. Here, a head-side opening or connecting takes place through the delivery pipe 24, which pierces the head-side seal 41 of the container 5 and is introduced through the connection 16 into the interior of the container 5 or fluid space 14. Subsequently, the lower housing part 38 is replaced. Now, the first-time tensioning of the atomizer 13 can take place.

Reference sign list

1. Feed line 29. Locking element

2. Valve device 30. Check valve

3rd Chamber 31. Pressure chamber

4. Fluid 32. Discharge nozzle

5. Container 33. Mouthpiece

6. discharge line 34. housing upper part

7. Valve device 35th inner part

8. Sensor 36. upper part v. 35

9. Vacuum pipe 37th lower part v. 35

10. Valve device 38. Housing base

11. Vacuum pump 39th holding element

12. Bypass 40th spring

13. Atomizer 41. Sealing

14. Fluid space 42. piercing element

15. Wall 43. Aerosol

16. Connection

17th end area

18. outer shell

19th bottom piece

20. Ventilation opening

21. Connector

22. Investment area

23. Closing part

24. Delivery pipe

25th septum

26. Pressure generator

27. Holder

28. Drive spring

Claims

claims

A method of testing the tightness of a container (5) filled with a fluid (4) in which a fluid component exiting the container (4) is detected using a sensor (8) responsive to the fluid component, the container ( 5) is located in a closed chamber (3) in which the exiting fluid component is collected over a predetermined period of time during which a carrier gas flow is supplied to the sensor (8) via a bypass (12) and after the passage of time the carrier gas flow through the chamber (3) is passed to supply the collected fluid component to the sensor (8), characterized in that during the period in which the fluid component leaving the container (5) is collected in the chamber (3), the chamber (3) is subjected to a vacuum.

2. The method according to claim 1, characterized in that the vacuum for a period of less than 60s, in particular less than 40s, preferably less than 30s and more preferably less than 15s is maintained.

3. The method according to claim 1, characterized in that predetermined climatic conditions are set.

4. The method according to claim 1 or 3, characterized in that the carrier gas stream is heated.

5. The method according to claim 1 or 3, characterized in that the carrier gas stream is humidified or dehumidified.

6. A device for checking the tightness of a container filled with a fluid (5), comprising a sensor (8) for detecting a leaking from the container (5) fluid component, wherein the container in a closed chamber (3) is arranged, the is connected via a valve control with a gas line and a bypass (12) for a carrier gas flow and with the sensor (8), characterized in that the chamber (3) with a vacuum pump (11) is connected.

7. Apparatus according to claim 6, characterized in that the sensor (8) is designed for detecting ethanol vapor.

8. Apparatus according to claim 6 or 7, characterized in that the sensor (8) is coupled to an evaluation and display unit which stores measured values, compares with limit values and outputs a visually and / or acoustically perceptible signal when a limit value is exceeded ,

9. Apparatus according to claim 6, characterized in that the interior of the chamber (3) is adapted to the size of the container (5).

A container, in particular for a nebulizer (13), for use in the method and / or in the chamber (3) of the device filled with an inhalable ethanolic drug formulation.

11. A container according to claim 10, characterized in that in an outer shell (18) an at least partially deformable wall (15) for forming a FIu- idraums (14) is used for receiving the drug formulation, wherein the fluid space (14) upon removal of the Drug formulation collapses and / or forms a deformable inner container and the wall (15) is at least partially detachable from the outer shell (18).

12. A container according to claim 11, characterized in that the wall (15) is formed as a multilayer film, in particular a metallic barrier layer and / or an outer layer of plastic.

13. A container according to claim 11 or 12, characterized in that the outer shell (18) and / or the wall (15) made of polyethylene terephthalate (PET) and / or polyethylene (PE) are made.

14. Container according to one of claims 11 to 13, characterized in that the outer shell (18) and / or the wall (15) with a connecting piece (21) and the outer shell (18) are connected to a bottom piece (19), wherein the connection piece (21) is provided with a closure part (23) associated with the fluid space (14), preferably by connecting or inserting a delivery element, in particular delivery tube (24), for removal of fluid (4).

15. An atomiser, preferably an inhaler, for a fluid (4) with a container (5) according to claim 10.