JPH03212395A - Method and device - Google Patents

Abstract

PURPOSE: To prevent pecuniary losses accompanying escape of a suspension or solution by introducing a high-pressure propellant into a filling head in drawing in the suspension or solution through the filling head into the container and flushing through the suspension or solution remaining in the filling head. CONSTITUTION: A container 21 holds a suspension in which a pharmaceutical is suspended in a high-pressure propellant and a container 31 holds a unit supply of the same propellant independently, that is, in a state without the pharmaceutical in suspension. When a suspension is drawn into the container through the head 28, valves 23 and 29 are closed and a cylinder 26 is worked to move a piston downward. In this stage the filling head 28 is brought down over the container C. In the next stage of filling the container, propellant in which no pharmaceutical is in suspension is passed through the interior of a pillar 55 and that of a tubular member 63 and passed to the head 28 in being drawn into the container. To effect this passage a valve 33 is closed and a pneumatic cylinder 36 is put in action. After completion, the head 28 is raised from the aerosol container.

Description

BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a method and a device for introducing into a container a material to be dispensed in the form of an aerosol and a propellant therefor. In particular, the present invention relates to introducing a drug into a container, and the following description will focus on this. However, it will be appreciated that the invention may be applied to other materials.

BACKGROUND OF THE INVENTION Traditionally, drugs to be administered in aerosol form are suspended in a mixture of at least two propellants, at least one of which is sufficiently hot to be liquid at room temperature. at least one of the propellants has a boiling point low enough to be gaseous at room temperature.

For convenience, these will be referred to below as liquid propellants or low-pressure propellants and gaseous propellants or high-pressure propellants, respectively. First, the drug is suspended in a liquid propellant by a mixing operation. Each aerosol container is then partially filled with this suspension. A quantity of gaseous propellant is then introduced into each of the containers using either a cold fill method or a high pressure fill method. In the low-temperature filling method, in order to keep the gaseous propellant in a liquid state, the filling operation is performed at a temperature sufficiently lower than room temperature.

Each container is then closed with a closure member provided with an outlet valve.

The contents of the container can subsequently be dispensed through this outlet valve. In the high-pressure filling method, a closure member is attached to the container before introducing the gaseous propellant, and this is followed by
Propellant is introduced into each container by forcing it into the container through an outlet valve. During this operation, the outlet valve effectively acts as an artificial valve.

There is currently no satisfactory method for filling containers with suspensions or solutions of drugs in gaseous monocomponent or multicomponent propellants at room temperature. One object of the invention is to provide such a method and to provide an apparatus for implementing such a method.

1 and 2 are schematic diagrams of typical known devices for introducing drug and two-component propellant into a container.

FIG. 1 shows the introduction into container C of a suspension of drug in liquid propellant. The container 1 contains a bulk supply of suspension, which is conveyed by a pump 2 through a reverse valve 3 to a metering cylinder 5 provided with a hole 5 . From here the suspension is sent to the filling head 8. In the absence of a filling operation, the suspension flows through the head 8 to the check valve 9 and from there back into the container 1. That is, the suspension is constantly circulating. If a certain amount of suspension is introduced into the container C, the container is placed under the head 8 and the valve 3
and 9 are closed. The pneumatic cylinder 6 is then actuated, pushing the piston downwards to release the pressure of the suspension trapped between valves 3 and 9, opening the valve of the filling head 8 and allowing the suspension to flow into the container C into the filling head. raised to a value sufficient to be sent from Valves 3 and 9 are then opened and the valve of filling head 8 is closed, when cylinder 6
The piston inside is raised to its initial position and the cylinder 4 is filled with the container 1. The filling nozzle is connected to and removed from the respective container by means of a cylinder device 7. The filling head 8 is operated only when feeding the container C.

By means of the apparatus shown in FIG.
Caulk and fix. The apparatus of FIG. 2 operates to introduce gaseous propellant into this can C. The device of FIG. 2 is formed of substantially similar components to the corresponding components of FIG. 1, except that there is no component corresponding to check valve 9 and no recirculation is provided. The components shown in Figure 2 include:
Reference numbers corresponding to those used in FIG. 1 plus 10 are provided. The container 11 contains only the gaseous propellant under sufficient pressure to keep it in liquid form;
Contains no drugs.

When the apparatus of FIG. 2 is operated, the filling head 18 is moved into the container C.
A small amount of gaseous propellant escapes each time it is lifted. If the amount of propellant lost in this way is small, it is almost negligible.

However, this feature of the operation of the device of Figure 2 is extremely unsatisfactory when used to introduce into a container a suspension or solution of a drug in a high-pressure propellant. It means that there is. If the container 11 contains such a suspension or solution, a large amount of suspension or solution will escape each time the filling head 18 is lifted from the container C.

This would pose a risk to the personnel engaged in this operation and, if the drugs involved are expensive, could result in significant financial losses. Furthermore, the escaped drug tends to settle around the device and on the outside of the container itself, creating cleaning problems. The first of these problems could in principle be avoided by surrounding the device of FIG. 2 with an exhaust system, but this would be quite expensive.

Two other problems cannot be avoided with such an exhaust system.

[Detailed description of the invention]

According to the invention, there is provided a method for introducing into a container a suspension or solution of a material in a propellant, which is maintained under pressure, the filling head a step of introducing a certain amount of the suspension or solution into the container through the filling head; and a step of communicating the filling head with the container in order to wash out the suspension or solution remaining in the filling head. A method is provided having the steps of: introducing a quantity of high-pressure propellant free of any material into a filling head; and retracting the filling head from a container.

According to the present invention, there is provided a device for introducing into a container a suspension of a material in a propellant or a solution of a material in a propellant, which is maintained under pressure. a filling head adapted to be communicated with and removed from the container, a device for supplying a quantity of suspension or solution to the filling head, and a quantity of high pressure propellant containing no material; and a device for feeding a filling head, the filling head being configured such that a stream of propellant free of any material washes away any suspension or solution remaining in the filling head. .

Furthermore, the present invention provides a method for use in introducing into a container a suspension or solution of a material in a propellant, which is maintained under pressure. a filling head having, in use, an outlet in communication with the container; and first and second inlets each communicating with the outlet through a common passage; agent and material-free propellant are introduced through these inlets, respectively, and further for selectively closing the first and second passages so that fluid entering either inlet does not exit the other inlet. A filling head having an apparatus is provided.

In all aspects of the invention, it is advantageous and convenient if the unsuspended and undissolved propellant is the same propellant as the drug-containing propellant. Advantageously, the propellant is propellant r
1, known as 134aJ. ■.

(2) 2-tetrafluoroethane.

Preferably, the material filled into the container is a drug, such as Salbutamol or beclomethasone dipropionate.

Embodiments of the invention will be described by way of example below with reference to the accompanying drawings, in which: FIG.

EXAMPLE The apparatus according to the invention shown in FIG. 3 has in practice a similar combination to the apparatus of FIGS. 1 and 2, but with a common filling head of novel design.

The components shown in FIG. 3 are given reference numbers corresponding to the reference numbers used for the components shown in FIG. 1 plus 20 or 30. Container 21 contains a suspension of a drug in a high-pressure propellant, and container 31 contains a supply of the same propellant alone, ie without drug suspended therein. There is. In this embodiment, the containers 31 contain the same propellant, but of course different types of high-pressure propellants may be used. Furthermore, the container 21 may contain a solution of the drug instead of a suspension.

4(a)-4(d) show in more detail and in enlarged view the fill head 28 for use in the apparatus of FIG. 3. FIG. This head has a generally cylindrical body 140, the lower end of which is adapted to be engaged on the upper end of the aerosol container C in use. A tubular member 43 is slidably mounted within the body 40. Tubular member 43 has a large diameter base portion 44, a small diameter body portion 45, and an even smaller diameter neck portion 46. As used herein, "large diameter" and "small diameter" refer to diameter.

A neck portion 46 of tubular member 43 passes through the base of a downwardly directed cup 47 whose wall surrounds body portion 45 . The body portion 45 is thus able to slide within the cup 47.

The base portion 44 of the tubular member abuts an inwardly extending lip 50 of the body 40 . An outwardly extending lip 51 of the cup 47 rests on an inner shoulder 52 of the body 40.

The lower edge of the tubular pillar 55 is the lip 51 of the cup 47.
It is screwed onto the main body 40 so as to engage upwardly. Pillar 55 thus fits around the wall of cup 47.

Ring 56 is threaded into pillar 55 so that it is mounted above cup 47. Tubular member 4
The neck portion 46 of No. 3 is adapted to fit snugly into the ring 56. A sliding seal 58 fits between ring 56 and neck portion 46.

Additionally, a rubber O-ring seal 59.60 is attached to ring 5.
6 and the pillar 55, and on the base portion 44 of the member 43 into which the nozzle of the container C fits (see below)
.

The ring 56 constitutes an upwardly tapered seat 62 for a correspondingly formed plug 63. plug 63
is pressed against the seat by a compression spring 64, the upper end of which rests against the inward lip 65 of the pillar 55.

Above the ring 65 there are opposed inlets 69,70 connecting the outside and the inside of the pillar 55 and thus the inside of the tubular member 43, i.e. the container.

The inlet tubes 72,73 are each fitted with a port 69,70 and sealed with an O-ring seal 74,74-.

A ball bearing 75 is provided between the inlets, which engages one of the O-rings 74, 74- to form a valve. As explained below, the ball bearing 75 is pressed against the O-ring 74 to seal the inlet 69 or against the O-ring 74' to seal the inlet lower 0.

The pillar 55 connects the circular seat of the piston (not shown) to the inlet 69 which acts to push the mating head down onto the container C.
．． Formed above 70.

The inlet 69 allows the suspension to pass from the metering cylinder 24 to the check valve 29.
It is connected to a conduit that transports the The input lower 0 is connected to the outlet of a metering cylinder 34 containing propellant.

In the rest state, the suspension S flows along the line from the metering cylinder 24 to the check valve 29 without entering the pillar 55. The entry of the suspension into the pillar 55 is prevented by the ball bearing 75 which is pressed against the O-ring 74 by the excessive pressure of the propellant P in the line from the cylinder 34 . If it is desired to introduce a certain amount of suspension into the container 5 through the head 28, the valves 23 and 29 are closed and the cylinder 26 is actuated to move the piston downward, as explained below. let

At this stage, the filling head 28 has been moved downwardly onto the container C as shown in FIG. 4(b). The nozzle of the container abuts the O-ring seal 60 and as the head is lowered, the nozzle forces the tubular member 43 into the cup 47 and ring 56 until the lip 50 of the body 40 abuts the rim of the container. In this position, the neck portion 46 of the tubular member 43 passes through the ring 56 and pushes the plug 63 out of the seat 62 against the action of the spring 64. Communication between the interior of the pillar 55 and the tubular member 43 is now possible.

The increase in pressure of the suspension in the metering cylinder 24 causing actuation of the cylinder 26 is sufficient to overcome the force of the propellant acting on the ball bearing valve 75 and the suspension thus flows from the inlet 69 to the pillar 55. and can flow into the container through the interior of the tubular member 43. Inlet lower 0 remains closed because the pressure of the suspension forces ball bearing valve 756 against O-ring 74'. Thus, the suspension cannot pass from the inlet 69 to the lower inlet 0 and contaminate the lower inlet 0.

The next step in filling the container is to pass a quantity of propellant with no drug suspended through the interior of the pillar 55 and tubular member 43 to the head 28 and thus into the container. This is done by closing valve 33 and activating pneumatically actuated cylinder 36. The increase in propellant pressure that causes this is sufficient to displace the ball bearing valve 75. Propellant cannot pass from the inlet lower 0, which is open in this case, to the inlet 69. this is,
This is because the ball bearing valve 75 is pressed against the O-ring 74. This position is shown in FIG. 4(C).

Inject the propellant with the head 28 placed on the container and lower 0.
The suspension remaining inside the pillar 55 and the tubular member 43 is washed away by introducing it through the tube. Therefore, when the head 28 is lifted from the aerosol container after the filling operation is completed, as shown in FIG. do not.

FIG. 5 illustrates a modification of the filling head 28 for use in the apparatus of FIG. The head shown in Figure 5 has a generally cylindrical body 80, the lower end of which is adapted to engage over the upper end of an aerosol container (not shown in Figure 5) during use. . A ring 81 is longitudinally slidably mounted within the body 80. Ring 81 has an inwardly directed flange 82 on which the lower end of tubular member 83 rests. The upper part of the tubular member 83 is surrounded by a downwardly directed cup 84. Also, this cup 84
is surrounded by the annular lower part of the pillar 85. This annular portion is threaded onto the body 80 and sealed by an O-ring seal 86 and a sliding seal 87 to hold the cup 84 in place. The annular member 83 is pressed against the flange 82 by a compression spring 88 in a fixed state. The upper end of the spring 88 is in contact with the surface of the cup 84.

Pillar 85 has a pair of opposed inlets 89 and 90. The inlet 89 is connected to a line conveying the suspension from the metering cylinder 24 to the check valve 29 . The inlet 90 contains propellant and is connected to the outlet of the metering cylinder 34. Inlets 89 and 90 communicate with the interior of tubular member 83 via poppet valves 91 and 92, which are biased into closed positions by compression springs 93 and 94, respectively.

As in the embodiment of FIG. 4, in the rest state the suspension flows along the conduit from the metering cylinder 24 to the check valve 29 without entering the interior of the tubular member 83. Entry of the suspension into the interior of the tubular member 83 is prevented by the valve 9
1 is prevented. When a certain amount of suspension is to be introduced into the container via the head 28, the valves 23 and 29 are closed and the cylinder 26 is actuated to move the piston downward within the cylinder. The increase in the pressure of the suspension in the metering cylinder 24 due to this movement of the piston is sufficient to overcome the force of the spring 93 holding the valve 91 closed, and the suspension is thus forced out of the inlet 89. It flows into the container through the interior of the tubular member 83. Valve 92 remains closed and the effectiveness of the seal provided by valve 92 is increased by head 95 of valve 91 engaging head 96 of valve 92.

Thus, suspension cannot pass from inlet 89 to inlet 90 and contaminate inlet 90.

The next step in filling the container, similar to the embodiments described above, is to introduce a quantity of propellant, without any drug suspended therein, into the head 28 and thus into the container through the tubular member 83. This is done by closing valve 33 and activating pneumatic cylinder 36. The resulting increase in propellant pressure is sufficient to open valve 92 and inject propellant through head 28 . The propellant is supplied by valve 9.
1, it is not possible to pass from the inlet 90 to the inlet 89.

With the head 28 placed on the container, the propellant is introduced into the inlet 90.
By introducing the tube through the tubular member 83, the remaining suspension inside the material 83 and in the space directly above the tubular member is washed away. Therefore, in this embodiment, when the head 28 is lifted from the aerosol container after the filling operation is completed, substantially all of the material escaping from the lower end of the head is propellant and no drug escapes.

[Brief explanation of drawings]

1 and 2 are schematic diagrams of typical known devices for introducing drug and two-component propellant into containers; FIG. 3 is a schematic diagram of the device of the present invention; 4(a) to 4(d) are diagrams of one embodiment of a filling head used in the apparatus of FIG. 3, and FIG. FIG. 6 is a diagram of another embodiment of the head. 21.31... Container, 28... Filling head, 40.
...Body, C...Aerosol container, 43...Tubular member, 44...Base part, 45...Body part, 46
...Neck part, 47...Cup, 50.51...
・Lip, 52...Inner shoulder, 55...Tubular pillar, 56...Ring, 58...Sliding seal, 59°60...0-ring seal, 62...Seat, 63 ···plug.

Claims (1)

[Claims] 1. A method in which a suspension of a certain material in a propellant or a solution of a material dissolved in a propellant is introduced into a container under pressure, the method comprising: a step of communicating a filling head with a container; a step of introducing a certain amount of said suspension or solution into the container through said filling head; introducing a quantity of high-pressure propellant free of said material into the filling head while in communication with the container; and retracting the filling head from the container. 2. The method of claim 1, wherein the propellant containing said material and the propellant containing no said material are the same. 3. The method according to claim 1 or 2, wherein the propellant is 1,1,1,2 tetrafluoroethane. 4. The method of any one of claims 1, 2, and 3, wherein the material is a drug. 5. The method of claim 4, wherein the drug is salbutamol. 6. The drug is beclomethasone dipropionate;
The method according to claim 4. 7. A device for introducing a suspension of a material in a propellant or a solution of a material in a propellant into a container, which is maintained under pressure, and is connected to or connected to the container. a filling head adapted to be removed or removed from the filling head; a device for supplying a quantity of said suspension or solution to said filling head; and a filling head for supplying a quantity of high-pressure propellant free of any of said material; and a filling head configured such that the flow of propellant free of any of the material washes away any suspension or solution remaining in the filling head. 8. The filling head has a passage for the suspension or solution and for the propellant alone, an inlet for the suspension or solution, and an inlet for the propellant alone, each inlet communicating with the passage. and a valve movable between a position closing the inlet for the suspension or solution and a position closing the inlet for propellant alone, such that only one of the inlets communicates with the passageway at any given time. 8. The device of claim 7, further comprising a member. 9. The device of claim 8, wherein the valve member is a spherical member. 10. The filling head has a passage for the suspension or solution and for the propellant alone, an inlet for the suspension or solution, and an inlet for the propellant alone, each inlet communicating with the passage. and further comprising a valve at each inlet, the inlets facing each other, and the valve members configured such that when one is open, the open valve member further pushes the other valve member into the closed position. 8. The device of claim 7, wherein the device is configured to. 11. A filling head for use in introducing into a container a suspension or solution of a material in a propellant, which is maintained under pressure. an outlet which, in use, is in communication with the container; and first and second first and second outlets, each communicating with said outlet via a common passageway.
inlets, and in use, a propellant containing said material and a propellant without said material are respectively introduced through these inlets, further provided that fluid entering either inlet does not exit from the other inlet. A filling head having a device for selectively closing said first and second passages. 12. The filling head of claim 11, having a valve member for alternately closing the first and second inlets, the valve member being a spherical member. 13. Each of the first and second inlets has a valve member, the inlets face each other, and the valve member is configured such that when one of the inlets is closed, the closed valve member closes the other valve member. 12. A filling head as claimed in claim 11, configured to further push the member into its closed position.