FI92171B - Method and apparatus for feeding into a container a drug suspension or solution in a pressurized propellant - Google Patents

Abstract

The application describes a method of introducing into a container a suspension or solution of a material in a propellant held under pressure, in particular a pharmaceutical material. The method comprises the steps of bringing a filling head (28) into communication with the container (C); introducing a quantity of such suspension or solution into the container through the filling head (28); introducing a quantity of high pressure propellant without any of the said material into the filling head (28), thereby to flush through any suspension or solution remaining in the filling head; and withdrawing the filling head from the container. An apparatus and a filling head (28) for carrying out the method are also described.

Description

92171

Method and apparatus for feeding a drug suspension or solution in a pressurized propellant to a container Förfarande ooh anordning för att i en behällare inmata en läkemedelssuspension eller -lösning i ett drivämne under tryck

The present invention relates to a method and an apparatus for feeding a material to be dispensed in the form of an aerosol into a container and to the propellant required therefor. The invention relates in particular to the supply of pharmaceutical materials to containers and the following description of the invention will focus on this. However, it is clear that the invention can be applied to other materials as well.

Pharmaceutical materials for conventional aerosol use are usually suspended in a mixture of at least two propellants, wherein at least one propellant has a sufficiently high boiling point to keep it liquid at room temperature and at least one has a low enough boiling point to keep it as a gas at room temperature.

For the sake of clarity, these are referred to in this description of the invention as liquid or low pressure propellant and gaseous or high pressure propellant, respectively. The pharmaceutical material is first suspended in the liquid propellant by stirring. Each aerosol container is then partially filled with this suspension. A certain amount of gaseous propellant is then added to each tank using either the cold filling method or the high pressure method. In the above, the filling step is performed at a temperature sufficiently below room temperature so that the gaseous propellant is liquid. Each container is then closed with a closure which includes an outlet valve through which the contents of the container can be dispensed later. In the high pressure method, the closure is attached to the tank before the gaseous propellant is fed and this propellant is later added to each tank by forcing it under pressure into the tank 921 71 2 through an outlet valve, which in this case actually acts as an inlet valve.

There is currently no satisfactory method of filling a container with a drug suspension or solution in a one- or multi-component propellant that is gaseous at room temperature. According to one aspect of the invention, it is an object to provide such a method and to provide an apparatus for carrying out the method.

Figures 1 and 2 of the accompanying drawings schematically show a typical known device for feeding a pharmaceutical material and a two-component propellant system to a container.

Figure 1 shows the filling of a suspension of pharmaceutical material in a liquid propellant into a container C. The container 1 contains a bulk storage of this suspension which is pumped by a pump 2 through a non-return or directional valve 3 to a metering cylinder 4 with a hole 5. From there the suspension travels to the filling end 8. through the non-return valve 9 and from there back to the container. The suspension thus remains in constant circulation. When a certain amount of suspension is to be transferred to the tank C, the tank is placed below the head 8 and the valves 3 and 9 are closed. The compressed air cylinder 6 is then used to force the piston therein downwards, whereby the pressure in the suspension between valves 3 and 9 increases to a level sufficient to open the valve from the filling head 8 and cause the suspension to move from the filling head to the tank C. The valves 3 and 9 are then opened and the valve 8 is closed and when the piston in the cylinder 6 is pulled to its initial position, the cylinder 4 is refilled from the container 1. The movement of the filling nozzle into contact and release from contact with each can is effected by the piston and cylinder device 7. The filling head 8 is arranged to operate only when in contact with container C.

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The device of Figure 1 feeds a suspension of pharmaceutical material in a liquid propellant to the container C and, after the aerosol valve has been pressed into the can C, the device shown in Figure 2 drives it and feeds the gaseous propellant. The device according to Figure 2 is formed of components which are in principle substantially the same as the corresponding components according to Figure 1, except that it does not have any part corresponding to the non-return valve 9, nor does it have any recirculation. The components shown in Figure 2 are indicated by reference numerals corresponding to those otherwise used in Figure 1, but with the addition of 10. The container 11 contains only a gaseous propellant which is at a sufficient pressure to be liquid and does not contain any pharmaceutical material.

When the device according to Fig. 2 is in operation, a small amount of gaseous propellant escapes each time the filling head 18 is lifted from the tank C. This does not have any particular consequences, provided that the amount of propellant lost in this way is small.

However, this feature of the device of Figure 2 means that if it were to supply a suspension or solution of pharmaceutical material in a high pressure propellant to the container, the device would be completely unusable. It can be seen that if the container 11 contained such a suspension or solution, each time the filling head 18 was lifted out of the container, a certain amount of this suspension or solution would escape. This would pose a risk to workers who use it, and where the pharmaceutical material in question would be expensive, it could also be a significant financial loss. In addition, the escaped pharmaceutical material would tend to deposit and accumulate in the surrounding portion of the device and on the outer surface of the container itself, which would cause cleaning problems. In theory, the first of these problems could be avoided by surrounding the device of Figure 2 with an exhaust system, although this would involve considerable costs.

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The other two problems could not be avoided even with such an exhaust system.

According to the present invention, there is provided a method of feeding a drug suspension or solution in a pressurized propellant to a container, which method is characterized by the features set forth in the characterizing part of claim 1.

According to the present invention, there is further provided an apparatus for feeding a drug suspension or solution in a pressurized propellant to a container, which apparatus is characterized by the features set forth in the characterizing portion of claim 6.

The invention also provides a filling head for use in feeding a suspension or solution of material in a pressurized propellant to a container, the filling head comprising an outlet passage adapted to be used in communication with the container; first and second inlet passages, each of which communicates with said outlet passage through a common flow path, through the inlet passages of which, in use, a propellant containing said material and a high-pressure propellant without said material are fed, respectively; and means for optionally closing the first and second inlet ducts so that the liquid entering each inlet duct cannot flow out along the other.

In accordance with all these aspects, it is an advantageous and easy-to-use invention when the propellant without suspension or solution is the same propellant as the one in which the material is held. The propellant is preferably 1,1,1,2-tetrafluoroethane (also known as "134a" propellant).

The material to be filled into the container is preferably a pharmaceutical agent, for example salbutamol or beclomethasone dipro-; propionate.

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Preferred embodiments of the invention are explained below by way of example with reference to Figures 3, 4A-4D and 5 of the accompanying drawings, in which:

Figure 3 schematically shows a device according to the invention.

Figures 4A-4D show an embodiment of a filling head which can be used in the device according to Figure 3.

Figure 5 shows another embodiment of a filling head that can be used in the device of Figure 3.

The device according to the invention shown in Figure 3 actually resembles in some way the combination of the devices according to Figures 1 and 2, but has a new common filling head. The components shown in Figure 3 are indicated by reference numerals corresponding to those in Figure 1, but with the addition of 20 or 30. Container 21 contains a pharmaceutical material suspension in a high pressure propellant and container 31 contains only that propellant in storage, i.e. no pharmaceutical material is suspended in it. Although the vessel 31 in this case contains the same propellant, it is of course possible to use another high-pressure propellant. In addition, the container 21 may contain a pharmaceutical material solution instead of a suspension.

Figures 4A-4D show in more detail and on a larger scale the filling head 28 used in the device of Figure 3. The end includes a substantially cylindrical body 40 with the lower end adapted to engage the upper end of the aerosol container C in use. The pipe section 43 is mounted to slide inside the body 40. The tubular portion 43 has a wide base portion 44, a narrower body portion 45, and an even narrower neck portion 46. In this context, "wide" and "narrow" refer to diameters.

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The neck portion 46 of the tubular portion 43 protrudes upside down through the bottom of the inverted cup 47, the cup wall of which surrounds the body portion 45. The body portion 45 is thus slidable into the cup 47.

The base 44 of the tubular portion abuts the inwardly extending edge 50 of the body 40. The outwardly projecting edge 51 of the cup 47 rests on the inner shoulder 52 of the body 40. The tubular post 55 is helically attached to the body 40 so that its lower edge engages the edge 51 of the cup 47. about.

The ring 56 is screwed onto the column 55 so that it rests above the cup 47. The neck portion 46 of the tube portion 43 just protrudes into the ring 56. A sliding seal 58 is arranged between the ring 56 and the neck portion 46. Rubber O-ring seals 59, 60 are also provided between the ring 56 and the post 55 and the base portion 44 of the portion 43 to which the container C nozzle fits ( explained below).

The ring 56 forms an upwardly conical seat 62 for a correspondingly shaped plug 63. The plug 63 is pressed into the seat by a compression spring 64, the upper end of which acts against the downwardly directed edge 65 of the column 55.

Above the edge 65 are opposite inlet channels 69, 70 which communicate from the outside of the column 55 to the inside thereof and thus further into the pipe section 43 and further into the container. The inlet pipes 72, 73 are arranged in the inlet ducts 69, 70 in the corresponding order and sealed to them by O-ring seals 74, 74 '.

A ball bearing 75 is interposed between the inlet passages, which may close against either O-ring seal 74, 74 'to form a valve. As explained below, the ball bearing 75 is forced either against the O-ring 74 to close the inlet channel 69 or against the O-ring 74 'against the inlet channel. 70 to close.

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Above the inlet passages 69, 70, the column 55 forms a circular seat for a piston (not shown) which presses the filling head down against the container C.

The inlet passage 69 is connected to a pipe which conveys the suspension from the dosing cylinder 24 to the non-return valve 29. The inlet duct 70 is connected to the outlet of the propellant-containing dosing cylinder 34.

At its rest, the suspension S flows along the tube from the metering cylinder 24 to the non-return valve 29 without entering the column 55, as this is prevented by a ball bearing valve 75 forced against the O-ring 74 by the overpressure of the propellant P in the tube from the cylinder 34. When it is desired to supply a certain amount of suspension to the container through the head 28, as will be explained immediately below, the valves 23 and 29 are closed and the cylinder 26 acts to force the piston therein to protrude.

At this point, the filling head 28 has moved downwardly onto the container C as shown in Figure 4B. The nozzle of the container rests against the O-ring seal 60 and when lowering the head, the nozzle forces the tube portion 43 into the cup 47 and the ring 56 until the edge 50 of the body 40 abuts the edge of the container. In this position, the neck portion 46 of the tube portion 43 has protruded through the ring 56 and pushes the plug 63 out of the seat 62 against the action of the spring 64. It is now possible to establish a connection between the interior of the column 55 and the interior of the pipe section 43.

The increase in pressure of the suspension in the metering cylinder 24 caused by the operation of the cylinder 26 is sufficient to overcome the force of the propellant acting against the ball-bearing valve 75 and thus the suspension can flow from the inlet duct 69, the column 55 and the tube portion 43 and further into the tank. The inlet passage 70 remains closed because the pressure of the suspension forces the ball-bearing valve 76 against the O-ring 74 '. In this case, the suspension 8 92171 cannot move from the input channel 69 to the input channel 70 and thus does not contaminate the input channels 70.

The next step in filling the container is to cause a certain amount of propellant without the pharmaceutical material suspended therein to flow to the head 28 through the interior of the column 55 and the tube section 43 and from there to the container. This is accomplished by closing the valve 33 and using a pneumatic cylinder 36. The resulting increase in propellant pressure is sufficient to move the ball bearing valve 75. The propellant cannot now move from the open inlet passage 70 to the inlet passage 69 because the ball bearing valve 75 has protruded against the O-ring 74. This position is shown in Figure 4C.

The supply of propellant through the inlet channel 70 while the head 28 is still against the tank C flushes out the suspension still inside the column 55 and the pipe section 43. In this case, when the head 28 is lifted out of the aerosol container after the completion of the filling step, as shown in Fig. 4D, the material escaping from the lower end of the head is essentially only a propellant and no pharmaceutical material can escape into the environment.

Figure 5 shows an alternative embodiment of the filling head 28 used in the device of Figure 3. The end of Figure 5 has a substantially cylindrical body 80, the lower end of which is adapted to engage the upper end of an aerosol container (not shown in this figure) in use. The ring 81 is arranged to slide longitudinally from the body 80 and has an inwardly directed flange 82 on which rests the lower end of the tube part 83. The upper end of the tubular portion 83 is surrounded by an upside down cup 84. The cup 84 is in turn surrounded by the annular lower portion of the column 85. The ring member is screwed to the body 80 to secure the cup 84 in place and the seal is formed by O-ring seals 86 and a slide seal 87. The tube member 83 is forced to engage the flange 82 by a compression spring. 88, the upper end of which is pressed against the surface of the cup 84.

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The column 85 has a pair of opposite inlet passages 89 and 90. The inlet passage 89 is connected to a pipe which carries the suspension from the dosing cylinder 24 to the non-return valve 29. The inlet duct 90 is connected to the outlet duct of the propellant-containing dosing cylinder 34. The inlet passages 89 and 90 communicate with the pipe section 83 via respective poppet valves 91 and 92 which are compressed by their compression springs 93 and 94 to their closed positions.

As in the embodiment of Figure 4 and in its resting state, the suspension flows along the tube from the metering cylinder 24 to the non-return or directional valve 29 without protruding into the tube portion 83, which is blocked by the valve 91. If a certain amount of suspension is fed to the tank through the head 28, valves 23 and 29 to force the piston down there. The resulting increase in the pressure of the suspension in the metering cylinder 24 is sufficient to overcome the pressure holding the valve 91 is sufficient to overcome the force of the spring 93 holding the valve 91 and the suspension can thus flow from the inlet duct 89 through the interior of the pipe section 83 into the tank. Valve 92 remains closed and, in fact, the effectiveness of the closure it forms only increases because the end 95 of valve 91 engages the end 96 of valve 92. Thus, the suspension cannot flow from inlet passage 89 to inlet passage 90 and thus contaminate the inlet passage 90.

The next step in filling the container is, as in the previous embodiment, feeding the propellant without suspended pharmaceutical material to the end 28, through the pipe section 83 and further into the container. This is accomplished by closing the valve 33 and using a compressed air cylinder 36. The resulting increase in propellant pressure is sufficient to open the valve 92 to allow the propellant to pass through the head 28. The propellant cannot pass from the inlet channel 90 to the inlet channel 89 due to the operation of the valve 91.

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The supply of propellant through the inlet passage 90 while the head 28 is still against the tank flushes out the suspension inside the pipe section 83 and immediately above the pipe section. Accordingly, this embodiment also achieves that when the head 28 is lifted off the aerosol container after the filling step is completed, the material escaping from the lower end of the head is substantially completely propellant and no pharmaceutical material enters the environment.

Claims (8)

A method of feeding into a container (C) a drug suspension or solution in a pressurized fuel, which suspension or solution is circulated in a conduit having a filling head (28), characterized in that the filling head (28) brought into contact with the container (C); said suspension or solution is fed into the container (C) via the loading head (28); said non-high pressure propellant drug is fed into the loading head (28) while still in communication with the container (C), whereby any required suspension or solution is rinsed; which loading head (28) allows feeding partly of suspension or solution only and partly of propellant only, when raised; and the loading head is detached from the container. Method according to claim 1, characterized in that the said drug containing the propellant and the said non-propellant drug are the same. 3. A process according to claim 1 or 2, characterized in that the propellant is 1,1,1,2-tetrafluoroethane. 4. A process according to claim 3, characterized in that the drug is salbutamol. 5. A process according to claim 3, characterized in that the drug is beclomethasonide propionate. Device for feeding in a container (C) a drug suspension or solution in a pressurized propellant, characterized in that it comprises a circulation line for the suspension or solution, which line has a loading head (28) arranged to be connected 3. with a container (C) and detached therefrom; means for feeding the suspension or solution along a conduit in a first entrance (69, 89) to the loading head (28); means for supplying drugs not containing high-pressure propellant in a second entrance (70, 90) to the filling head (28), wherein the filling head (28) includes a joint for suspension or solution and for fuel only, each of which the entrance channel (69, 70, 89) , 90), is connected to the joint, and a valve system (75, 91, 92), for closing the input (69, 89) for suspension or solution and closing the input (70, 90) for the propellant alone, wherein at each respective moment only one of said input channels 69, 70, 89, 90) is connected to the hinge, the loading head being arranged so that the drug not containing the propellant stream flushes out any suspension or solution remaining in the hinge. 7. Device according to claim 6, characterized in that the valve part comprises a valve member 75) which moves between the position (69) for suspension or solution closing position and the position (70) for the propellant closing position only. 8. Device according to claim 7, characterized in that the valve part is a spherical part (75). Device according to Claim 7, characterized in that the valve member includes valve means (91, 92) in respective inputs (89, 90), the input channels (89, 90) being opposite each other and the valve means (91, 92) being arranged so as to that when one is open, this pushes the other more forcefully than the previous one into the closing position.