WO1997029954A1

WO1997029954A1 - Apparatus for filling of cylinder ampoules

Info

Publication number: WO1997029954A1
Application number: PCT/DK1997/000055
Authority: WO
Inventors: Jimmy Bagge
Original assignee: Novo Nordisk A/S
Priority date: 1996-02-16
Filing date: 1997-02-10
Publication date: 1997-08-21
Also published as: AU1766297A

Abstract

In a filling station for topping up cylinder ampoules with a liquid supplied through a tubing controlled by a solenoid valve an upper part of the ampoules in the station is monitored by a video camera from which a picture signal is transmitted to a picture processing and calculating unit in which the position of the surface of the liquid in each ampoule, the position of the upper edge of this ampoule and the distance between the surface and the upper edge of said ampoule are currently calculated. It is further currently calculated when the surface of the liquid in the ampoule in question will reach the upper edge of this ampoule, and a signal is generated which causes a closing of the solenoid valve to stop the flow of liquid to said ampoule at the moment when the liquid is previewed to reach the upper edge of the ampoule.

Description

Apparatus for filling of cylinder ampoules.

The invention relates to an apparatus for filling cylinder ampoules of the kind comprising a cylindric tube which has a first and a second end, the first end being end closed by a piston and at the second end having a neck part terminated by a circumferential flange against which a rubber membrane is pres¬ sed sealingly by a cap having means gripping behind the flange.

Such ampoules are commonly filled with a liquid medicine preparation and are used in pen shaped injection devices by which set doses of the preparation may be injected until the ampoule is empty.

The filling of the ampoules are performed in a sterile zone in which a number of operating stations are disposed. To perform the filling quickly and precise the filling is often made in three steps. First about 40% of the content is by a maximal speed filled into the ampoule, thereafter the next 40% is added more slowly to prevent formation of foam, and finally the ampoule is topped up relatively slowly with the last 20% of the liquid.

The measuring of the amount of liquid filled in each ampoule is obtained by using very precise volumetric pumps for each of the filling steps. To obtain a reasonable throughput for the filling machine a number of ampoules, e.g. six, are filled concomitantly in each operating station. As each ampoule must be allocated its own pump in each station, a large number of pumps must be provided in the sterile zone. Such pumps are expensive and bulky. Piston pumps are difficult to clean and peristaltic pumps are difficult to make precise.

In WO 83/0335 the above problem is solved by supplying the liquid to each filling station through tubings which are each provided with an electromagnetic valve which may block the passage through the tubing in question by exertion of a pressure on the outer wall of the tubing to bring this tubing into a flattened condition in which its bore is closed. The measuring of the amount of liquid filled into each ampoule is obtained by positioning each ampoule on a weighing device by which the weight of the liquid filled into the cell may be currently measured. When a set weight is detected by the weighing device, it gives off a signal to the valve and the supply to the ampoule in question is stopped.

By filling cylinder ampoules of the kind initially mentioned it is more important that the ampoule is filled exactly to the edge of the neck part so that no or at least only very small air bubbles are left in the ampoule when the rubber membrane is sealed against upper surface of the flange. On the other hand the filling must not go over the edge so that excessive liquid is pressed out under the membrane when it is sealed to the upper surface of the flange. It is more important that these conditions are complied with than it is that an exact amount of liquid is filled into the ampoule as the dosing of the medicine takes place in the pen syringe in which the ampoule is used. The amount of liquid in the ampoule, which amount must of course at least be the amount stipulated for said ampoule, is set by the positioning of the piston closing the first end of the ampoule. As the space inside the ampoules may show minor variations from ampoule to ampoule, a precise measuring of the volume or the weight of the amount filled into the ampoule will not be sufficient to ensure a filling to and only to the edge of the flange of the neck part.

It is the object of the invention to provide a method and an apparatus by which a correct filling, i.e. a filling to the edge and only to the edge of the flange, is obtained.

This may be obtained by a filling station for topping up cylinder ampoules with a liquid supplied flow through a tubing controlled by a solenoid valve, which filling station is characterized in that an upper part of the ampoule in the station is monitored by a video camera from which a picture signal is transmitted to a picture processing and calculating unit in which the position of the surface of the liquid in the ampoule, the position of the upper edge of this ampoule and the distance between the surface and the upper edge of the ampoule are currently calculated, and wherein it is currently calculated when the surface of the liquid will reach the upper edge of the ampoule, and a signal is generated which causes a closing of the solenoid valve to stop the flow of liquid to the ampoule at the moment when the liquid is previewed to reach the upper edge of the ampoule.

By this filling station the parameter monitored is the very parameter of interest, i.e. the distance of the surface from the upper edge of the ampoule, and not a derived parameter, such as the volume or the weight of liquid filled into the ampoule. This is advantageous as the derived parameters cannot take into account variations in the volume of ampoule, e. g. due to variations from ampoule to ampoule of the position of the piston forming the bottom in the ampoule.

In the calculation unit data representing a bundle of curves may be stored, each curve representing connected values of surface distances from the upper edge of the ampoule and topping up time by a specific flow of liquid.

The remaining topping up time may currently be defined by detecting the liquid surface positions in two consecutive video frames. As the time spacing of the video frames is known it is possible to estimate which curve is followed. The time spacing between the video frames is defined by the scanning frequency of the video camera.

When the remaining topping up time is currently calculated it may happen that the filling which is once defined as following one of the curves representing connected values of surface distances from the upper edge of the ampoule and topping up time later in the topping up will be defined as following another curve. This may indicate that the liquid flow has changed or that the ampoule geometry differs from the average which forms the basis for the curves.

As a correction of the previewed moment for the completion of the topping up may currently be performed each time a new video frame is scanned, possible variations in flow and ampoule geometry which could influence the preview of the moment when the liquid reaches the upper edge of the ampoule must take place during the filling of the very last part of the neck part of the ampoule in the time from the last scanning during the topping up and to the moment when the topping up is completed, i.e. during a time shorter than the time between two scannings. Consequently the risk for serious changes is negligible.

To enable a last correction during the filling of the neck part it is preferred that the video camera has a scanning frequency allowing it to detect the liquid surface position at least two times during the filling of the neck part.

In the following the invention is described with references to the drawing, wherein

Figure 1 shows schematically a filling station according to the invention .

Figure 2 shows a bundle of curves representing connected values of distances of the liquid surface from the upper edge of the ampoule and remaining topping up times at different specific flows of liquid.

A filling station according to the invention is schematically shown i figure 1 . The liquid which is going to be filled into the ampoules is stored in a tank 1 from which the liquid is supplied through a tubing 3 to a filling needle 4. The flow from the tank 1 through the tubing 3 is on/off controlled by a solenoid valve 2 which allows passage through the tubing or blocks this passage by pinching the tubing dependent on a signal on a line 8. The liquid is driven through the tube either by gravity or by a pressurized gas in the tank 1. As the variation of the level of the liquid in the tank 1 will be infinitesimal during the filling of an ampoule, the flow of liquid through the tubing will be practically uniform during the filling process.

The about 80% prefilling of the ampoule is performed in one or two filling station preceding the station schematically shown i figure 1 which performs a topping up of a partly filled ampoule 5. The topping up is monitored by a video camera 7 from which a video signal is transmitted to a picture processing unit 6 comprising means for currently processing the video signal to detect the position of the surface of the liquid in the ampoule 5, a data storage, and computing means for performing calculations on the basis of the data stored and the data represented in the video signal.

As the geometry of the ampoule is known it is possible to estimate time/level curves for the filling of this ampoule as shown in the diagram in figure 2. The time along the ordinate is the time until the topping up is completed. To the right in the diagram the curves illustrates the relations between the position of the surface of the liquid in the ampoule and the time the remaining topping up will take during the filling of the wide part of the ampoule whereas in the left part the curves illustrates the same relations during the filling of the neck part of the ampoule. As these two parts are cylindric but have different diameters the curves are mainly straight lines whereas the curves representing the passage of the shoulder region are curves reflecting the variation of the ampoule diameter in this part.

When an ampoule arrives to the topping up station the top, the neck part, the shoulders and an upper part of the wide part is monitored by a video camera. The two first frames in which the surface of the liquid in the ampoule is visible may be used to define which curve is followed in figure 2. For each new frame showing the position of the level of the liquid in the ampoule a further correction of the first calculation may be made so that the correct time for the completion of the topping up may be calculated with good accuracy even when the flow of liquid is not quite uniform during the topping up. On the basis of the calculated time for the completion of the topping up a signal is sent via the line 8 to the solenoid valve 2 to make this valve pinch the tubing to stop the flow of liquid through this tubing. The time for the sending of the signal on the line 8 is calculated taking into account the reaction time of the solenoid valve and the fact that some liquid may leave the filling needle after the tubing has been pinched. As the video camera transmits a picture of the ampoule after the topping up has been completed, it is possible to check whether the time admitted for the solenoid valve to react is correct and if necessary to perform a further correction when the following ampoule is topped up.

As the topping up function is not dependent on the level of liquid in the ampoules by the start of the topping up, the demand to the precision of the 80% filling may also be modified and a time/pressure filling may be used even when the pressure varies within reasonable limits. The main demand is that the ampoules by their arrival to the topping up station is sufficiently prefilled to enable a topping up during the time reserved for this purpose.

Claims

1 . Filling station for topping up cylinder ampoules with a liquid supplied through a tubing controlled by a solenoid valve, characterized in that an upper part of the ampoule in the station is monitored by a video camera from which a picture signal is transmitted to a picture processing and calculating unit in which the position of the surface of the liquid in the ampoule, the position of the upper edge of this ampoule and the distance between the surface and the upper edge of the ampoule are currently calculated, and wherein it is currently calculated when the surface of the liquid will reach the upper edge of the ampoule, and a signal is generated which causes a closing of the solenoid valve to stop the flow of liquid to the ampoule at the moment when the liquid is previewed to reach the upper edge of the ampoule.

2. A filling station according to claim 1 , characterized in that data representing a bundle of curves is stored in the calculation unit, each curve representing connected values of surface distances of from the upper edge of the ampoule and topping up time by a specific flow of liquid.

3. A filling station according to claim 2, characterized in that the topping up time is defined by detecting the liquid surface positions in two consecutive video frames with a known time spacing to define which curve is followed.

4. A filling station according to anyone of the preceding claims, characterized in that the video camera has a scanning frequency allowing it to detect the liquid surface position at least two times during the filling of the neck part.