IE41595B1

IE41595B1 - Process for the preperation of a closed container containing lyophilized material

Info

Publication number: IE41595B1
Application number: IE173075A
Authority: IE
Original assignee: Behringwerke Ag
Priority date: 1974-08-06
Filing date: 1975-08-05
Publication date: 1980-02-13
Also published as: LU73136A1; GB1520014A; BE832179A; DK355475A; IE41595L; IT1040462B; FR2281276A1; ES439886A1; DE2437788A1; NL7509207A

Abstract

1520014 Lyophilized material BEHRING- WERKE AG 4 Aug 1975 [6 Aug 1974] 32449/75 Heading A2D A process for the preparation of a closed container containing lyophilized material comprises (1) filling the material to be lyophilized into a container, (2) putting a rubber stopper and an over cap loosely on the container, (3) introducing the container with its contents into a lyophilization apparatus, (4) lyophilizing the contents (5) within the lyophilization apparatus and in a single operation pressing the rubber stopper deep into the container, at the same time pressing the over cap onto the same and (6) removing the container closed under sterile conditions from the lyophilization apparatus. An over cap suitable for use in the above process is described in British Patent Application 32450/75 (Division B8).

Description

The present invention provides a process for the preparation of a closed container containing lyophilized material.

In general, a pharmaceutical preparation or 5 reagent which is to be lyophilized is filled into a container, for example, a bottle, in the form of an aqueous solution. Then, a rubber stopper of a special form is inserted loosely to about half of its length into the container. The container thus prepared is then placed into the lyophilization apparatus. After lyophilization, but still within the apparatus, the rubber stopper is pressed hydraulically into the container. The container is then removed from the apparatus and is transported to a flanging machine which places an aluminium cap onto it under sterile conditions and edges it up or down. This last step is very time-consuming, and moreover, the space between the rubber stopper and the flanged cap can be kept sterile only with great difficulty or even not at all. When the solution is taken 2o out for injection into a subject, any bacteria and fungi which are present between the rubber stopper and the flanged cap can be carried down into the bottle by the injection syringe, thus infecting the injection solution. In the subject to which the injection is administered these organisms may cause conditions that are dangerous to life.

The present invention provides a process for the preparation of a closed container containing lyophilized material, which comprises: 1) filling the material to be lyophilized into a container, 2) putting a rubber stopper and an overcap loosely on the container, 3) introducing the container with its contents Into a lyophilization apparatus, 4) lyophilizing the contents, ) within the lyophilization apparatus and in a single operation, pressing the rubber stopper deep into the container, at the same time pressing the over-cap onto the container, and 6) removing the container closed under sterile conditions from the lyophilization apparatus.

As the over-cap, there is preferably used the plastics cap described and claimed in Patent Specification No. 4 / $Ίb which consists of a plate member, optionally provided with a downwardly extending annular flange, the said plate member being adapted to fit over the upper part of a stopper that in use seals the neck of a container on which the cap is used, and an annular member the inner wall of which is provided with a circumferential groove adapted to engage in a snap-fit manner an external circumferential bead or lip on the neck of the said container, the plate member and the annular member being connected by 3 or more, preferably from 4 to 10, tearable bridging members.

This over-cap is mainly suitable for the packaging of reactants. By a slightly twisting movement of the plastics cap or by pressure on the plate by the thumb, the bridging elements are torn, the upper part can be taken off, and the rubber stopper can be removed.

For injection preparations, the plate of the upper part of the over-cap is preferably provided with a pull-off flap. The rubber stopper is thus made accessible for the needle of the injection syringe, and the contents of the bottle can be dissolved and taken out under sterile conditions. If a pull-off flap is provided, the bridging elements between the top and the bottom parts of the plastic cap are not reguired.

The process of the invention for preparing a container that has been closed under sterile conditions may be effected as follows :After the container has been filled with the solution or suspension to be lyophilized, the rubber stopper is inserted loosely and the over-cap is placed over the rubber stopper by the same machine. The solution is then lyophilized in the usual manner. After the lyophilization process has been completed, the rubber stopper is pressed into the container, and the over-cap is, at the same time, pressed onto the container. In this manner, the transportation of the container to a flanging machine, as well as the placing and flanging of an aluminium cap is no longer necessary.

During the pressing process in the lyophilization apparatus using a snap-fit cap, a groove provided in the annular member of the closing cap engages a lip or bead at the neck of the container, thereby securing the rubber stopper. Caps having this form of annular member are pilfer-proof. If bridging elements are present, these must be torn to gain access to the stopper, and if a pull-off flap is removed, an opening in the form of the flap remains in the plate of the upper part of the plastic cap. In either case, any tampering can be detected without difficulty. / A special advantage of the process of the invention is the fact that the possibility of infection with germs is minimised, The withdrawal of the lyophilized material, too, is facilitated, as the removal of the aluminium flanged cap used previously is difficult and may cause injuries. In contradistinction thereto, the plate of an over-cap having bridging elements can be easily lifted with slight pressure of the thumb, and a pull-off flap can be torn off easily and without risk of injury.

Claims

1. CLAIMS:1. A process for the preparation of a closed container containing lyophilized material, which comprises (1) filling the material to be lyophilized into a 5 container, (2) putting a rubber stopper and an over-cap loosely on the container, (3) introducing the container with its contents into a lyophilization apparatus, I (4) lyophilizing the contents, (5) within the lyophilization apparatus and in a single operation, pressing the rubber stopper deep into the container, at the same time pressing the over-cap onto the same, and (6) removing the container closed under sterile conditions from the lyophilization apparatus.

2. A process as claimed in claim 1, in which the over-cap consists of a plate member, optionally provided with a downwardly extending annular flange, the said plate member being 20 adapted to fit over the upper part of a stopper that in use seals the neck of a container on which the cap is used, and an annular member the inner wall of which is provided with a circumferential groove adapted to engage in a snap-fit manner an external circumferential bead or lip on 25 the neck of the said container, the plate member and the annular member being connected by 3 or more tearable bridging members.

3. A process as claimed in claim 2, wherein the plate member is provided with a pull-off flap.