EP0793954A1 - Packaging unit for freeze-dried preparations - Google Patents

Abstract

The assembly consists of two containers or bottles (A, B), one closed by a seal (14) which can be perforated by a droplet dispenser (30) on the other. The first bottle (A) contains a solid product (P), and the second one has a liquid in it which mixes with the solid product to produce a colloid. The first of the two bottles has an elastomer stopper (10) in its neck which has a central channel (12) and lateral apertures which allow gases formed during the colloid production process to escape. The seal (14) which is perforated by the tip of the droplet dispenser (30) is of aluminium coated with a plastic, which can be sealed by ultrasound.

Description

The present invention relates to an improvement to assemblies intended for the extemporaneous preparation of solutions or suspensions of a solid active product, and in particular to an assembly of this type, the closure cap of the bottle containing the active product allows better product efficacy. active, both in quality and quantity.

Such an assembly, the principle of which is described in patent EP-A-0.138.681, consists on the one hand of two hermetic bottles, the first of these bottles being intended to contain said active product generally in the form of dry lyophilized powder , and the second being intended to contain the liquid in which the said product must be dissolved or in suspension at the time of its administration, and on the other hand a connecting piece allowing the communication of these two bottles, in view, firstly, of introducing said liquid into the first bottle then, secondly, of sucking into the second bottle the solution or suspension thus formed.

To this end, the first bottle A is rigid, for example made of glass, and closed by an elastomer stopper covered with a perforable cover, which is inserted into the neck of the bottle and has an axial channel. The second bottle B made of flexible material, is closed by a dropper whose conical and rounded end has a diameter slightly smaller than that of the axial channel of the stopper. To allow the communication of the two bottles, we start by making the connecting piece integral with the first bottle, for example by snap-fastening of the lower part of the connecting piece on the neck of the bottle. Then the bottle B is screwed into the connecting part by means of an external thread of the cylindrical part of the stilligoutte matched with the internal thread of the upper part of the connecting part. During the screwing, the stilligout comes to penetrate the stopper of the rigid bottle, while maintaining the seal between the two bottles. By compressing the second bottle, it causes the passage of the liquid in the first bottle. By shaking the assembly, the suspension or solution is created, then by inverting the assembly and by successive pressures on the second bottle, the said solution or suspension is returned to the second bottle where it is easy to enclose it by placing a stopper on the stilligoutte.

The second bottle, thanks to its dropper whose end is conical and rounded, can then be used for multiple pharmaceutical, cosmetic or other uses without the user running the risk of injury.

As we have just seen, the rigid bottle has a stopper comprising an axial hole which is far preferable to a stopper comprising a slot preformed in a wall of deformable material as is the case of the device described in EP-A-0.138 .681. Indeed, it is on the one hand difficult if not impossible to correctly insert the stilligoutte through the wall of deformable material if its end is not pointed. And, on the other hand, the operation consisting in returning the solution (or suspension) from the rigid bottle into the bottle provided with the dropper becomes technically very difficult since the opening located at the pointed end of the dropper is very restricted in this case.

Until now, the caps used to close the bottles containing the active product have been placed on the latter outside the lyophilization chamber, with the drawback of a return to moisture which is harmful for the unaltered preservation of the active product. .

In addition, another drawback comes from the fact that if the bottle containing the lyophilized product is to be sealed, the lid is fixed to the stopper by bonding with the risk that particles of adhesive migrate into the solution when overturning the vials and alter the solution.

This is why the object of the invention is to provide a packaging assembly of the type with two bottles placed in communication as described above, but having a stopper which does not have the abovementioned drawbacks.

Another object of the invention is to provide a packaging unit of the above type for which the bottles are closed during the lyophilization phase.

Yet another object of the invention is to provide a packaging unit of the above type for which there is no risk of contamination of the active product when the two bottles are placed in communication.

The main object of the invention is therefore a packaging assembly intended for the extemporaneous preparation of suspensions or solutions of a solid active product in a liquid product, the active product having undergone lyophilization and being contained in a bottle A, and the liquid product being contained in a bottle B closed by a dropper, a connecting piece allowing the communication of the two bottles in view, initially passing the liquid from the bottle B into the bottle A containing the solid, then, in a second step, invert the assembly and aspirate the suspension or solution thus formed in the bottle B, the bottle A containing the active product being closed by an elastomer stopper. The assembly is characterized in that the stopper closing the bottle A comprises a central perforation making it possible to put the bottles A and B in communication, several lateral recesses (36, 38, 40 and 42) so that the lyophilization phase of the active product is applied to the bottle A in which the stopper is only partially depressed so that the gases resulting from the lyophilization are evacuated outside the bottle by passing through the lateral recesses, and a cover perforable by the stilligoutte when the bottles are placed in communication by means of the connecting piece, the cover being made of aluminum sealed on the stopper by means of a sealable plastic film.

Another object of the invention is a packaging unit as defined above in which the upper part of the recesses of the plug is placed in communication with the central perforation of the latter so as to be able to suck all of the the suspension or solution formed after placing the two bottles in communication and inverting the assembly.

• la figure 1 représente une coupe du flacon A d'un ensemble de conditionnement antérieur dans lequel la pièce de liaison dispose d'un capuchon,
• la figure 2 représente une coupe du flacon A de l'ensemble de conditionnement selon l'invention dans lequel la pièce de liaison est munie d'un opercule auto-cassant,
• la figure 3 représente une vue partiellement en coupe de l'ensemble de conditionnement selon l'invention lorsque le flacon B a été vissé dans la pièce de liaison pour mettre le flacon A et le flacon B en communication,
• la figure 4 est une coupe du bouchon obturant le flacon A,
• la figure 5 est une vue de face du bouchon obturant le flacon A, et
• la figure 6 est une vue de dessous du bouchon illustré sur la figure 5 montrant la perforation centrale et les évidements latéraux.

The aims, objects and characteristics of the invention will be better defined on reading the following description made with reference to the drawings in which:

• FIG. 1 represents a section of the bottle A of an anterior packaging assembly in which the connecting piece has a cap,
• FIG. 2 represents a section of the bottle A of the packaging unit according to the invention in which the connecting piece is provided with a self-breaking cover,
• FIG. 3 represents a partially sectional view of the packaging assembly according to the invention when the bottle B has been screwed into the connecting piece to put the bottle A and the bottle B in communication,
• FIG. 4 is a section of the stopper closing the bottle A,
• FIG. 5 is a front view of the stopper closing the bottle A, and
• Figure 6 is a bottom view of the cap illustrated in Figure 5 showing the central perforation and the lateral recesses.

Until recently, the glass vial containing the active ingredient P and conditioned after lyophilization was presented as illustrated in FIG. 1.

The bottle designated by the reference A to be distinguished from the other bottle having the reference B, is closed by an elastomeric stopper 10 having a vertical perforation 12 and surmounted by a perforable aluminum cover 14 fixed on the stopper 10. The bottle A is supplied to the customer by being equipped with a connecting piece 16 covering the neck of the bottle A and which will be used to put the bottle A in communication with the bottle B containing the liquid product making it possible to put the active principle P in solution or in suspension.

The connecting piece 16 comprises an upper portion 18 in the form of a socket having an internal thread for screwing the bottle B into it, and a lower portion 20 which is fixed to the bottle by snap-fastening on a shoulder of the neck of the bottle A When supplied to the customer, the connecting piece 16 is capped with a cap 21.

Now, and in order to avoid the danger presented by possible penetration of impurities into the bottle A, it is provided that the top of the upper portion 18 of the connecting piece 16 can be closed by a self-breaking seal 22 forming a single molding piece with the connecting piece as illustrated in FIG. 2. This self-breaking cover 22 can easily be separated from the connecting piece 16 by pushing on an eccentric vertical bar 24 comprising a strut 26 and connected to the connecting piece 16 by a thin wall.

To use the active product P contained in the bottle A, a second bottle B is placed in communication with the bottle A as illustrated in FIG. 3.

The bottle B made of compressible plastic material and containing the solvent, is turned over and screwed into the upper portion 18 of the connecting piece 16 by means of an external thread adapted to the internal thread of the portion 18.

The threaded cylindrical part 28 is extended by a dropper 30, which, when the bottle B is screwed into the connecting piece, punctures the lid 14 of the stopper 10 of the bottle A and opens into the perforation 12, putting in communication the two bottles A and B. Then, by compressing the bottle B, one causes the passage of the liquid solvent in the bottle A. Then by shaking the whole, one creates the solution of active principle. Finally, by inverting the assembly and applying successive pressures on the bottle B, the solution is returned to the bottle B which is thus ready for use.

As previously mentioned, bottle A is packaged by freeze-drying. During this lyophilization process, it is necessary for the liquid contained in the active ingredient A to have evaporated in order to avoid any trace of humidity, which was the case when the capped antibiotic type caps were installed at the outlet of the lyophilizer in the prior art. It is to avoid such a risk that the plug 10 shown in FIGS. 4, 5 and 6 has a particular shape as explained below.

The elastomer stopper 10 comprises a plate 32 which covers the opening of the neck of the bottle A when the stopper is pressed. The plate 32 is covered with a sealed aluminum cover as we will see later. The part 34 intended to be inserted into the neck of the bottle is extended by a portion having a sectional shape illustrated in FIG. 6, that is to say that the elastomer cylinder comprises four identical vertical recesses 36, 38, 40 and 42 , the recess 36 being highlighted in FIG. 5.

On each of the four non-recessed portions separating the recesses, there is a stop 44, 46, 48 or 50. Finally, as mentioned previously, the stopper has a central perforation 12 intended to put the bottles A and B in communication when the stilligoutte perforated the lid 14.

When the glass vials containing the active ingredient are subjected to lyophilization, they are placed in the lyophilizer with the caps already placed in the vials. The plugs are not fully inserted into the necks, but only partially, the stops 44, 46, 48 and 50 resting on the edge of the neck. When the lyophilization takes place, the gases are therefore evacuated from the bottles thanks to the four lateral recesses of each stopper. Then, at the end of freeze drying, and still inside the freeze dryer, the final insertion of the plugs is carried out by exerting a force at the top which allows the solid cylindrical portion 34 to be introduced into the neck.

The stopper closing the bottle A which has just been described with reference to FIGS. 4, 5 and 6, has brought about some problems which have been resolved within the framework of the present invention.

The first problem which has been solved by this invention is due to the configuration of the plug. As we have seen, the lateral recesses 36, 38, 40 and 42 are necessary in the lyophilization phase. However, when the active principle contained in the bottle A is dissolved or suspended by placing it in communication with the bottle B and then inverting the whole, part of the product may remain in these recesses because the passage of the product from one bottle to the other takes place through the central hole 12, the inlet of which is higher than the recesses. This portion of the unused product is not negligible and represents a loss for the customer.

This is why the plug 10 has two horizontal holes 52 (see FIG. 5) and 54 (see FIG. 4) putting the recesses in communication with the central hole 12. Thus, the hole 52 puts the recess 36 and the recess 40 in communication with the central hole while the hole 54 communicates the recess 38 and the recess 42 with the central hole. In this way, when the liquid obtained by dissolving or suspending the active principle of the bottle A passes into the bottle B, almost all of it flows out and the loss due to the recesses becomes negligible.

A second problem related to the fixing of the aluminum cover 14 on the plug 10. Indeed, until now, the generally aluminum cover, is fixed on the plug by gluing. This has two drawbacks. First of all, during sterilization in an autoclave which takes place before the vials are subjected to lyophilization, there is sometimes detachment of the lid by softening of the glue due to the high temperature. Then, when after having established the communication between the two bottles, the assembly is reversed so that the liquid passes back into the bottle B, the product comes into contact with the glue which is located under the seal at the location of the hole central in the cap. It has been established that in some cases there could be migration of glue particles in the preparation and therefore alteration of the properties thereof.

This is why, according to the invention, the cover is fixed by sealing on the stopper. First, a layer of aluminum is superimposed on a thin polyethylene film. Then proceed to the sealing using an instant softening means of the polyethylene layer so as to strongly adhere it to the aluminum during the curing which follows this treatment. Such sealing is preferably carried out by compressing the seal on the stopper and applying ultrasound to the aluminum-polyethylene assembly, but can be achieved by any other means. The plugs thus closed are then sterilized with steam without danger of detachment of the polyethylene layer. In addition, there is no longer any danger of pollution of the solution or suspension of active product by particles of adhesive during the overturning of the bottles.

Claims (5)

Packaging assembly intended for the extemporaneous preparation of suspensions or solutions of a solid active product in a liquid product, the active product having undergone lyophilization and being contained in a bottle A, and the liquid product being contained in a bottle B closed by a dropper (30), a connecting piece (16) allowing the communication of the two bottles in view, firstly passing the liquid from the bottle B into the bottle A containing the solid, then, in a second time, turn the assembly over and aspirate the suspension or solution thus formed in bottle B, said bottle A containing the active product being closed by an elastomer stopper (10);
said assembly being characterized in that said plug comprises: - a central perforation (12) allowing communication between the bottles A and B, - several lateral recesses (36, 38, 40 and 42), so that the lyophilization phase of the active product is applied to the bottle A in which the stopper is only partially inserted so that the gases resulting from the lyophilization are evacuate outside said flask passing through said lateral recesses, and - A cover (14) perforable by said stilligoutte when said bottles are placed in communication by means of said connecting piece, said cover being made of aluminum sealed on said stopper by means of a film of sealable plastic. A packaging assembly according to claim 1, in which the portion of said plug (10) comprising said lateral recesses (36, 38, 40, 42) comprises stops (44, 46, 48, 50) intended to retain said plug partially depressed during of the lyophilization phase. Packaging assembly according to claim 1 or 2, in which the upper part of the recesses (36, 38, 40, 42) of said stopper (10) is placed in communication with said central perforation (12) so as to be able to aspirate into the bottle B all of the suspension or solution formed after placing the two bottles in communication and turning the assembly over . Packaging assembly according to Claim 3, in which said plug (10) has four identical recesses (36, 38, 40, 42) which are symmetrically arranged and the upper part of which is placed in communication with said central perforation (12) by two holes transverse (52, 54) connecting said recesses two by two. Packaging assembly according to one of claims 1 to 4, wherein said seal (14) is sealed on the cap (10) by means of said plastic film sealable by application of ultrasound.

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