ITMI20110789A1 - GROUP FOR SEALING BOTTLES CONTAINING INJECTABLE STERILE DRUGS OR SIMILAR SUBSTANCES, SUITABLE FOR USE IN PRODUCTION LINES OF HIGH-SPEED BOTTLES, RESPECTIVE SEALING CAP, AND CORRESPONDING SEALED BOTTLE - Google Patents

Description

â € œ GROUP FOR THE SEALING OF BOTTLES CONTAINING INJECTABLE STERILE DRUGS OR SIMILAR SUBSTANCES, SUITABLE FOR USE IN HIGH SPEED BOTTLES PRODUCTION LINES, RESPECTIVE SEALING CAP, AND CORRESPONDING BOTTLE

Field of invention

The present invention generally refers to the sector of bottles containing drugs or similar substances and their packaging, and more particularly it refers to a device or group for sealing vials or similar containers containing sterile drugs, of the injectable or non-injectable type. , suitable for use in production and packaging lines of bottles characterized by high speed and production capacity.

The present invention also relates to a new sealing cap suitable to be advantageously used in lines for the automatic packaging of sealed bottles containing sterile injectable drugs, a new process for the production of sealed bottles containing an injectable sterile drug, as well as an innovative line for the production and high-speed packaging of sealed vials containing a sterile injectable drug.

Background of the invention and state of the art

Numerous systems, devices and processes are known in the art for sealing bottles containing drugs or powders or liquids, sterile, injectable, or similar substances, prepared in various ways.

In particular, in the event that the drug contained in the bottle is a lyophilized drug, the sealed bottles are produced in special packaging lines, preliminarily filling each bottle to be sealed with a pharmacological solution in a filling station.

The bottles are then introduced inside a freeze-drying machine which determines the sublimation of the liquid phase of the solution, after which the bottles are closed with a rubber stopper, and finally sealed with an aluminum ring.

These sealed and packaged bottles, containing the lyophilized drug, are used by removing from the respective sealing system a protective cap, for example of the `` flip off '' type, in order to reveal an area of the rubber stopper intended to be perforated through the € ™ needle of a syringe.

Then the user injects into the bottle, through the syringe, a liquid, which is mixed with the lyophilized drug contained in the bottle, so as to prepare a pharmacological solution intended to be injected.

Currently, various systems and devices for closing and sealing vials containing sterile drugs, injectable or not, are available and industrially applied, more or less on a large scale, and for example among these known systems the system known with the commercial acronym LYOSEAL is mentioned.

These sealing systems, currently available on the market, are however not exempt from some drawbacks and disadvantages, which would therefore be appropriate and desirable to remedy, and which constitute precisely the starting point of the present invention.

In particular, in relation to these products, although widely used, the Applicant has observed the following drawbacks, which occur above all in the assembly, packaging and sealing step of these known bottles for sterile injectable drugs.

For example, a first drawback of the LYOSEAL sealing system derives from the fact that it provides a first production phase, in which a rubber stopper is placed on the bottle, and a subsequent phase, in which a sealing unit, in turn composed by an intermediate ring and a locking ring, it is placed on the cap itself.

In fact, this assembly in distinct and successive phases of the rubber stopper and of the sealing unit entails an extension of the production times of the bottles.

A second drawback of the LYOSEAL bottle sealing system arises from the fact that the rubber stopper and the sealing assembly formed by the intermediate ring and the locking ring are not held together in a stable and secure way, while the sealing assembly, pre-assembled, it is handled in the packaging and sealing line of the bottles, so this sealing group tends to be unstable.

It follows that the pre-assembled group, at least under certain critical conditions, can be divided into the pieces of which it is composed, and for example the locking ring nut and the intermediate ring can be detached from the rubber cap, so as to causing anomalies and temporary interruptions in the bottle packaging line, and therefore negatively affect the efficiency and productivity of this packaging line.

Another possible and potential drawback, still observed by the Applicant, of the LYOSEAL sealing system, depends on the material of which the top cover is made, that is the external locking ring nut which receives the external pressure directed to press and completely insert the sealing cap. rubber in the mouth of the bottle in order to seal it.

In fact, this locking ring nut is usually made of plastic material, and therefore tends to easily deform, with the risk of a consequent reduction over time in its ability to fix and stably lock the other two pieces of the sealing group, that is the middle ring and the rubber stopper, after the bottle has been sealed.

Yet another possible drawback can be seen in the fact that the intermediate ring, of the sealing group of the LYOSEAL system, has in the non-deformed configuration, in correspondence with the tip area of the respective flexible tabs, an external dimension, i.e. an external diameter which It is larger than the diameter of the bottle to be sealed.

For example, in the case of the standard called 2R, i.e. bottles with an external diameter of 16 mm, the intermediate ring has, at the tip of the respective tabs when they are still in the initial inclined configuration before being closed in the seat at undercut formed around the mouth of the bottle, an external diameter of 16.8 mm, therefore greater than the diameter of the bottle.

In fact, these sealing groups, which as mentioned above are pre-assembled and each resting on the rubber stopper, which in turn is already partially inserted in the mouth of the bottle, along the relative packaging line, before being definitively pressed onto the bottle containing the lyophilized drug. , or more generally a drug or a powder prepared in any way, so as to seal the bottle, inevitably tend to come into contact and collide with each other with the tabs of the respective intermediate rings, while the bottles are moved in contact with each other and conveyed along the production line, precisely because of the greater diameter that these tabs have as a whole in the tip area compared to that of the bottles to be sealed.

It follows that, due to these contacts and impacts, the sealing groups can tilt and therefore assume an incorrect position, in particular while they are moved along the modern high-speed automatic packaging lines of the bottles, automatic lines that can arrive to manage even 16,000 bottles in an hour, so as to create problems, possible anomalies and interruptions during the handling of the bottles, and therefore negatively affect the productivity of these packaging lines.

Another limit that can be found in the LYOSEAL sealing system is in its specificity which in fact makes it applicable only to seal vials containing a lyophilized drug, and limits its application in a wider context, for example to seal vials containing drugs or powders prepared any way.

Furthermore, regardless of the specific drawbacks, such as those observed by the Applicant and mentioned above and which should be remedied, in the LYOSEAL system and in other products or sealing systems currently available on the market, it is necessary to consider how this sector of packaging and sealing of bottles containing sterile injectable drugs is extremely delicate and sensitive to always welcoming new innovations and improvements, aimed both at increasing the efficiency of the packaging lines of these sealed bottles for injectable sterile drugs, and also at guaranteeing greater safety and product quality final, i.e. the sealed bottle containing the sterile injectable drug.

Summary of the invention

Therefore, a first object of the present invention is to realize a group for sealing vials containing sterile injectable drugs, for example but not exclusively lyophilized drugs, therefore also powders, liquids, and / or substances and / or drugs prepared in any way. , which can be assembled and applied quickly, safely and reliably, and with a limited number of operations, in the packaging and sealing lines of these bottles, so as to significantly increase the efficiency and productivity of these bottles. packaging lines and therefore also substantially reduce the production and packaging costs of sealed bottles.

A second object of the present invention, more particular but still connected to the first, is to introduce specific improvements and improvements which allow to completely eliminate the various drawbacks, as observed by the Applicant and previously mentioned, which are present in the known systems and currently in use, for the sealing of vials containing sterile injectable drugs, and in particular those found in the packaging phase of these sealed vials, in order to make an effective leap towards greater safety, efficiency and quality in packaging and production of these bottles for sterile injectable liquids.

Another object of the present invention is to go beyond and overcome the typical application limits of known bottle sealing systems, and therefore to develop a very versatile sealing unit which can be advantageously used to seal bottles containing a wide range of drugs and preparations, both in solid or powder form, and in liquid form.

A further purpose is also to propose a new sealing cap that can be used with tangible benefits in the automatic packaging and production lines of sealed bottles for injectable sterile fluids, and in particular to avoid problems, interruptions and other possible drawbacks, connected to the use and handling of the sealing cap, which can negatively affect the efficiency and functionality of these automatic packaging and production lines.

Another object of the present invention is to propose a process, for the production of sealed bottles containing a sterile injectable drug, which innovates and is characterized by greater efficiency compared to known processes, as well as to propose an automatic line for packaging and production of these sealed bottles that implements this innovative process.

The aforementioned purposes can be considered fully achieved by the sealing unit for vials containing sterile injectable drugs or similar substances, having the characteristics defined by independent claim 1, by a respective sealing cap having the characteristics defined by independent claim 7, by a corresponding bottle sealed having the characteristics defined by dependent claim 10, and finally by a process for the production of sealed bottles and by a production and sealing line that implements this process having the characteristics defined by claims 11 and 12 respectively.

Particular embodiments of the present invention are further defined by the other dependent claims.

Advantages of the new sealing assembly and the bottle sealed by this sealing assembly

Multiple and relevant are the advantages, as listed below, purely by way of example, and in part already implicitly previously announced, which are associated with the new sealing group for vials containing sterile injectable drugs or similar substances, proposed by the present invention, and that distinguish it from the systems and solutions currently in use.

- Greater efficiency and productivity of the automatic bottle production line, with a significant reduction in the time needed to seal them.

- Great versatility, that is the possibility of using the sealing unit in lines for the production and packaging of sealed bottles containing a wide variety of drugs, freeze-dried or not, in liquid or powder form, prepared in various ways.

- Greater precision and efficiency in the application phase of the sealing group elements, since the sealing group is applied, already pre-assembled in its various elements and in a single operation, on the bottle to be sealed.

- High stability of the bottle sealing over time, thanks to the use of metal materials, such as aluminum, to make the parts of the sealing system, which are able to tolerate the rapid excursion or â € œshockâ € without problems temperature to which the bottle is subjected during the lyophilization process.

- Greater strength of the bottle sealing system.

- Reduced dimensions of the sealing system compared to those known already in use on the market.

- Applicability to seal bottles of different sizes and characteristics, in compliance with the standards on the market.

Brief description of the drawings

These and other objects, characteristics and advantages of the present invention will become clear and evident from the following description of a preferred embodiment thereof, given by way of non-limiting example, with reference to the attached drawings, in which:

Fig. 1 is a photographic schematic view of a sealing unit, according to the present invention, for bottles containing injectable steric drugs or similar substances, broken down into the various pieces of which it is constituted;

Fig. 2 is a photographic view of a bottle for injectable sterile drugs, packaged and sealed by means of the sealing unit of Fig. 1;

Figs. 3A is a normal bottom view, on an enlarged scale, of a new sealing plug included in the sealing system of the invention of Fig. 1;

Fig. 3B is a section view along the line IIIB-IIIB of Fig. 3A; Fig. 3C is a top view of the sealing cap of Fig. 3A;

Fig. 4 is a schematic view, partially in section, of an intermediate basket included in the sealing assembly of Fig. 1;

Fig. 4A is an enlarged scale view of some details, indicated by a dotted and dotted circle, of the basket of Fig. 4;

Fig. 5 is a schematic sectional view of a locking ring included in the sealing assembly of Fig. 1;

Fig. 6 represents in schematic form the various steps for mass-packing, in an automatic packaging line, a bottle containing a sterile injectable drug, sealed with the sealing unit of the invention;

Fig. 7 is a schematic sectional view representing the sealing group of the invention in a pre-assembled configuration, in which the sealing group is preliminarily prepared and assembled on the respective bottle, before being pressed on this bottle. ™ last to seal it permanently;

Fig. 8 is a schematic sectional view which represents the sealing unit of Fig. 7 in an intermediate position during application on the respective bottle;

Fig. 9 is a sectional view, along a longitudinal plane, of the sealing assembly of Figs. 7 and 8, once applied and integrated into the respective bottle, so as to seal it definitively;

Fig. 9A shows an area of the section of Fig. 9 on an enlarged scale; Figs. 10 A and 10B show a protective cover while it is removed from the sealing unit of Fig. 9, in the use of the bottle sealed by it; And

Fig. 10C shows the area of the sealing unit after removing the protective cover of Figs. 10A and 10B; And

Fig. 11 shows a variant of the sealing unit of the invention. Description of a preferred embodiment of the sealing assembly of the invention

With reference to the drawings and in particular to Figs. 1 and 2, a sealing assembly, according to the invention, suitable for sealing bottles containing sterile injectable drugs or similar substances, is indicated as a whole with 10, while a corresponding bottle, containing a sterile injectable drug F or a similar substance and sealed by such a sealing assembly 10, is indicated as a whole with 20.

The bottles 20 sealed with the sealing assembly 10 of the invention conform to unified norms and standards, in particular as regards the dimensions of both the external diameter D of the respective containment body or container 20a, of substantially cylindrical shape, containing for precisely the injectable sterile drug F, and both of the mouth 20b, of this containment body 20a, intended to be sealed during the packaging of the bottle 20.

For example, these bottles 20, if they conform to the 2R standard, have an external diameter D of the respective containment body 20a equal to 16 mm.

In detail, the sealing unit 10 of the invention essentially consists of the following three pieces:

- a sealing cap 11, also called simply a cap, able to be inserted and to seal the opening or mouth 20b formed by the containment body 20a of the bottle 20;

- an intermediate basket 12, able to house and cooperate with the cap 11; And

- a locking ring 14, suitable for housing and cooperating with the intermediate basket 12, in order to stably block the various parts of the sealing assembly 10, once the bottle 20 has been sealed.

The mouth 20b, intended to be closed and sealed by means of the sealing cap 11, is formed in an upper portion 20c, in the shape of a neck and therefore also called simply neck, of the containment body 20a of the bottle 20, and is delimited by a circular edge 20d, projecting externally, such as to form a circular undercut seat 20e in the area of the neck 20c.

Sealing cap

With reference to Figs. 3A-3C, the sealing plug 11, an essential part of the sealing assembly 10 of the invention, will now be described in detail.

The sealing cap 11 is made of a soft material suitable for being pierced by the needle of a syringe, for example rubber or a similar material, and has a first upper portion, or head, 11a, cylindrical, of larger diameter; and a second lower portion, or stem, 11b, cylindrical, of reduced diameter, in which the stem 11b has a slot 11c, having the function of allowing the evacuation of the vapors during a lyophilization phase of the injectable sterile drug F contained in the bottle 20, as better described later on.

The head 11a, having a larger diameter, of the sealing cap 11 also forms, along its external cylindrical surface, a protuberance 11d, with a circumferential development, able to cooperate with a corresponding recess, described later on, formed in the intermediate basket 12.

Furthermore, the head 11a has on its upper surface, opposite the shank 11b, a series of protruding shapes including in particular a continuous circular ring protrusion, indicated with 11f, in the area of the sealing cap 11 intended to be pierced by a syringe, in the € ™ use of the bottle 20.

The shank 11b of the sealing cap 11 in turn has along its external cylindrical surface, on the sides of the slot 11c, some small protruding areas or buttons, indicated with 11e, six in number as shown in Fig. 3A, which are suitably and uniformly distributed in a circumferential direction on the outer cylindrical surface of the shank 11b.

These projections 11e have in particular the function of keeping the sealing cap 11, and with it the whole sealing assembly 10, in a stable position and in axis with the mouth 20b of the containment body 20a, during the packaging of the sealed bottle 20. , as better described below.

With reference to Figs. 3A-3C, some preferred values of the dimensions that define and qualify the sealing cap 11, included in the sealing group 10 of the invention, are indicated below, in case it is intended to seal bottles conforming to the 2R standard, i.e. with external diameter D equal to 16 mm.

A [mm] B [mm] E [mm] M [mm] G [mm] H [mm] I [mm] K [mm] L [mm]

12.7 2 1 0.61 4.25 0.23 1.20 6.75 3.5

<J [mm] R [mm]> Φ [mm] Φ1 [mm] Φ2 [mm] Φ3 [mm] Φ4 [mm] Φ5 [mm]

0.2 0.45 13.1 12.2 7.5 6.5 3 3.5

Î ± Î ̧1 Î ̧2

10 ° 20 ° 20 °

Intermediate basket

With reference to Figs. 4 and 4A, the intermediate basket 12 will now be described in detail.

The intermediate basket 12 is made of plastic material and internally defines an internal cylindrical cavity 12a, suitable for receiving and housing the head 11a of the sealing cap 11, and in particular consists of:

- a hollow cylindrical body, in turn constituted by a flat wall or base 12b, and by a cylindrical tubular body 12c which extends longitudinally, along the axis of the intermediate basket 12, from the base 12b; and by - a crown, generally indicated by 13, which in turn is formed by a plurality or array of petals 13a, flexible, which are arranged around the axis of the intermediate basket 12 and extend from the cylindrical tubular body 12c along the outer surface of the basket 12.

The hollow cylindrical body 12c defines, along its internal surface facing the cavity 12a and adjacent to the base 12b, a recess 12d, with a circumferential development, suitable for receiving and housing the circumferential projection 11d formed on the head or cylindrical portion 11a, of diameter greater than the sealing plug 11.

A hole 12e is formed in the center of the base 12b to allow the passage of a syringe, during the use of the bottle 20, as better described later on.

Each petal 13a of the crown 13 has at the tip a portion, indicated by 13b, with a larger section than that of the stem of the petal 13a, in which this portion 13b forms a tooth 13c, facing the internal cavity 12a of the intermediate basket 12.

As clearly visible in Fig. 4a, the tip tooth 13c of each petal 13a has a rounded and inclined profile 13câ € ™, in order to avoid jamming and therefore favor the correct assembly of the intermediate basket 12 on the edge 20d of the mouth 20b , during the application of the sealing assembly 10 on the containment body 20a of the bottle 20 to seal it, as described in detail hereinafter.

Profile 13câ € ™ has a degree of inclination that can vary according to the size of the mouth of the bottle used, and for example it can be defined by an angle β equal to 45 ° ± 20 ° with respect to a plane perpendicular to the longitudinal axis of petal 13a.

Furthermore, the various petals 13a of the crown 13 each form, in the area of attachment to the cylindrical tubular body 12c, a first recess 13d, facing the outside of the basket 12, and in the tip area, adjacent to the respective increased portion 13b, a second recess 13e, also facing the outside of the basket 12, in which these recesses 13d and 13e of the petals 13a are arranged mutually aligned so as to define a first and a second recess, with a circumferential development, respectively, indicated with 13 'and 13', which extend along a circumference on the outer surface of the crown 13.

The intermediate basket 12 has an initial undeformed or assembly configuration shown in Fig. 4 and indicated with C, in which the petals 13a of the crown 13 are slightly inclined towards the outside of the intermediate basket 12.

In particular, in this initial undeformed configuration C, the tips of the petals 13a of the crown 13, inclined towards the outside, define a circumference with a diameter D1.

Starting from this initial deformed configuration, the crown 13 is expected to assume, at the end of the application of the sealing group 10 to seal the bottle 20, a final configuration Câ € ™ â € ™ represented in Fig. 9, in which the petals 13a are arranged parallel to the axis of the basket 12, as better described later on.

Locking ring

With reference to Fig. 5, the locking ring 14 is constituted by an upper cover 14b, and by a cylindrical hollow body 14c, connected to each other, in which the cylindrical hollow body 14c has a cylindrical internal cavity 14a, suitable for housing the base 12b and the cylindrical tubular body 12c of the intermediate basket 12, and is in turn constituted by a flat base 14câ € ™, which is arranged adjacent to the lid 14b, and by a tubular part 14câ € ™ â € ™ which extends longitudinally from the flat base 14câ € ™.

The cover 14b of this locking ring 14 is made of plastic material, and is fixed on the flat base 14câ € ™ of the cylindrical hollow body 14c by means of a central protuberance 14bâ € ™ of the cover 14b which is inserted in a hole formed on the flat base 14câ € ™ of the cylindrical hollow body 14c and subsequently riveted.

This lid 14b, made of plastic material, is of the type commonly indicated with the English terminology â € œflip offâ €, that is, it is of the type able to be removed manually, in the use of the sealed bottle, from the tubular body 14c, in order to uncovering the area of the sealing cap 11 intended to be pierced by a syringe, as better described below.

The cylindrical hollow body 14c of the locking ring 14 is preferably made by drawing a thin sheet of metal material, in particular aluminum, and has along its internal surface, facing the cavity 14a of the locking ring 14, and adjacent to the edge of the tubular part 14câ € ™ â € ™, a protuberance or projection 14d, with a circumferential development, the function of which will be better explained later in the description, which is again obtained by drawing the sheet of metallic material constituting the cylindrical hollow body 14c.

Process of packaging a sealed bottle of the invention, containing a sterile injectable drug

The characteristics of the sealing unit 10, according to the present invention, for sealing vials containing sterile injectable drugs, will be further clarified by the following description, made with reference to Fig. 6, of the packaging steps, in an automatic packaging line indicated generally with LCA, of a bottle 20, containing a sterile injectable drug F, sealed with this innovative sealing assembly.

In particular, the packaging process of the bottle 20 comprises a first step (f-1), in which the containment body or container 20a of the bottle 20 is filled, in a corresponding filling station (a), with a drug FL , in liquid form, through a small tube T.

For example, the container 20a is filled with 1 cc of drug FL, which, in the case of a bottle conforming to the 2R standard with a diameter of 16 mm, means filling the container 20a with liquid up to a level of approximately 7-8 mm. from its bottom.

Subsequently, the containment body 20a, once filled with the liquid drug FL, is transferred via a conveying line, schematized in Fig. 6 with arrows LC, to a subsequent assembly station (b), where the containment body 20a receives the sealing assembly 10, during a corresponding assembly step (f-2).

The sealing unit 10, which is mounted on the containment body 20a in this assembly station (b), in turn has already been suitably prepared, with the respective three pieces, i.e. the sealing cap 11, the intermediate basket 12 and the locking ring 14, in a pre-assembled configuration indicated by CP and shown in detail in Fig. 7.

The phases through which the sealing unit 10 is set up in this pre-assembled configuration CP are the following.

In a first preliminary phase (fp-1), with the intermediate basket 12 suitably arranged so as to present the crown 13 oriented with the tip of the petals 13a upwards, the sealing cap 11 is inserted inside of the cavity 12a of the intermediate basket 12, so as to house the circumferential projection 11d, formed in the head 11a of the sealing cap 11, in the corresponding seat 12d formed in the cavity 12a of the intermediate basket 12.

In this way, the sealing cap 11 is stably retained inside the cavity 12a of the intermediate basket 12.

Note how the insertion of the sealing cap 11 into the internal cavity 12a of the intermediate basket 12 is favored and facilitated by the fact that the ends of the petals 13a, of the crown 13, define towards the inside of the cavity 12a a diameter which It is larger, albeit slightly, than the diameter Φ of the circumferential projection 11d formed on the head 11a of the sealing plug 11.

Then, after having overturned in a second preliminary phase (fp-2) the group formed by the sealing cap 11 and the intermediate basket 12, the locking ring 14 is mounted on the intermediate basket 12, in a subsequent preliminary phase (fp- 3), so that the circumferential protuberance 14d, protruding inside the cylindrical hollow body 14c, of the locking ring 14 engages the circumferential recess 13â € ™ formed on the external surface of the basket 12, in the area adjacent to the base of the 13a petals of the crown 13.

In this way, the sealing assembly 10 assumes the preliminary pre-assembled configuration CP, as shown in Fig. 7.

The assembly operation of the locking ring 14 on the intermediate basket 12 and the consequent engagement of the protuberance 14d with the circumferential recess 13â € ™ causes a slight bending or closing, towards the inside of the intermediate basket 12, of the petals 13a, which in this way define with their tips a circumference of diameter D1â € ™, corresponding to a deformed configuration Câ € ™ of the crown 13, as shown in Fig. 7, in which this diameter D1â € ™ is a little bit Less than the diameter D1 corresponding to the initial undeformed configuration C of the petals 13a.

In particular, in the case of the aforementioned standard 2R of the bottles, the petals 13a of the corolla 13 are configured in such a way as to define with their tips, in the undeformed configuration C, a diameter D1 equal to about 17 mm, and to flex, towards the Internal, as indicated by arrows fâ € ™ in Figs. 4 and 7, following the assembly of the locking ring 14 on the intermediate basket 12, so as to define, in the deformed configuration Câ € ™, a circumference having a diameter D1â € ™ of approximately 15.5Ã · 15.75 mm, however smaller of the standard diameter D, equal to 16 mm, of the containment body 20a of the bottle to be sealed, or with D1â € ™ <D.

Now, returning to the assembly of the sealing assembly 10, in the pre-assembled configuration CP, on the mouth 20b of the containment body 20a, this assembly is carried out by inserting the stem 11b of the sealing cap 11 into the mouth 20b until the protrusions 11e, formed on the external surface of said stem 11b, they abut and stop against the flat surface 20dâ € ™ of the edge 20d which delimits and on which the mouth 20b faces externally.

Therefore, in the assembly station (b), the sealing cap 11 is inserted only for a certain length in the mouth 20b, so as to leave a part of the slot 11c uncovered.

In this phase, the fact that the projections 11e are distributed uniformly along the entire circumference, and not only over a small portion thereof, of the cylindrical surface of the shank 11b, ensures correct positioning in the vertical direction, parallel to the Axis of the mouth 20b, of the sealing cap 11 and therefore also of the sealing assembly 10 which, in the pre-assembled configuration CP shown in Fig. 7, is mounted on the containment body 20a.

Furthermore, these projections 11e ensure that the sealing cap 10, and with it the sealing assembly 10, are held stably in the correct axial position in which they were inserted in the mouth 20b, and for example do not tilt during the handling of the bottles. along the respective LCA automatic packaging line.

Then, during a step (f-3), the containment bodies 20a, each with a sealing assembly 10 partially inserted in the mouth 20b, are conveyed to a freeze-drying chamber CL, again schematized in Fig. 6.

It should be noted that, in this phase, as well as in the following ones, the various bottles are moved and conveyed one in a row to the other along the LCA conveying line in a regular manner and without the risk that the sealing groups 10, - assembled, mounted on each of them, they come into contact with each other, so as to cause anomalies in the regular operation of the bottle packaging line.

In fact, as already pointed out above, the petals 13a of the crown 13 of the intermediate basket 12 define at the tip, in the preassembled configuration CP of the sealing unit 10, a circumference, with a diameter D1â € ™, which is smaller than the standard diameter D of the body containment 20a of the bottle to be sealed, or with D1â € ™ <D, so that the sealing groups 10, mounted on the containers 20a which are moved and conveyed one in a row and in contact with each other along the LC conveyance line, are separated by a space S, as also shown with dashed and dotted lines in Fig. 7.

In the lyophilization chamber CL, during a process step (f-4), the bottles are subjected to a lyophilization process with known characteristics.

In particular, the bottles are subjected to a rapid excursion or thermal `` shock '' that can go from -60 to 40 ° C, and which first determines the solidification of the liquid phase contained in the FL drug, and then its sublimation from the solid phase. gas phase, with the consequent formation inside the container 20a of a porous compound, also called in the jargon with English terminology â € œcakeâ €, consisting of the lyophilized drug F.

In this process phase or lyophilization (f-4), the vapors V which are produced by the effect of the sublimation from the solid phase to the gaseous phase are vented outside the container 20 through the slot 11c, formed in the sealing cap 11, as indicated by arrows schematizing these vapors V in Figs. 6 and 7.

It should be noted that, in this freeze-drying phase, the locking ring, being at least partially made of aluminum, is able to optimally support the thermal `` shock '' of the sublimation process, without deforming and therefore without inconveniences that they could negatively affect the quality and durability of the seal.

On the contrary, the sealing systems currently applied are often entirely made with materials, such as plastics and the like, which poorly tolerate the thermal shock of the freeze-drying process, and in particular due to this shock they tend to deform and lose their mechanical characteristics. and resistance, with the risk of possible inconveniences in terms of the safety and tightness of the bottle seal over time.

Then, once the lyophilization step is completed, the containers 20a, containing the lyophilized drug F, are hermetically closed and sealed inside the lyophilization chamber CL.

In particular, this sealing phase is carried out in a corresponding sealing station (c) by applying a pressure P from above on the locking ring 14 of each sealing group 10, so as to determine the complete insertion of the sealing cap 11 in the mouth 20b of the container 20a.

More in detail, the pressure P, applied from above on the locking ring nut 14, determines, during a first phase (f-5), an axial downward advancement of the sealing assembly 10 for a portion X1, as indicated by an arrow f1 in Fig. 8.

In this first insertion phase (f-5), the sealing unit 10 maintains its pre-assembled configuration CP, with the locking ring 14 which continues to engage the circumferential recess 13â € ™ â € ™, up to that the head 11a of the sealing cap 11 abuts against the surface 20d 'of the upper edge 20d of the container 20a.

Therefore, when the head 11a of the sealing cap 11 comes into contact and abuts against the surface 20dâ € ™ of the edge 20d, the pressure P determines the disengagement of the protuberance 14d from the circumferential recess 13â € ™, whereby, with the sealing cap 11 and the intermediate basket 12 stopped against the edge 20d, the locking ring nut 14 after having disengaged from the recess 13 'slides relative to the intermediate basket 12 for a further axial length X2, during a second phase (f- 6) and as indicated in Fig. 9, again in the direction of the arrow f1, until the circumferential hollow 13â € ™ â € ™ formed in the tip area of the petals 13a of the corolla 13 of the intermediate basket 12 is engaged with the protuberance 14d .

In this second phase (f-6), the locking ring 14, advancing axially along the portion X2, engages with the respective cylindrical hollow body 14c, made of aluminum, the petals 13a of the corolla 13 so as to flex them inwards , as indicated by arrows f2 in Fig. 9, and therefore close them stably and block them against the undercut seat 20e formed by the edge 20d of the mouth 20b.

Therefore, the teeth 13c of the petals 13a of the corolla 13 close and engage the undercut seat 20e, so as to stably block the sealing cap 11, now completely inserted, in the mouth 20b of the container 20a.

Note how the tip portion 13b of each petal 13a is suitably configured so as not to protrude outwards from the cylindrical surface of the hollow body 14c of the locking ring 14, in the final configuration assumed by the crown 13, or with the respective petals 13a engaged in the undercut seat 20e to lock the sealing cap 11.

Fig. 9 shows the sealing unit 10 once completely assembled on the container 20a, with the sealing cap 11 completely inserted and locked in the mouth 20b, and the intermediate basket 12 in a final configuration Câ € ™ â € ™, in which the petals 13a are closed on the undercut seat 20e and arranged parallel to the axis of the mouth 20b.

In this final assembled configuration of the sealing assembly 10, as shown in Fig. 9A, the central protuberance 14bâ € ™ formed by the cover 14b of the locking ring 14 cooperates in contact with the continuous circular projection 11f formed on the upper surface of the head 11a of the sealing cap 11, so as to protect and keep sterile over time the area of the sealing cap 11 intended to be pierced by a syringe.

Then in a further phase (f-7) the various sealed bottles, indicated with 20-1, 20-2, 20-3, etc., arranged in a row one to the other, are evacuated from the CL freeze-drying chamber to be subjected to other operations, such as inspection, labeling, and final packaging.

In actual use of the sealed bottles 20, the user removes manually, as shown with an arrow f3 in Figs. 10A - 10B, the plastic cover 14b from the locking ring 14, so as to cause the breakage of a series of jumpers 14e which connect the flat base 14câ € ™ of the circular hollow body 14c, in aluminum, of the locking ring 14, to the central protuberance 14bâ € ™ of the lid 14b.

In this way, as shown in Fig. 10C, the area of the sealing cap 11 corresponding to the circular projection 11f is discovered, so that the user can pierce this area with a syringe SI.

It is therefore clear, from what has been described, that the present invention fully achieves the aims it had set itself, and in particular it provides a new sealing unit which can be advantageously applied and used in automatic lines for the production and sealing of bottles containing drugs. sterile injectable or similar substances, so as to also produce very positive effects on the production cost of these sealed bottles.

Furthermore, the bottle sealed with the sealing unit of the invention, in addition to being able to be packaged in a convenient and advantageous way, guarantees an excellent and stable sealing over time of the container containing the lyophilized drug inside it, as well as any other substance or similar compound, in liquid or powder form, prepared in a wide variety of ways

Variants

Without prejudice to the basic concept of the present invention, it is also clear that modifications and further improvements may be made to the sealing assembly described up to now, without thereby departing from the scope of the invention itself.

For example, according to a variant of the sealing unit of the invention, indicated with 110 and represented in Fig. 11, in which the corresponding parts are indicated with numerical references increased by 100 with respect to the preferred embodiment 10 described above, the seal 110 is provided, along the outer cylindrical surface of the respective head 110a, with a circumferential recess 110d, instead of a circumferential protrusion, as in embodiment 10.

Correspondingly, in this variant 110, the intermediate basket 120 is provided, in the respective cavity 120a, with a circumferential projection 120d, which is adapted to cooperate with the recess 110d to retain the sealing cap 110, once inserted into the intermediate basket 120 .

The sealing unit has been previously described, in the preferred embodiment 10, with specific reference to a use for sealing vials containing a lyophilized drug, or vials that receive and are preliminarily filled with a drug, in liquid form, which it is then lyophilized inside the bottle in a lyophilization chamber, in which subsequently the bottles, once the lyophilization process is complete, are sealed inside the lyophilization chamber itself.

However, it is clear that the concept of the present invention can be applied and also applies to sealing units intended to seal bottles, with mouths of different diameters, containing drugs that are not lyophilized, and therefore prepared in different ways, such as drugs and substances, injectables. , in the form of powder and / or the like.

Obviously, in this case, the sealing cap, corresponding to the sealing cap 11 of the embodiment 10, will be devoid of the slot for venting the vapors produced by the freeze-drying process, since it only performs the function of hermetically sealing the mouth. the container containing the drug or injectable substance.

Correspondingly, the packaging process of the sealed bottle does not include the intermediate step of lyophilization, so that the sealing unit, once it has been placed and mounted on the mouth of the container containing the injectable drug, is immediately pressed so as to cause the complete insertion of the sealing cap into the mouth of the container.

Claims (13)

CLAIMS 1. Sealing assembly (10) for vials containing sterile injectable drugs or similar substances, comprising: - a sealing cap (11) adapted to close and seal an opening or mouth (20b) formed in a containment body or container (20a) of a bottle (20) containing a sterile injectable drug (F); - an intermediate basket (12), able to house and cooperate with said sealing cap (11); And - a locking ring nut (14), adapted to be housed in a respective cavity (14a) and to cooperate with said intermediate basket (12), in which said intermediate basket (12) is constituted by a hollow cylindrical body (12b, 12c), and by a circular crown (13), in turn formed by a plurality or row of petals (13a) which extend from said hollow cylindrical body (12c) and are inclined towards the outside, in an undeformed configuration (C) of said intermediate basket (12), said sealing unit being characterized by what said hollow cylindrical body (12b, 12c) of the basket intermediate (12) is able to house and hold said sealing cap (11) inside it, and from what said locking ring nut (14) is able to engage said intermediate basket (12) in a first (13â € ™) and in a second area or engagement seat (13â € ™ â € ™) formed on the external surface of said intermediate basket (12), in which, in the production of the sealed bottle (20) with said sealing group (10), the sealing group (10) is preliminarily prepared in a pre-assembled configuration (CP), in which the locking ring (14) engages the intermediate basket (12) in said first engagement area (13â € ™) and said sealing cap (11) is held in said intermediate basket (12), subsequently, the sealing unit (10), in said pre-assembled configuration, is mounted on the mouth (20b) of the respective bottle (20) to be sealed, with the sealing cap (11) at least partially inserted in said mouth (20b ), And finally, the locking ring nut (14) is subjected to an external pressure (P), so as to push and completely insert, through the intermediate basket (12), the sealing cap (11) into the mouth (20b) of the bottle (20), and therefore seal it, e in which the locking ring nut (14), due to the effect of the external pressure (P) applied on it, disengages from said first engagement area (13â € ™), formed on the external surface of the intermediate basket (12), and therefore advances axially (X1, X2) until it engages said second engagement zone (13â € ™ â € ™), formed on the external surface of the intermediate basket (12), so as to close and engage the petals (13a) of the crown ( 13) of the intermediate basket (12) in an undercut seat (20e) formed in the area of the mouth (20b) of the bottle (20), and therefore stably block the various pieces (11, 12, 14) of the sealing group (10 ), once the sealing cap (11) has been completely inserted into the mouth (20b) of the bottle (20) to seal it. Sealing assembly (10) according to claim 1, wherein said first engagement zone or seat corresponds to a plurality of first recesses (13d) which are formed in the attachment zones of the petals (13a) of the crown (13) to the hollow cylindrical body (12c) of the intermediate basket (12) and define as a whole a first circumferential recess (13â € ™) facing the outside of said intermediate basket (12), and wherein said second engagement area corresponds to a plurality of second recesses (13e) which are formed in the tip areas of the petals (13a) of the crown (13) of the intermediate basket (12) and define as a whole a second circumferential recess (13â € ™ â € ™), also facing the outside of the intermediate basket (12), said first and said second circumferential notches (13â € ™, 13â € ™ â € ™) being able to receive and engage a corresponding circumferential protuberance (14d) formed in the internal cavity (14a) of said locking ring nut (14). 3. Sealing assembly according to claim 2, wherein said sealing plug (11) is formed by a first cylindrical portion (11a), or head, of larger diameter, and by a second cylindrical portion (11b), or stem , of reduced diameter, wherein said first cylindrical portion (11a), of larger diameter, of the sealing plug (11) defines along its outer cylindrical surface a circumferential projection (11d), in which said second cylindrical portion (11b), of reduced diameter, forms a slot (11c) suitable to allow, during a freeze-drying phase, the exit from the sealing cap (11), partially inserted in the respective mouth (20b), of the vapors that are products of the drug contained in the bottle (F), e in which said hollow cylindrical body (12b, 12c) of the intermediate basket (12) has on its internal surface a circumferential recess (12d) suitable for receiving and housing said circumferential projection (11d) defined on the external surface of said first cylindrical portion (11a ) of the sealing plug (11), in order to engage and retain said sealing plug (11) in said intermediate basket (12). Sealing assembly (10) according to claim 2, wherein said locking ring nut (14) comprises: - a cylindrical portion (14c) which has on its internal surface said circumferential protuberance (14d) capable of engaging said first and said second circumferential notches (13â € ™, 13â € ™ â € ™) formed on the external surface of the intermediate basket (12) , And - a protective cover (14b), fixed on said cylindrical portion, which is adapted to protect the insertion and perforation area of the sealing cap (11) with the needle of a syringe, in which said cylindrical portion (14c) is made with a sheet of a metallic material, in particular aluminum, and is suitable, during the advancement (X2) of the locking ring nut (14) caused by the external pressure (P) applied thereon, to cooperate with the petals (13a) of said crown (13) to flex them and bring them into engagement with said undercut seat (20e), and in which said protective cover (14b) is made of plastic material and is designed to be removed from said cylindrical portion (14c), at the time of use of the bottle, to allow the insertion and perforation of the respective sealing cap (11) with syringe. 5. Sealing assembly according to any one of the preceding claims, wherein the pieces of said sealing assembly, i.e. said sealing plug (11), said intermediate basket (12), and said locking ring nut (14) are configured and cooperate reciprocally in the relative engagement areas so that, when said locking ring nut (14) is subjected to said external pressure (P), said locking ring nut (14) advances integrally with said intermediate basket (12) and with said sealing (11) for a determined portion (X1) until said sealing cap (11) is completely inserted into the mouth of the bottle and abuts against an edge of said mouth (20b), and in which, once said sealing cap (11) has made abutment against the edge (20dâ € ™) of said mouth (20b), said locking ring nut (14) disengages from said first engagement area (13â € ™ ) and advances for a further length (X2) relative to said intermediate basket (12), until said locking ring nut (14) engages said second engagement area (13â € ™ â € ™) formed on the external surface of the intermediate basket , in such a way as to close and engage the petals (13a) of the crown (13) of the intermediate basket (12) at the same time in said undercut seat (20e) formed in the mouth area (20b) of the bottle (20). 6. Sealing assembly (10) according to claim 1, wherein, with said locking ring nut (14) engaged with said first engagement zone (13â € ™) formed on the outer surface of the intermediate basket (12), the crown ( 13) of petals (13a) of said intermediate basket (12) has an external diameter (D1â € ™) which is smaller than that (D) of the containment body (20a) of the bottle (20) to be sealed with the group of sealing. 7. Sealing assembly according to any one of the preceding claims, in which the petals (13a) of the crown (13) of the intermediate basket (12) each have a tooth (13c) projecting towards the inside of the intermediate basket in the tip area (12), said tooth (13c) being able to engage said undercut seat (20e) formed in the mouth area (20b) of the bottle (20), when the sealing assembly (10) is pressed to fully insert the seal (11) in the mouth (20b) of the bottle to seal it. 8. Sealing cap (11) for sealing bottles (20-1, 20-2, 20-3) containing injectable sterile drugs or similar substances, comprising: - an upper part or head (11a), with a larger diameter; - a lower part or stem (11b), of smaller diameter, suitable to be inserted in a mouth (20b) of a bottle (20, 20a) to seal it; And - a plurality of protrusions or buttons (11e) uniformly distributed along a circumference along the external cylindrical surface of said shank (11b), in which, when the sealing cap (11) is partially inserted in said mouth (20b) during the production and sealing of the bottle (20) in a respective automatic production and sealing line (LCA), said projections (11e) they are designed to abut against an edge surface (20dâ € ™) on which the mouth (20b) of the bottle (20, 20a) faces externally, so as to hold the sealing cap (11) stably, once partially inserted , in a correct axial orientation with respect to said mouth (11b), during the handling of the bottle in said automatic production and sealing line (LCA). 9. Sealing cap (11) according to claim 8, further comprising a lateral slit (11c), formed in said stem (11b), to allow the escape of the vapors (V) produced by the freeze-drying of the drug contained (F) in the bottle (20, 20a), in which said protrusions (11e) are arranged along a circumference at the sides of said slot (11c) and are six in number. Bottle (20) for containing a sterile injectable drug (F), characterized in that it comprises and is sealed by a sealing assembly according to any one of claims 1 to 7. 11. Process for manufacturing and sealing vials (20-1, 20-2, 20-3) containing a sterile injectable drug or similar substance, comprising the following steps: - provide a sealing unit (10) consisting of: - a sealing cap (11) adapted to close and seal an opening or mouth (20b) formed in a containment body or container (20a) of a bottle (20) containing a sterile injectable drug (F); - an intermediate basket (12), able to house and cooperate with said sealing cap (11); And - a locking ring nut (14), adapted to be housed in a respective cavity (14a) and to cooperate with said intermediate basket (12), - pre-assembling (fp-1, fp-2, fp-3) the parts (11, 12, 14), making up said sealing group (10), in a pre-assembled configuration (CP) in which said sealing cap sealing (11) is housed in and held by said intermediate basket (12); - mount (f-2) said sealing group (10), in the pre-assembled configuration (CP), on the mouth (20b) of a bottle (20, 20a) to be sealed, so that the sealing cap (11) is at least partially inserted in said mouth (20b); And - press (f-5, f-6) the sealing unit (11, 12, 14) against the mouth (20b) of the bottle in order to fully insert the sealing cap (11) into the mouth (20b) of the bottle so ¬ to be sealed, and also to lock the sealing cap (11), once inserted in the mouth, by means of the locking ring nut (14) and the intermediate basket (12) of the sealing group (10). 12. Process according to claim 11, comprising a lyophilization step (f-4) which is carried out, after having mounted the sealing unit, in the pre-assembled configuration (CP), on the mouth (20b) of the bottle, with the sealing cap (11) partially inserted in said mouth to allow freeze-drying vapors to escape (V). 13. Line (LCA) for the high-speed production of sealed vials (20-1, 20-2, 20-3) containing a sterile injectable drug (F) or a similar substance, characterized by what it uses, to seal bottles, a sealing assembly according to any one of claims 1 to 7, and implements a method for manufacturing and sealing the bottles according to claim 11.