FR2477014A1 - Making liq. tight hard gelatin capsules - by applying viscous glue inside separated capsule top, then closing over filled capsule body - Google Patents

Abstract

Process for making hard gelatin capsules liq.-tight and for storing, in these capsules, granular, powder or liq. prods. (e.g. pharmaceuticals) comprises first separating the head (A) of the capsule. A band of viscous glue is placed inside (A) a certain distance from its end, while the body (B) of the capsule is filled. (B) is then fitted back into (A). Pref. before and during joining of (A) and (B) a controlled atmos. is maintained inside and outside the capsule, its pressure being sufficiently low that after closure the pressure inside the capsule is at most equal to ambient pressure. The atmos. in the capsule may include a tracer. Pref. the glue is a soln. of gelatin or PVP in water or aq. alcohol. An appts. for this process is also claimed. The capsules are treated automatically and rapidly (several per sec.) and are absolutely liq. tight, even for very freely-flowing liq. There are no problems associated with glue on the outside causing capsules to stick together.

Description

The invention relates to a method and a device for sealing hard gelatin capsules and for conditioning a dose of liquid product in the capsule thus sealed, the sealing and packaging operations being capable of being carried out automatically at a high rate. by ensuring on a device a production of several capsules per second.

 Increasingly, in particular for the packaging of solid or liquid medicaments, envelopes generally made of gelatin, called capsules. A distinction is currently made on the one hand, capsules made of hard gelatin and more commonly designated by the simple term "capsules", and soft gelatin capsules more commonly designated by the term "capsules", the former being used for packaging of solid medicines, in the form of granules or powders, while the latter are more particularly reserved for the packaging of liquid medicines.

The hard gelatin capsules or "capsules" consist of two distinct parts, namely the "cap" and the "body" coming to fit one into the other to constitute the complete capsule. The cap and the body are produced by the same process consisting in immersing in a gelatin solution the end of a mandrel whose shape corresponds to the interior volume of the cap or of the body, then removing the mandrel from the solution and let the gelatin layer thus deposited dry, which is then removed like a thermowell. In practice, a large number of mandrels carried by a conveyor which provides; successively immersing the ends of the mandrels, then passing them through a dryer, which makes it possible to achieve very high production rates per unit of time.

Bes soft gelatin capsules or capsules are manufactured by a completely different process, which consists in passing between two cylinders of parallel axes, and provided with alveoli, two strips of soft gelatin between which is the product to be packaged, which is in principle in liquid form. In the vicinity of the plane containing the axes of the cylinders, the two strips of gelatin are strongly compressed between the surfaces, then very close to each other, of the two cylinders, so that the liquid product
to be conditioned is pushed back between the two strips of gelatin
at the location of the cells formed in the cylinders, and what
on the other hand, the two gelatin strips are welded together
on the periphery of these cells under the pressure exerted on
them by the cylinders. The sealed capsules thus formed and
containing the liquid product are then detached from the strips
gelatin. This process also allows very high rates
but it is much less economical as far as
the use of gelatin as the soaking method used
for the manufacture of hard capsules, because the parts of the strips
of soft gelatin between the capsules are
lost. Apart from this higher gelatin expenditure,
another disadvantage of capsules compared to capsules of
res is that the packaging of the product as we just
see it, must be done at the same time as the
manufacture of the capsule shell Ût on the same instal
This poses difficult problems because, generally
the lots of drugs to be packaged correspond to a
relatively small number of capsules compared to the
production capacity of the cap manufacturing facility
sure. It follows that this installation must be frequently
stopped and cleaned to switch from a batch of medication to a
formula determined with a batch of another formula. These stops
frequent significantly lower the average rate of pro-
installation duction, which adds to the expense
higher material to further increase the price of the condi
However, in the case of capsules of
res where the manufacture of the capsule shell and the opera
conditioning operations are carried out on separate installations,
we can provide for the conditioning of installations of which
the rates are adapted to the importance of the series to be treated,
so these facilities are operating at full capacity and
that this is added to the savings made on the material
keeps the price of packaging in hard capsules
as low as possible.

Like on the other hand, in many cases it would
better to administer the drug in a liquid form
rather than in a less directly assimilated solid form,
it is clear that the possibility of using hard capsules, not only for packaging the medicament in powder or granular form as is currently the case, but also in liquid form, would be of greatest interest. However, the problem is particularly difficult since gelatin being a material capable of evolving from the dimensional point of view, it is necessary to provide during the manufacture of caps and hard capsule bodies, a large diametrical clearance to allow the bottling without difficulty the cap on the body. So that despite this important play the cap after fitting does not separate from the body during a manipulation to which the capsule will necessarily be subjected, so-called "clipping" devices are provided, for example by an annular depression on the corresponding body with an annular bead directed inwards on the cap, depression and bead whose interpenetration during the fitting of the cap on the body, will hold these two parts of the capsule together. This clipping which provides a certain locking effect between the cap and the body, however does not in any way remedy the lack of tightness of the assembly due to the large clearance that it is necessary to provide between these two parts to allow fitting .

Among the many attempts that have been made to allow the sealing of hard capsules and their use for the packaging of liquid products, the following may in particular be cited:
We tried to make a tight seal between the cap and the body by coating the hard capsule externally after fitting with an adhesive which, after drying, will form a tight film. However, in addition to the fact that it is difficult to give this film sufficient thickness to make a tight junction between the cap and the body, given the large diametric clearance existing at the junction between these two parts, the drying of such a layer of glue is particularly long and poses difficult problems due to the fact that as long as this drying is not completely achieved the capsules cannot come into contact with one another.

Another attempt consisted in coating-with a viscous glue the external part of the body of the hard capsule penetrating at the casing in the cap. But the drawback is that, during ltemboStageb, part of this glue is forced back by the cap towards the lower part of the body of the capsule, where it forms a bead and where it also poses a drying problem which is extremely difficult to solve.

It has also been tried to incorporate into the liquid medicament intended to be packaged in the capsule, additions giving it a thixotropic nature, so that this medicament acquires, after being thus conditioned in the capsule, a viscosity sufficiently high to not not pour out by the play existing between the cap and the body and can, however, upon its arrival in the stomach where it will be subjected to a certain kneading, resume sufficient fluidity. But in addition to the fact that the additions thus incorporated into the liquid medicament must be of such a nature and be used in such a quantity, that this addition proves in many cases inadmissible and in other harmful cases experience shows that the results are not satisfactory. Indeed, the phixotropic state of the product is unstable, in particular due to the vibrations which the capsules undergo during the mantrulations and transport, and after some time, leaks appear.

 The object of the invention is to remedy these difficulties and to create a process making it possible to make hard capsules perfectly impermeable to liquid products, even when these have great fluidity.

 To this end, the invention relates to a method characterized in that, after having separated the cap of the capsule from the body of the capsule, an internal layer is deposited inside this cap and at a certain distance from the edge of this cap. strip of viscous glue, while introducing into the body of the capsule the dose of product to be conditioned, then the body thus filled is fitted into the cap thus prepared.

 The process according to the invention defined above has, compared to known solutions, the advantage that the supply of glue takes place inside the cap in a well-defined zone relatively distant from the edge of this cap, if although during nesting, this glue tends to be pushed back towards the inside of the capsule and cannot, in any case, exude inside. As a result, the drying problems which have hindered the above-mentioned attempts do not arise here, and the capsules can come into contact with one another and be handled immediately after fitting, while drying can continue throughout the time required during the generally long period which elapses between the casing and the use of the capsule.

In addition, the glue was chosen to be sufficiently viscous so that sealing was ensured from the casing.

The invention also relates to a device for implementing the method defined above, this device being particularly well suited to carrying out at very high speed the operations necessary for sealing the capsule and for packaging granulated products, in powder or liquid form, in the capsules thus prepared
The invention will be explained in more detail with reference to an exemplary embodiment shown without limitation in the accompanying drawings, in which:
FIG. 1 represents in axial section, a capsule in which a product, such as a drug, is packaged,
FIGS. 2a to 2i are schematic representations in elevation and in partial section, of the device according to the invention during the various phases of its operation,
FIG. 3 is a schematic axial section of a first embodiment of the part of the device according to the invention ensuring the setting and transfer of the adhesive, in the cap of the capsule,
- Figure 4 is a variant of the part of the device shown in Figure 2.

A hard gelatin capsule designated as a whole by i, consists of a cap 2 and a body 3, fitted into the cap 2. The capsule 1 is filled to a certain distance from the upper edge of the body 3 by a product 4, such as a solid or liquid drug. The assembly constituted by an annular curve 5 concave towards the outside on the body 3 and a corresponding annular curve 6 concave towards the outside on the cap 2, constitutes the "clipping" ensuring the cohesion between the cap 2 and the body 3 despite the relatively large diametral clearance which must be provided between these two parts, to allow their nesting.

Figures 2a to 2i schematically show in elevation and in partial section, the device according to the invention allowing to perform at high speed the sealing and filling operations of the capsule.

 The assembly, designated by 7, of the device is movable in rotation about a vertical axis 0-0 'indicated in line points in FIG. 2a and whose situation with respect to the device 7 is recalled in FIGS. 2b to 2i by the arrow F.

 The assembly 7 is broken down into three sub-assemblies, namely, going from the top to the bottom, the sub-assemblies 71, 7 "and 7" t The assembly 7 'essentially consists of two necks seals 8 and 9 moving vertically and interconnected by a pendulum 10 pivoting about a horizontal axis II.

A liquid distributor piston 12 slides coaxially in the slide 8 and is extended downwards by a liquid distributor nozzle 13. A glue distributor piston 14 slides coaxially in the slider 9 and has along its axis, a bore 15 through which the glue to be dispensed arrives.

 The subassembly 7 "essentially comprises a slide 16 with horizontal displacement inside which horizontally slides a support 17 carrying a vehicle 18.

In addition, a stop block 19 is integral with the slide 16.

The slide 16 and the support 17 are offset perpendicular to the plane of the figure and behind this plane relative to the stop block 19 and to the vehicle 18.

The subassembly 7 ′ essentially consists of a support 20 capable of moving vertically and which successively carries, going from left to right in FIGS. 2a to 2i, the following members:
- firstly a bucket grout 21 moving vertically, urged in abutment up against a shoulder of the support 20 by a spring 22 and comprising, at its upper part, a housing 23 capable of being connected to a vacuum pipe 24 ,
- secondly a vertical finger25,
- Thirdly, an adhesive gripping and transfer member 26 of essentially vertical orientation and which goes further described in more detail below.

 According to Figure 3, the member 26 comprises a tube 27 inside which is a mandrel 28. A membrane 29 is held between the tube 27 and the mandrel 28 and the upper part of this membrane is susceptible to further swelling by the compressed air introduced by means of holes 30 in the mandrel 28.

The assembly which has just been briefly described operates in the following manner
Referring to FIG. 2a, the slide 16, as well as the support 17, are shifted as far as possible to the left, so that the vehicle 18 occupies its left external position in which it is vertically on the one hand, from the nozzle 13, and, on the other hand, from the housing 23. The support 20 is in its low position,
Via a conventional feeding system 31, not shown in detail since it is not part of the invention, and which distributes and directs empty capsules 1 from a hopper, not shown, where they are in bulk, an empty capsule is introduced into the vehicle 18, so that the edges of the cap of the capsule 1 come to rest on a shoulder formed in this vehicle 18, while the body of the capsule 1 protrudes towards the down beyond this shoulder.

 From the situation shown in Figure 2a, the support 20 rises vertically, so that the slide 21 abuts on the underside of the vehicle 18 and that the housing 23 comes to cover the lower part of the body of the capsule . Via the pipe 24, a vacuum is then created in the housing 23 and the support 20 is again lowered, drawing the body 3 of the capsule 1 by suction, while the cap 2 of the latter remains on the shoulder of the vehicle 18. The slide 16 then moves to the right so as to bring the vehicle 18 and the cap 2 of the capsule to the vertical of the finger 25, thus achieving the situation visible in FIG. 2b. distribution of glue is carried out in an internal groove 32 of the slide 9, by means of the holes 15 of the piston 14. This distribution is done in refusal, and when the groove 32 is filled, an overflow valve 33 eliminates the 'excess glue.

 Starting from the situation shown in FIG. 2b, the support 20 rises vertically again. As the housing 23 is by construction placed vertically from the nozzle 13, this upward movement of the support 20 causes the capsule body 3 to come to cap the nozzle 13 from below. Simultaneously the finger 25 penetrates into the cap 2 of the capsule. If for some reason the capsule had not been separated, that is to say if its body had not been sucked by the housing 23, the upward movement of the finger 25 would have expelled from the vehicle t8 the whole of this capsule thus not separated .The emptiness of the vehicle 18 thus caused would have been detected by automatic control means not shown because they are known per se and not forming part of the object of the invention, and these control means would have prohibited on the device 7 considered , performing subsequent operations such as dispensing liquid or glue.

 The upward movement of the support 20 also brings the glue pick-up and transfer member 26 into contact with the piston 14 of the slider 9, while this slider moves downwards bringing its internal groove 32 filled with glue facing the membrane 29 lining the end of the member 26.

We are then in the situation shown in Figure 2c.

In this situation, the membrane 29 of the member 26 is inflated by compressed air arriving through the bore 30 as can be seen on the left side of FIG. 3c
In doing so, the membrane comes into contact with the adhesive deposited in the groove 32, then the hole 15 being brought to the open air, the membrane 29 resumes its original shape by carrying on its surface a strip of glue 34 taken from the groove. 32. At this moment the support 20 begins a new downward movement, while a dose of liquid begins to be distributed progressively in the body 3 of the capsule via the nozzle 13. The determination of this dose of liquid is effected by a metering device which is not shown because it is conventional and does not form part of the object of the invention.

The dispensing of the liquid dose ceases when the upper edge of the body 3 of the capsule, in its downward movement, arrives a little below the nozzle 13. We are then in the situation shown in FIG. 2b.

From this situation, the support 20 continues its downward movement until, successively, the upper end of the finger 25 and the upper end of the member 26 are below the underside of the vehicle. 18.

The slide 16, as well as the support 17, are then offset in their extreme positions to the right, positions for which the axis of the vehicle 18 is situated vertically then gane 26, while the upper opening of the vehicle 18 is covered by the stop block 19. We are then in the situation shown in Figure 2e.

From this situation, the support 20 resumes an upward movement, which has the effect of penetrating the upper end of the member 26, that is to say the membrane 29 carrying the strip of glue 34, in the cap 2 of the capsule held between the shoulder of the housing 18 and the stop block 19. We are then in the situation shown in FIG. 2f 0 The membrane 29 is then inflated, then immediately deflated again, this having for effect of transferring the strip of glue 34 on the internal face of the cap 2 of the capsule.

 The support 20 then moves down again so as to bring successively, on the one hand the member 26 and on the other hand, the upper edge of the body 3 of the capsule carried by the slide 21, below the underside of the vehicle 18. The slide 16 then moves in its extreme position to the left, bringing the axis of the vehicle 18 and therefore the axis of the cap 2 of the capsule to the vertical of the axis of the slide 21 and therefore of the axis of the body 3 of the capsule. We are thus in the position shown in Figure 2g.

 From this position, a new upward movement of the support 20 has the effect of bringing the upper face of the slide 21 into abutment against the lower face of the vehicle 18, as can be seen in FIG. 2h. A pusher 35 moving upwards inside the slide 21 then fits the body 3 of the capsule into the cap 2 held in place by the stop block 19 and the inner face of which carries the strip of glue 34. We realize thus a tight junction of the two constituent parts of the capsule.

The slide 16 then moves to the right, driving the stop block 19 and thus releasing the upper opening of the vehicle 18, while the pusher 35 continues its upward movement until its upper end reaches the level of the upper face. of the vehicle 18. The capsule 1 is then completely extracted from the vehicle 18 and it is ejected laterally into a chute 36 using a compressed air blower 37 (see FIG. 2i).

The succession of operations which has just been described and which is illustrated in FIGS. 2a to 2i, corresponds to a succession of angular positions of the device 7 around the vertical axis 0-0 '. Two cases can then be envisaged: - or else the device 7 rotates in a discontinuous movement at the
rotation of the axis 0-0 'and the displacements of the different organs
(support 20 slide 162 etc ...) are made during the ar
rOt of the device 7 in a determined angular position and - or else the device 7 is driven in a continuous movement around
of the 0-0 'axis and the different displacements of evo organs
ques above take place while the device 7 by
runs a specific angular area.

Both solutions are possible, but we prefer for very high rates (for example 10 capsules per second or more) the solution in continuous kinematics which generally makes it possible to reach higher rates and to operate the installation in better conditions.

 FIG. 4 represents a variant 26 ′ of the device 26 for taking the adhesive transfer shown in FIG. 3.

The device 26 'differs from the device 26 in that the deformation of the membrane 29' instead of being obtained by the action of compressed air is obtained by purely mechanical means.

In fact, the membrane 29 ′, the lower part of which is gripped between a tube 27 ′ and a mandrel 28 ′ has a relatively large thickness at its upper part, therefore a relatively high rigidity. When the upper part of the membrane abuts on the bottom of the cap 2 of the capsule itself in abutment on the abutment block 19, this thicker and more rigid part transmits the abutment force to the intermediate part of the membrane which is therefore deformed and which is applied to the inner face of the cap 2. As soon as the pressure exerted by the stop stops, the membrane returns to its initial shape.

 In the foregoing description, only the filling of the capsule body with a liquid product has been considered. Of course, the invention also applies in the case where a dose of a granulated or pulverulent product is introduced into the body of the capsule, although in this case the sealing of the capsule is no longer as necessary.

 With regard to the characteristics of the adhesive to be used, it was previously indicated that it would be advantageous to use an adhesive of high viscosity, to allow better sealing off the necessarily significant clearance existing at the start between the cap and the body of the capsule. With regard to the nature of the adhesive used, experience has shown that good results are preferably obtained with solutions of gelatin or polyvinylpyrolidone in water or in a mixture of alcohol and water.

Claims (5)

R B V E N D I C A T. I O N S 1.- Method for sealing hard gelatin capsules and for conditioning in the capsules thus prepared  products, such as drugs, in 2 forms  granules, powders or liquids, process characterized by what, after separating the capsule cap from the body of the capsule, we put it inside this cap and at a -cer- distance from the edge of this cap, a strip of glue viscous, while introducing into the body of the capsule  the dosevde product to be packaged, then the body is then fitted so filled in the cap thus prepared.  2.- Method according to claim 1, characterized  in that the glue used is a solution of gelatin or  polyzinylpyrolidone in water or in a mixture of water and alcohol.  3.- Device for implementing the process according to any one of claims 1 and 2, device  characterized in that it constitutes an assembly (7) susceptible  to rotate around a vertical axis (0-0 ') and consisting of  three subsets (71, 7ns 7n () ranging from top to bottom  the bottom, the upper sub-assembly (7S) comprising essential two slides (8 and 9) with vertical displacement, articulated  strip between them by a pendulum (10) pivoting about an axis horizontal (11) a plunger (12) for distributing the neck smoothing coaxially inside 11 of the slide (8) and pro  running down by a nozzle (13) while a piston (14) dispensing glue slides coaxially inside slide of the slide (9), the intermediate sub-assembly (7 ")  being essentially constituted by a slide (16) suscep  tible to move horizontally and secured to a block of  stop (19), while a support (17) slides coaxially with  inside the slide (16) and carries a vehicle (18), the  lower sub-assembly (7 "') being essentially constituted by a support (20) capable of moving vertically and  bearing successively from the periphery of the device (7) towards the axis (0-0 '), first of all a slide (21) suscep  tible to move in abutment up under the action of a  spring (22), this slide (21) comprising at its end su  a housing (23) capable of being connected to a cana  reading of vacuum (24) and intended to receive the body (3) of the capsule (1), and this slide (21) comprising a coaxial pusher (35), secondly a vertical finger (25) t in third place a member (26) for taking and transferring glue, this member having an essentially vertical orientation, the housing (23) at the upper end of the slide (21) being by construction placed vertically above the nozzle (13 ), while the adhesive transfer taking member (26) is by construction, placed vertically on the axis of the slide (9), and the axis of the vehicle (18) being capable of being brought by the displacement of the slide (16) and of the support (17) respectively vertical to the housing (23) or vertical to the finger (25) or again, vertical to the member (26) for gripping and transferring glue .  4.- Device according to claim 3, characterized in that the member (26) for taking and transferring glue, is essentially constituted by an extensible membrane (29) in the form of a thimble whose open lower part is clamped between a tube (27) and a mandrel (28) inside this tube, while its closed upper part is capable of being inflated under the action of compressed air arriving through bores (30) of the mandrel (28).  5.- Device according to claim 3, characterized in that the member (26 ') for taking and transferring glue is essentially constituted by an extensible membrane (29') in the form of a glove finger, the lower end of which open is clamped between a tube (27 ') and a mandrel (28t) inside this tube, the closed upper end of this membrane (29f) having a thickness and therefore greater rigidity than the intermediate part of the membrane.