DE3704992A1 - METHOD AND DEVICE FOR FILLING AND SEALING CONTAINERS WITH A NON-LATCHING FIT - Google Patents

Description

The invention relates to a method and a device for filling and sealing containers with non-latching Fit.

It is known to use compression-molded molded articles made from natural materials Starch and hydrophilic materials, e.g. B. gelatin Manufacture injection molding. Place containers of this type preferred carriers for filling with pharmaceuticals, Food, chemicals and the like; they will in particular in the form of pharmaceutical dosage form capsules for dosed administration of drugs. These Containers consist of a container lower part (or receiving part) and a closure part, at least regularly one of the two parts and often both parts are provided with matching ridges and grooves, a snap effect and thus a good closure between the two parts. Pharmaceutical Capsules have comparatively small dimensions. For filling the containers with pharmaceutical agents (Active ingredients) the snap effect is of particular importance, because this is a random (unwanted) or must also prevent deliberate opening of the capsules. According to the current methods, the snap lock through an undercut of high accuracy with a Depth of approximately 0.03-0.15 mm in the lower part and / or closure part reached. A smaller undercut results a poor closure while a too large one Undercut to crack formation, especially in the lower part leads.

Snap locks also executed with high accuracy have various disadvantages. The wall thickness a pharmaceutical capsule must be as small as possible.  

As a result, the wall thickness of the base is different from that of the closure part different. Because of your different thicknesses, the two parts show an unequal Dimensional dynamics among non-constant Conditions, especially when the humidity changes to a different geometry of the both parts and leads to (mechanical) stresses. Under certain conditions this can lead to a blasting of the Lead capsule so that then filled powder or liquids leak. In particular, also in the filling machine Difficulty closing both capsule parts arise.

The manufacture of such snap closures is also technically complex. In particular, (sliding) Slider or separable jaw molding tools necessary, with the moving molds leaving marks, which as bumps on the surface of the Shaped appear. Because of the necessary slider and baking, the mold has more sliding parts, higher wear, higher working pressures or closing forces, higher susceptibility to faults and therefore longer Downtimes and higher operating costs. In addition sliders (or slides) cause some Mold destabilization. In particular can also fewer cavities or cavities per available Area unit are provided, which significantly increases the output reduced.

It has now been shown that all of these described Disadvantages can be eliminated if you have pressure molded parts used with a non-latching fit and these moldings to the invention to be described later Way sealed. These molded parts preferably form a container with a substantially continuous one Outside surface.  

The invention thus relates to a method for filling and sealing containers with non-latching (non locking) fit by printing forms and preferably Injection molding from natural strength or at least another hydrophilic material or mixture of compounds of this type are, a container base and a closure part have and preferably in the form of pharmaceutical (dosage form) capsules present, which is characterized is that

• a) the contents in a container of the specified type, the is free of a snap lock, is filled,
• b) a sealing liquid with either the whole Fitting surface of the closure part, which in the closed Condition the (assigned) fit area of the container Bottom touched, or with an element of this Fitting surface of the closure part and / or with the entire Fit surface of the lower part, which in the closed Condition of the container the (assigned) Touched fit surface of the closure part, or with an element of this fit surface of the lower part in Is brought into contact and
• c) then the lower part with the closure part for permanently or irrevocably closed containers is put together.

Starch is the naturally occurring vegetable To understand carbohydrate, which is mainly from amylose and amylopectin. You will z. B. from potatoes, Rice, tapioca, corn, cereals such as rye, oats, wheat, and other plants. Such strength can be to compact using pressure and elevated temperature Process moldings with high precision. The manufacturing process for pressure molding, especially for injection molding under pressure and elevated temperature, d. H.  the process conditions, as well as the possible additions such as extenders, lubricants, plasticizers and / or dyes are in European Patent Application No. 84 300 940.8 (Publ. No. 118 240) and apply (also regarding preferred temperatures, pressures and Moisture content) also for the present invention.

Under the term "other hydrophilic materials" are understand such hydrophilic materials that are for the Production of the container according to the invention, in particular in the form of pharmaceutical capsules.

"Other hydrophilic materials" are polymeric materials, for example gelatin; vegetable proteins, such as sunflower, Soybean, cottonseed, peanut, rapeseed proteins; Blood proteins; Egg proteins; acylated proteins; water-soluble polysaccharides, such as alginates, carrageenans, Guar gum, agargar, gum arabic and related gums (Ghatti, Karaya and tragacanth gum), pectin; water soluble Derivatives of cellulose, e.g. B. Alkyl celluloses, hydroxyalkyl celluloses and hydroxyalkyl alkyl celluloses, such as methyl cellulose, hydroxymethyl cellulose, Hydroxyethyl cellulose, hydroxypropyl cellulose, Hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, Hydroxybutylmethyl cellulose, cellulose esters and hydroxyalkyl cellulose esters, e.g. B. Cellulose Acetyl Phthalate (CAP), hydroxypropylmethyl cellulose (HPMCP); Carboxyalkyl cellulose, Carboxyalkylalkyl cellulose, carboxyalkyl cellulose esters, such as carboxymethyl cellulose and their Alkali metal salts,  water-soluble synthetic polymers such as polyacrylic acids and polyacrylic acid esters, polymethacrylic acids and polymethacrylic acid esters, Polyvinyl acetates, polyvinyl alcohols, Polyvinyl acetate phthalates (PVAP), polyvinyl pyrrolidone, Polycrotonic acids; phthalylated gelatin can also be used, Gelatin succinate, cross-linked gelatin, shellac, water-soluble chemical derivatives of starch, cationically modified Acrylates and methacrylates with e.g. B. a tertiary or quaternary amino group, such as the quaternized one Diethylaminoethyl group, and other similar polymers. Gelatin is preferred.

The manufacturing process for the specified others hydrophilic materials, especially for injection molding under increased pressure and temperature, are in European Patent Application 83 301 643.9 (Publ. 090 600), which describes the process conditions  indicates and details regarding possible additions, such as Extenders, lubricants, plasticizers and / or dyes contains and to which (including preferred temperatures, Pressures and moisture levels) hereby referred becomes. Hydrophilic materials of this type are e.g. B. in Robert L. Davidson, Handbook of Water-Soluble Gums and Resins, McGraw-Hill Book Company.

The in the two European patent applications mentioned 84 300 940.8 and 83 301 643.9 details described regarding the production of pressure-molded containers of the specified type and in particular with regard to the manufacture of pressure-molded pharmaceutical (dosage form) capsules, preferably by injection molding also for the invention.

The invention relates to compression molded, preferably injection molded or injected to the specified Containers that can be produced in this way, preferably in the form of pharmaceutical (dosage form) capsules.

Within the scope of the invention, the various specified hydrophilic materials mixed or can be combined with each other. These materials can inorganic fillers, such as the oxides of magnesium, Aluminum, silicon, titanium, etc. can be added. Extender concentrations of up to 50% are indicated however, preferably in the range of 3-10% on the weight of all components forming the container wall.

Examples of addable plasticizers are polyalkylene oxides, such as polyethylene glycols, polypropylene glycols, polyethylene propylene glycols; low molecular weight organic plasticizers, such as glycerol, glycerol mono-, di and triacetate; Propylene glycol, Sorbitol, sodium diethyl sulfosuccinate, triethyl citrate,  Tributyl citrate, etc., in a concentration of 0.5-15%, based on the weight of all components.

Dyes are, for example, known azo dyes, organic or inorganic pigments or naturally occurring Dyes. Inorganic pigments are preferred, like the known oxides of iron or Titanium, in a concentration of 0.001-10%, preferably 0.5-3%, based on the weight of all the container wall constituents.

They preferably have starch and / or the other hydrophilic Materials shaped containers have a water content from 10-20%, preferably 12-19% and in particular 14-18%, based on the weight of all the container wall constituents.

The sum of plasticizer and water is preferred at most 25%, preferably at most 20%, based on the weight of all components forming the container wall.

Although the invention is related to capsule forms described, it should include all types of containers, which are essentially hollow and from the specified hydrophilic materials can be produced and a sealed Form disposable containers. The container marks itself through an essentially uninterrupted Outside surface.

Compared to the two Europeans mentioned above Patent applications are the special feature of the invention in that the closure part and the lower part no snap bars or grooves in the container and therefore no snap locks of any kind exhibit. Those capsules are preferred in which the lower part and the closure part are completely deformation-free  let put together. Capsules of this type are new and Subject of the invention. Sealed capsules according to the Invention preferably have a practical at all points same wall thickness, so that (mechanical) tensions due to different dimensional dynamics under not constant conditions can be avoided.

Containers according to the invention are easy to manufacture, fill and seal. Because of the missing Snap lock, however, are relatively easy open or open on their own during further treatment, especially if the lower part and the closure part with high precision, but without deformation are merged. As a rule, they are in one another pushed surface segments only 0.5 mm to maximum 2 mm high.

It was therefore surprising to find that the Capsules don't open if you have at least one of them touching surfaces of the lower part or the closure part before finally sealing with a sealing liquid touches. In this way filling at high speed is made possible, this process before the irrevocable or final Closing the capsules is done.

This sealing liquid preferably contains water. This is preferably a mixture of water and an alcohol, preferably one with 1-4 C atoms, preferably Ethanol, propanol or butanol, especially ethanol or isopropyl alcohol, preferably ethanol, in one Water / alcohol ratio of 95: 5 to 40:60, preferably about 80:20 to 60:40, preferably about 70:30.

Other aqueous sealants are e.g. B. aqueous Solutions of sucrose, starch, mono-, oligo- and  Polysaccharides, glycerin and other polyols, glycol, Polyethylene glycols and / or propylene glycols, per se known anionic, cationic or amphoteric surface-active Agents, gelatin, polyvinyl alcohols, water-soluble anionic or cationic acrylic polymers in a concentration of 0.5-10% by weight, preferably 1-4 wt .-%, based on the total weight of the sealing liquid.

The water / ethanol mixture mentioned above is preferred.

For example, water alone causes excessive or inaccurately distributed wetting, which damages the Or the capsule. As a result of high sensitivity of the capsule wall to water the sealing liquid must be an exact local and allow quantitative wetting.

Of course, it takes some time for a sealing effect entry. So it was surprising determine that the closed invention Capsules without any opening signs or Process even damage and have it packed.

Through the precise local and metered application of the sealing liquid becomes an exact and fluid tight The container is sealed. The containers can only be opened by destruction after sealing will.

To achieve a faster seal, you can also the closed container or the closure or Warm the fitting point. Any heat source that the container or its contents are not damaged, can be used such as B. convection heat, such as by means of heated Air; electromagnetic radiation of a suitable frequency,  e.g. B. microwaves or infrared radiation, and ultrasonic energy, the temperature generated is not critical, provided that there is no damage to the capsule or its Content is caused. An acceleration of the sealing through such additional measures, however only necessary if necessary. Warming up to 30-50 ° C is usually sufficient. The heating can also be whole or partly by means of at a temperature between 30 ° and 100 ° C kept sealing liquid.

The contents can be solid, pasty or liquid. The Filling contents for pharmaceutical containers are known per se and correspond to the substances that come with the capsule wall are compatible and which are usually in pharmaceutical Hard gelatin containers are filled.

By using the (administration form) container according to the invention and their sealing result in addition the elimination of the disadvantages mentioned at the outset unexpected benefits. So it works, the wall thickness of the container to reduce greatly because of the mechanical stress due to the snap lock. This requires a significantly higher opening and opening speed of the container in gastric or intestinal juice as well as material savings and better volume utilization of the container.

The following are preferred embodiments of the invention explained in more detail with reference to the drawing. It shows

Fig. 1 is a side view of a container according to the invention,

Fig. 2 shows a section along the line II-II in Fig. 1,

Figures 3a to 3u held in an enlarged scale partial cross-sectional views of various embodiments. Of the stress free closure between container base and closure part, corresponding to the detail 18 in Fig. 2,

Fig. 4 shows a plan view of a filling / sealing machine for the inventive container

Fig. 5 a held on an enlarged scale section along the line VV in Fig. 4 by the filling / sealing machine associated with wetting and sealing station, and

Fig. 6 is a perspective view of a filling machine, ie a machine of the type shown in Fig. 4 with a wetting station.

Figs. 1 and 2 illustrate a container (formulation) 20 having a powder charge 19 containing lower part (female part) 22 and a closure part 21 after sealing under stress-free conditions. It is evident that an essentially uninterrupted surface is defined after the assembly of a lower part fitting part 24 with a closure part fitting part 23 on the outside of the capsule (the container). FIGS. 3a to 3u show various embodiments of the fit 18th It is evident that a smooth, essentially uninterrupted outer surface of the container 20 is fixed in the area of the fit 18 .

Fig. 4 illustrates in horizontal section the structure of a filling machine provided with a sealing station. In this case, a magazine 1 with a constantly vibrating conveyor chute or -rinne 2 is connected which transfers the container lower parts to a base feeding station 3, in which the lower parts pressed with upwardly oriented opening by means of a ram 3a in the lower part-holder 3 . The holders 5 are in turn attached to a turntable 4 . The container lower parts are then transferred to a series of timed steps, which are determined by the stepwise rotation of the turntable 4 to a filling station 6 in which each sub-part of a metered amount of a of a storage container 6 a supplied powdery, pasty or liquid filling material 19 receives.

The lower parts thus filled then move, likewise in successive, time-controlled steps, to a sealing station 7 , in which the closing parts supplied by means of vibration via a conveyor chute or trough 9 are transported from a closing part magazine 10 to a felt piece 12 a , moistened by the latter and then placed on the respective lower parts of the container. These operations are carried out by a star wheel 8 and a closure part holder 8 a . After the step-by-step conveying, which is again time-controlled, each closed container - in the present case in the form of a pharmaceutical dosage form capsule - is ejected from the lower part holder 5 on arrival at an ejection station 11 .

Fig. 5 is a partial sectional view of a sealing station. The closure parts 21 are located in the conveyor chute 9 , from which they are removed by means of negative pressure through the closure part holder 8 a and then transferred to the positioning and wetting unit 12 by means of a combined rotary movement and vertical movement. By means of the vertical movement of the holder 8 a , the closure part 21 is pressed onto the felt piece 12 a and thus impregnated with sealing liquid 13 . At the same time, the closure part 21 is aligned and wetted with the sealing liquid in its overlap area. The sealing liquid supplied from a container 14 is sucked up by capillary action into the felt piece 12 a , the liquid level in the container 14 being kept at a constant level by means of a dropper 15 and an overflow 16 . During the subsequent rotation of the holder 8 a in connection with a vertical movement, the closure part 21 is inserted into the sealing station 7 and pressed onto the lower container part 22 by means of a vertical movement of the holder 8 a . Obviously, the wetting can also be done in other ways. At the same time, the closure part 21 in the holder 8 a holding negative pressure is released. The holder 8 a now moves with rotary movement and vertical movement to the vibrating conveyor chute 9 to accommodate a new closure part.

The sealing machine described and the sealing station are new and are part of this invention. While pharmaceutical hard gelatin capsules are usually supplied to the sealing machine in the pre-closed state, the closing part 21 and the lower part 22 can be entered into separate magazines or storage containers and transported independently of one another to the sealing station 7 . The parts can also be wetted independently before closing.

The following examples are intended to explain the invention in more detail.

Example 1

The lip (fitting part according to FIG. 3a) of the closure part ( 21 ) of a container of the form according to FIG. 1, molded from natural wheat starch according to the conditions according to EP 84 300 940.8 (118 240), example 8 (water content: 12.7%) is pressed into a fine felt, which is impregnated with a sealing liquid of 70 vol .-% water and 30 vol .-% ethanol, 1.5 mm deep, so that the thin lip of this closure part is completely wetted. Then this closure part is assembled without tension with the adapted lower part of the container.

After 10 minutes, the container can no longer be opened. The same result is obtained if the container is before with a solid, pasty or liquid pharmaceutical Composition is filled. The filled containers are leakproof and leakproof.

Example 2

The procedure of Example 1 is repeated, but with an additional operation in which the container immediately (instantaneous) one of the following heat sources

• 1) air heated to 35 ° C, 3 min;
• 2) infrared radiation, 2.5 min;
• 3) ultrasonic energy, 2 s;

is exposed.

The container can then no longer be opened and is impermeable to liquids.

Example 3

The lip (according to FIG. 3e) of the closure part ( 21 ) of a gelatin capsule according to the invention of the form according to FIG. 1 produced according to the conditions according to EP 83 301 643.9 (090 600), example B-2 (water content: 14.6%) placed on a plate which carries a 1.0 mm high liquid film of a mixture of water and ethanol (80:20). The cap (the closure part) is then combined with the lower part of the container without deformation.

After a holding or dwell time of 15 min at room temperature the container can no longer be opened. At subsequent application of one of those mentioned in Example 2 Heat sources give you the shorter welding times specified there.

In no case did the container leave after the sealing was finished open without destruction.

Example 4

The procedures according to Examples 1, 2 and 3 are repeated, sealing fluids of the following Compositions are used:

Claims (15)

1. A method for filling and sealing containers with a non-locking fit, which have been produced by compression molding and preferably injection molding from natural starch or at least one other hydrophilic material or a mixture of compounds of this type, a container base and have a closure part and are preferably in the form of pharmaceutical (dosage form) capsules, characterized in that

• a) the contents are filled into a container of the specified type which is free of a snap lock,
• b) a sealing liquid with either the entire fit surface of the closure part, which in the closed state touches the (assigned) fit surface of the lower part of the container, or with an element of this fit surface of the closure part and / or with the entire fit surface of the lower part, which in the closed state of the Container touches the (assigned) mating surface of the closure part, or is brought into contact with an element of this mating surface of the lower part and
• c) then the lower part is joined together with the closure part to form the permanently or irrevocably closed container.

2. The method according to claim 1, characterized in that one as a natural strength is a naturally occurring one vegetable carbohydrate used, the main thing consists of amylose and amylopectin and preferably from potatoes, rice, tapioca or corn or from Rye, oats and / or wheat was obtained. 3. The method according to claim 1, characterized in that the "other hydrophilic materials" gelatin, vegetable Proteins, such as sunflower, soybean, cottonseed, Peanut and rapeseed proteins, blood proteins, Egg proteins, acylated proteins; water soluble Polysaccharides, such as alginates, carrageenans, Guar gum, agargar, gum arabic and related Gum (ghatti, karaya, tragacanth gum) and pectin, mean. 4. The method according to claim 1, characterized in that the "other hydrophilic materials" water-soluble derivatives of cellulose, for. B. alkyl celluloses, hydroxyalkyl celluloses and hydroxyalkyl alkyl celluloses, such as:
Methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxybutyl methyl cellulose, cellulose esters and hydroxyalkyl cellulose esters such as cellulose acetyl phthalate (CAP), hydroxypropyl methyl cellulose (HPMCP); Carboxyalkyl celluloses, carboxyalkylalkyl celluloses, carboxyalkyl cellulose esters such as carboxymethyl cellulose and their alkali metal salts; water-soluble synthetic polymers, such as polyacrylic acids and polyacrylic acid esters, polymethacrylic acids and polymethacrylic acid esters, polyvinyl acetates, polyvinyl alcohols, polyvinyl acetate phthalates (PVAP), polyvinylpyrrolidone, polycrotonic acids; phthalylated gelatin, gelatin succinate, cross-linked gelatin, shellac, water-soluble chemical derivatives of starch, cationic modified acrylates and methacrylates. 5. The method according to any one of claims 1 to 4, characterized characterized that in addition to natural strength and / or other hydrophilic materials Extenders, plasticizers and / or dyes are present are. 6. The method according to any one of claims 1 to 5, characterized characterized in that the strength and / or the other hydrophilic materials Containers have a water content of 10-20%, preferably 12-19% and in particular 14-18% on the weight of all the container wall constituting components.   7. The method according to any one of claims 1 to 6, characterized in that that the container base and the Allow the closure part to be put together without deformation. 8. The method according to any one of claims 1 to 7, characterized characterized in that aqueous sealants are used Solutions of sucrose, starch, mono-, oligo- and Polysaccharides, glycerin and other polyols, glycol, Polyethylene glycols and / or propylene glycols, per se known anionic, cationic or amphoteric surface-active Agents, gelatin, polyvinyl alcohols, water-soluble anionic or cationic acrylic polymers in a concentration of 0.5-10% by weight, preferably 1-4 wt .-%, based on the total weight the sealing liquid used. 9. The method according to any one of claims 1 to 7, characterized characterized in that as a sealing liquid a mixture of water and an alcohol in one Water / alcohol ratio of 95: 5 to 40:60, preferably about 80:20 to 60:40, preferably about 70:30, used. 10. The method according to claim 9, characterized in that an alcohol with 1-4 C atoms, preferably Ethanol, propanols and butanols, especially ethanol or isopropyl alcohol, preferably ethanol. 11. The method according to claim 1, characterized in that the closure point is heated after the closure, preferably with convection heat, electromagnetic Radiation of an appropriate frequency, preferably Microwaves or infrared radiation, or ultrasound energy.   12. The method according to any one of claims 1 to 11, characterized characterized in that the filling solid, pasty or is liquid. 13. The sealed according to claims 1 to 12 obtained Container. 14. Container with non-latching fit, manufactured by injection molding of natural strength or others hydrophilic materials or a mixture of compounds of this type, especially in the form of pharmaceutical Dosage form capsules with a container base and a closure part that is deformation-free can be put together for use in a Process according to claims 1 to 12. 15. Device for filling and closing pressure-molded containers in the form of pharmaceutical capsules, characterized by a lower part magazine ( 1 ), a conveyor slide or channel ( 2 ) connecting the magazine ( 1 ) with a lower part feed station ( 3 ), a device ( 3 a) for fixing the container lower parts in a lower part holder ( 5 ) attached to a rotary table ( 4 ), a filling station ( 6 ), a closing station ( 7 ), a closing part magazine ( 10 ), a transport slide or channel ( 9 ) for feeding the closure parts to closure part holders ( 8 a) and an ejection station ( 11 ) adjoining the closing station ( 7 ).