EP2046662A1

EP2046662A1 - Packaging comprising pharmaceutical forms

Info

Publication number: EP2046662A1
Application number: EP07765037A
Authority: EP
Inventors: Stefan Henke; Holger Peitz
Original assignee: Merck Patent GmbH
Current assignee: Merck Patent GmbH
Priority date: 2006-08-03
Filing date: 2007-07-04
Publication date: 2009-04-15
Also published as: AU2007280754B2; CA2659558A1; JP2009545343A; WO2008014862A1; US20090314664A1; RU2009107273A; KR20090036606A; RU2448026C2; MX2009001041A; CN101495385A; AU2007280754A1; ZA200901464B; BRPI0714619A2

Abstract

The invention relates to a packaging comprising solid pharmaceutical forms packed into a container (2) and in blisters (4).

Description

Pack containing pharmaceutical dosage forms

The invention relates to a pack comprising a container and blister-packaged solid pharmaceutical dosage forms, and a method for stabilizing solid pharmaceutical dosage forms by introducing the solid pharmaceutical dosage forms into blisters and moving the blisters into the container.

Under blister packaging hereinafter be understood from two firmly bonded together films containing cavities for receiving the solid to be packaged. Typically, blisters consist of a thermoformed plastic film (trough film) for receiving the solid, which after filling with a second film (cover film), which consists mostly of an aluminum and / or plastic film, firmly connected, d. H. is sealed. The packaged solids can be pressed against the blister by pressure on the trough film through the cover and removed individually. Blisters are therefore also called blister packs. If, due to the shape, size and / or strength of the solids contained, it is not possible to "press through" the covering film, the blisters can also be opened by slitting the covering film with a pointed object, eg with a fingernail. Blister "is not limited thereto but also includes special embodiments, such as. B. childproof modifications, such. For example, those in which two different opening operations must be performed, their processes should go beyond the child's thinking (as so-called "peel-push systems"), or embodiments in which the cover is not pierced before removing the solids contained but is withdrawn ,

Blisters are preferred primary packaging for solid pharmaceutical dosage forms. Advantages are that the dosage forms individually and thus without contamination of the remaining in sealed Cavities contained dosage forms can be removed individually, the dosage forms are separated from each other (whereby their interaction, such as abrasion or sticking are avoided).

Another important function of blistem is the protection of the pharmaceutical dosage forms contained therein from harmful environmental influences such as light, gases, in particular oxygen, and from moisture. In particular, the latter function is of particular importance, since many drugs are sensitive to moisture. Since blisters are usually placed in cartons that do not provide an effective barrier to moisture and gases, the key protection afforded by the blisters is in solid pharmaceutical dosage forms packaged in blisters (primary packaging) and cartons (secondary packaging).

However, the plastic films used for blisters provide only limited protection against externally penetrating gases and moisture. There are various plastic films such. As polyvinyl chloride (PVC), polyvinylidene chloride (PVDC) ₁ high density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, each having different material properties. By choosing a material with lower permeability to moisture or by using composite films of these materials such. B. PVC / PVDC, PVC / HDPE, optionally together with other polymers as a barrier layer, such as. As cycloolefin copolymer (COC), or special polyhalogenated polymers such as polychlorotrifluoroethylene (PCTFE) Aclar ^® , (PVC / PCTFE composite films, PP / COC (eg Polybar ^® ) PVC / COC / PVDC), the penetration of moisture, although to some extent diminished but not completely prevented. In addition to the choice of plastic, the material thickness, ie the film thickness, has a significant influence on the permeability of the blister. Thus, in addition to the selection of materials and the combination thereof to composite films by increasing the film thickness, the permeability to gases and moisture can be reduced. However, even these measures have only a limited effect and also do not lead to the desired extensive exclusion of moisture. Also disadvantageously result in a higher production cost, a higher material usage and difficulties in processing the films to Blistem and their recycling.

By using composite films which also contain metal foils, the permeability to moisture and gases can be significantly reduced again, but in this case there are particular difficulties in processing (thermoforming) and in recycling. When using composite films containing metal foils, the blisters are also no longer transparent, so that the customer can no longer see the pharmaceutical dosage forms contained therein, which is undesirable for safety and marketing reasons.

The problems described have the consequence that many moisture-sensitive drugs are not packed in blisters in regions with increased humidity, eg. In the tropics, exported and marketed.

To solve the problems described special blisters have been proposed which contain desiccants and thereby to keep the moisture away from the drug.

EP 466068 discloses a blister, wherein in each case a tablet cavity is connected to a cavity containing a desiccant. The provision of a desiccant per dosage form, such. As a tablet, however, is associated with high material and space consumption, packaging technically complex and expensive. US 4753352 discloses a blister wherein a plurality of tablet cavities are connected to a desiccant-containing cavity. Although this can reduce the packaging costs per pharmaceutical dosage form, the removal of only one pharmaceutical administration form from the blister then leads to the opening of the previously closed system, with the result that moisture can penetrate through the resulting opening. After exhaustion of the moisture absorption of the associated desiccant associated with this desiccant further pharmaceutical dosage forms are then no longer sufficiently protected against penetrating through the film and through the passages of the desiccant moisture. Furthermore, in both systems can not be ruled out that instead of the pharmaceutical dosage form, the desiccant is removed and taken, which is extremely questionable for safety reasons.

For the latter problem of accidental removal proposes EP 779872 A1, a reinforcement of the blisters in the desiccant cavities, which should prevent accidental removal of the desiccant by the user. However, this leads to an additional increase in the already increased by the introduction of desiccant production and cost.

While simple blisters often provide inadequate protection against moisture, desiccant-containing blisters are complicated in structure, difficult and therefore expensive to manufacture, can not be made on simple blister factories, take up more space due to the desiccant contained, and thus increase storage space requirements and / or have security issues. Furthermore, with desiccant-containing blisters also not always a sufficient protection against moisture can be ensured. It was an object of the present invention for pharmaceutical dosage forms to provide a simple packaging in which the pharmaceutical dosage forms are present in isolated form, in which a secure protection against moisture is ensured and which does not have the above-mentioned problems.

Surprisingly, the object could be achieved by initially introducing the pharmaceutical administration forms into a simple blister and subsequently placing them in a container in whose inner wall at least part of the channels at least one channel former is embedded together with at least one absorbent and firmly closed. The invention thus relates to a package comprising a resealable container, in the inner wall at least part of which at least one channel former is embedded together with at least one absorbent, and at least one blister containing one or more solid pharmaceutical dosage forms, wherein the / the blister in the container is / are included.

The container is intended for the storage of at least one blister. It can therefore have all spatial forms that fulfill this function, ie those which are suitable to receive at least one blister in itself. It is preferred that the spatial shape of the container is adapted to the dimensions of the blister. Should z. B. blisters are stored with a rectangular blank, it is preferred that the container has the same basic shape, ie that the container has the spatial shape of a cuboid, blisters should be stored with a round blank, it is preferred that the container is the spatial shape of a cylinder having. Likewise, according to the invention can be used as a container but also regardless of the blank of the blister any spatial form, as far as it is only suitable to receive the blister in itself. For example, a blister with round blank in a container with a cuboid spatial form or a blister with rectangular blank are stored in a container with cylindrical space shape.

Individual embodiments of the invention are shown in the figures. To identify the components of the embodiments shown in the figures, a uniform numbering is used, i. H. like numbers in the figures indicate the same components.

Figure 1 shows a rectangular container with a blister with rectangular blank. The container comprises walls (2) whose inwardly directed sides contain at least part of at least one channel former together with at least one absorbent, has a lid (1) as closure and is provided with an (optional) opening aid (3). The blister (4) contains cavities (5) for receiving the solid pharmaceutical dosage forms.

FIG. 2 shows, like FIG. 1, a cuboid container and a blister, but with different dimensions of the container and a blister with a round blank.

FIG. 3 shows a container with a cylindrical spatial form. The round wall (2) contains at least part of the channel surface in the inwardly directed side together with at least one absorbent and is provided with a matching circular lid (1) and (optional) fulfillment aid (3). The blister (4) is strip-shaped, contains oval cavities (5) for receiving the solid dosage forms and provided with a tear-off aid (6) along which the blisters can be divided.

The container is resealable. Reclosable means that the container can be repeatedly, ie at least once, preferably several times, more preferably at least as often opened and closed again, as it corresponds to the number of solid pharmaceutical dosage forms, packed in blister, in the container should be included. The container is closed so tightly after each opening and closing process, that penetration of moisture and gases into the container interior is effectively prevented.

Opening and closing of the container is carried out by a container adapted, serves closing closure. Not limited to a lock. It can be used all types of closures, as long as they ensure even after repeated opening and closing of the container that gases and / or moisture in the closed state can not penetrate into the container interior. The container may have one or more closures. In the case of cuboid containers, basically any of the rectangular surfaces can be designed as a closure. Figure 4 shows an embodiment of a cuboid container with two closures (1).

According to one embodiment of the invention, lids (1) are used as the closure. Examples of lids are screw caps, caps which are slipped over the top of the vessels, or inserted into the interior of the vessel. For spatial forms that have corners, such. As cuboids, the corners of the opening and the matching lid can also be slightly rounded to increase the tightness of the container to gases and moisture.

According to a preferred embodiment, the container has a cuboid spatial shape, rounded corners (7) and is well stackable (see Figure 5).

The absorbents and channel formers contained in the container can either be contained directly in the inner wall (s) of the polymer forming the container or applied as a layer to the inner wall (s) of the container made of polymers. Likewise, absorbents and channel formers can be embedded in an inlay, which is introduced as an insert into the container, so that at least a part of the inner walls of the container are thereby lined. Under Innenwandung / s is the inwardly facing surface of the wall / walls of the container understood, so the area / n of the container, which are in contact with the present contained in blisters solid pharmaceutical dosage forms standing / stand.

As materials for the property in question come polymers. Polymers which can be used in admixture with absorbent and channel former are in particular thermoplastics such as e.g. Polyolefins such as polyethylene and / or polypropylenes, polyisoprenes, polybutadienes, polybutenes, polysiloxanes, polyamides, ethylene-vinyl acetate copolymers, ethylene-methacrylate copolymers, polystyrenes, polyesters, polyanhydrides, polyacrylate nitriles, polysulfonates, polyester amides, polyacrylate esters, propylene maleic anhydride, polyethylene Maleic anhydride, polyethylene urethanes, polyethylene-ethylvinyl alcohols, polyethylene-nylon and / or polyurethanes. The walls provided on their inner surface with absorbent and channeling agent have a polymer content of 10-90% by weight, based on the total weight of the mixture of polymer, channeling agent and absorption substances.

Basically, any type of desiccant, d. H. moisture-binding binder, be included. Three groups of desiccants can be considered:

The first group contains chemicals that form hydrates with water. Examples of such chemicals are anhydrous salts which tend to absorb water or moisture to form a stable hydrate. The moisture is bound and their release is prevented by a chemical reaction.

The second group of desiccants contains substances that are reactive. The substances react with water or moisture by forming a new substance. The newly formed materials are usually stable at low temperatures, which is reversible only with the use of high energy. This type of desiccant is mainly used for drying Solvents and as a water-absorbing material in polymers that need to remain in a moisture-reduced state itself used.

The third group of desiccants binds the moisture by adsorption of phosphorus. The desiccant contains particles with capillaries into which the moisture is drawn. The pore size of the capillaries and their density in the drying agent determine the absorption properties. Examples of such desiccants are molecular sieves, silica gels, certain synthetic polymers, such as e.g. Such as those used in baby diapers and starches. Desiccants of the third group are preferably contained in the container, since they are largely inert and insoluble in water. Particular preference is given to molecular sieves having a pore size of from 3 to 15 angstroms and / or silica gels having a pore size of 24 angstroms.

Suitable channeling agents are hydrophilic substances such. As polyglycols, ethylvinyl, glycerol, polyvinyl alcohols, polyvinylpyrrolidone, vinylpyrrolidone, N-methylpyrrolidone, polysaccharides, saccharides and / or sugar alcohols. As polyglycols, polyethylene glycol and / or polypropylene glycol are preferred. As saccharides, e.g. Glucose, mannose, galactose and / or fructose. Suitable sugar alcohols are e.g. Mannitol, sorbitol, hexitol, dulcitol, xylitol, ribitol and / or erythrol. By polysaccharides are meant e.g. Dextrins and / or hydrolyzed starch.

In the inner walls equipped with absorbents and channel formers, the channel formers, based on the total weight of the mixture of polymer, channel former and absorbent, can have a proportion of 10 to 40% by weight.

Absorbents and channel formers are embedded in the inner wall (s) of the container over part of the area or over the whole area. Partial area means that at least a part of the total forming the Innenwandung / s Surface of the container contains absorbent and channel former. Whole-area means that the entire, the inner walls forming surface of the container contains absorbent and channel former. According to an advantageous embodiment, based on the entire inner surface of the container, absorbents and channel-forming agents are contained in at least 10%, preferably in at least 50%, particularly preferably in at least 90% of the inner walls.

Containers of polymers containing absorbent and channel former and which are suitable as a container for the package according to the invention, are known in the art and z. As described in WO 97/32663 A1, EP 1000873 A2 and WO 03/086900 A1, EP 1421991 A1. Containers which can be used in the pack according to the invention are commercially available and are described, for example, by Capitol Specialty Plastics Inc., 2039 McMillan Street Auburn, Alabama, USA, under the trademark Activ-Vial or by Süd Chemie, Ostenrieder Str 15, 85368 Moosburg, Germany, under the brand name 2 AP Multipolymer.

Preferably and advantageously, the blisters can be made of simple plastic films which have a high permeability to water vapor. After introduction of the blister into the container and closure of the same they are then in a dry environment, which is ensured by the drying effect of the located in the walls of the container absorbent. At higher humidity in the interiors of the (the solid pharmaceutical dosage forms containing) blisters against the interior of the container (which is ensured by the desiccant) this diffuses through the plastic film of the blister through into the container interior, where they are absorbed by the desiccant contained in the Behältniswandungen becomes. If the pharmaceutical dosage forms contained in the blisters have a higher humidity than the surrounding interior spaces of the blisters, moisture diffuses out the pharmaceutical dosage forms out into the interiors of the blister and then further, as described, through the plastic film of the blister through into the container interior. With increased humidity of the pharmaceutical dosage forms relative to the container interior, drying of the solid pharmaceutical dosage forms occurs even after their packaging.

Compared to commercially packaged in cartons blisters it comes in the package according to the invention to a reversal of the diffusion direction of moisture that i in conventional packaging for blisters such as cartons. d. R. from outside to inside, d. H. in the direction of the pharmaceutical dosage form, in the direction from inside to outside, d. H. from the cavity of the blister and also out of the pharmaceutical dosage form out. This results in the packaging according to the invention even after production and packaging of the pharmaceutical dosage forms in blisters a drying of the pharmaceutical dosage form, which advantageously leads to a further increase in storage stability, especially in pharmaceutical dosage forms with sensitive ingredients.

Due to the drying in the pack according to the invention after filling of the pharmaceutical dosage forms into the blisters, the pharmaceutical dosage forms can also be provided more cost-effectively, since after their preparation necessary drying times can be omitted or shortened.

All plastic films which can be processed into blisters in corresponding systems, in particular thermoforming systems, and which have a certain water vapor permeability, can be used to produce blisters suitable for the pack according to the invention. Examples of plastic films suitable for producing blisters are polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), high density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, Cycloolefin copolymer (COC), special polyhalogenated polymers such as polychlorotrifluoroethylene (PCTFE) Aclar ^® , as well as composite films of these materials such. PVC / PVDC, PVCVHDPE ₁ PVC / PCTFE, PP / COC (Polybar ^® ) PVC / COC / PVDC, especially suitable are PVC, PVDC, HDPE, PP, PET as well as composite foils of these, especially suitable PVC, PP, and PET. The plastic films can be used as a trough film and / or as a cover film. Preferably, at least the trough film consists of a plastic film.

Preferably and advantageously, plastic films of small thickness are used to produce the blisters. Because with a reduction in the material thickness of the films also reduces their diffusion resistance, so that the described stabilization of the pharmaceutical dosage form by deprivation of moisture during storage can occur even faster. The plastic films used as a trough film usually have thicknesses of 10 to 500 .mu.m, preferably 15 to 300 .mu.m, more preferably 15 to 100 .mu.m, very particularly preferably 15 to 50 are used.

High permeability to water vapor and low film thickness allow the use of inexpensive plastic films such. As PVC, PP, and PET at a thickness of 250 microns have a water vapor permeability (WDP) according to DIN 53122 of about 3.5, 0.84 and 5.4 g / cm ² 24h. , In addition to savings in material costs, such films can also be processed and filled well on conventional thermoforming systems, resulting in additional cost advantages.

Usually aluminum foil is used for the sealing of blisters, which has a low water permeability. In the package of the invention, a low water permeability is not required, so that other materials can be used to seal the blister. This allows the use of plastic films as a cover film, with films of the same material as the Muldenfolie can be used. Such single-material packages are particularly advantageous since they can be recycled without prior separation of trough film and cover, which is particularly desirable for environmental reasons. When using plastic films as cover film contained in the cavities of the bladder water vapor can be removed through the cover, which advantageously increases the rate of drying of the pharmaceutical dosage forms contained in the blister. If, in addition, a plastic film with very low material thickness is used, this results, in addition to reduced material costs, a further increase in the drying speed and easier removal of the solid pharmaceutical administration form contained in the blister, since this can then be penetrated more easily.

According to an advantageous embodiment, each cavity of the blister containing a solid pharmaceutical dosage form contains at least one hole. The hole (s) preferably have a diameter of <1 mm, they facilitate the exchange of gases and moisture from the cavities of the blisters in the interior of the container of the package according to the invention, so that the drying speed is significantly increased. The holes also make it possible to use plastic films with high gas and moisture permeability and increased film thickness for the blisters, without the stabilization resulting from the drying being reduced. The invention therefore also relates to the pack according to the invention, which is characterized in that the blister (s) contained in the pack has at least one hole in each cavity containing a solid pharmaceutical dosage form.

If several holes are included, these are preferably in the form of a series of small cuts / punched holes, ie perforations which, inter alia, facilitate tearing along the resulting line. Subject of the The invention is therefore also packaging, which is characterized in that in each cavity in each case a plurality of holes are included as a perforation.

Most preferably, the perforations are microperforations, d. H. Perforations with a diameter between 0.25 and 0.05 mm, which can be punched into the films. The invention therefore furthermore relates to a package which is characterized in that the perforation contained per cavity is a microperforation.

The holes / perforations may be contained in the trough and / or the cover of the blister and be introduced both before and after the filling of the blister in the films. The introduction of the holes / perforations can according to the prior art known methods such. B. by mechanical punching or by burning done by means of laser light. The introduction of the holes / perforations can be made in the plastic films prior to their processing into blisters, during their processing into blisters and also after the production and fulfillment of the blisters.

If pre-perforated / pre-perforated films are used, preferably only the cover film is perforated / perforated. This allows easy processing of the trough film in conventional thermoforming equipment and protects the pharmaceutical dosage forms after their introduction into the wells from contamination in the thermoforming system. The filled trough film can then be easily sealed with the cover, which is preferably perforated, more preferably microperforated. FIG. 3 shows a blister (4) which is provided with perforations (8). If the pharmaceutical dosage forms are removed by puncturing the covering film, the perforations are preferably introduced in such a way that, when the depression foil is pressed onto the perforation, the covering foil can be torn open along the perforations and the dosage forms can be removed in a simple manner. The invention therefore further relates to the pack according to the invention, which is characterized in that Hole, the holes, perforation or micro perforation is introduced respectively in the cover sheet is / are.

Pharmaceutical dosage forms that may be included in the pack are all solid pharmaceutical dosage forms that are in the test state at room temperature and z. B. are provided for oral, anal or vaginal administration. Included are all solid pharmaceutical dosage forms that are provided after removal from the container for direct administration, such as. As tablets, dragees, hard capsules, granules, pellets, powders, suppositories, but also those which must be converted before administration still in the administrable form, such. As dry juices, for example in the form of powders, which must be converted before administration in solution. Preferably, the pharmaceutical dosage form is a tablet, a dragee, a hard capsule, a granule, a suppository, a pellet or a powder. Hard capsules have shells without plasticizer additives, are divisible into the upper and lower part and consist for example of gelatin or starch.

The invention also provides a process for producing the pack, which is characterized in that the solid pharmaceutical dosage forms are placed in a blister and sealed and the sealed blister is then introduced into a container consisting of a tightly closable container, in the inner wall / en at least part of the channel at least one channel former is embedded together with at least one absorbent.

Pharmaceutical dosage form (s) is hereinbefore and hereinafter understood to mean various types of technical administration known for the administration of drugs to humans or animals. The term pharmaceutical dosage form is thus independent of a particular legal status and not limited to drugs as ingredients can different substances such. As drugs, nutritional supplements and / or functional ingredients. Examples of pharmaceutical dosage forms in the context of the present invention can be present as medicaments and dietary supplements.

Surprisingly, the process according to the invention also makes it possible to provide marketable products to solid pharmaceutical administration forms which have hitherto been unsuitable for commercialization according to the prior art since they are not sufficiently storage-stable. After transfer of the dosage form into the container, the dosage form is withdrawn continuously and over a long period of time from the absorption medium contained in the inner wall (s) of the container. The removal of water takes place over a large area and under mild conditions and thus leads to the stabilization of the solid pharmaceutical dosage form during its storage.

The invention therefore also relates to a method for increasing the shelf life of solid pharmaceutical dosage forms, which is characterized in that this is placed in a blister and sealed and the sealed blister is then placed in a container which consists of a tightly closed container, in the inner wall / s at least part of the channel at least one channel former is embedded together with at least one absorbent is.

The stabilizing effect of the pack according to the invention is based on the influence of the container on the solid pharmaceutical dosage form contained in the blister, which can be made available in this way in a storage-stable manner. Achieving the effect of the invention thus requires that the solid pharmaceutical dosage form contained in blisters is contained in the container, the pharmaceutical dosage form, blister and container are thus present together as a pack. The pack according to the invention has a stabilizing effect on all solid pharmaceutical dosage forms whose active ingredient (s) and / or adjuvant (s) are sensitive to moisture. Examples of moisture-sensitive active ingredients are many pharmaceutical agents such as hormones or proteins, vitamins, cells, such as probiotic cultures.

The pack according to the invention preferably contains solid pharmaceutical dosage forms which contain moisture-sensitive active substances and / or moisture-sensitive auxiliaries or excipient combinations. A moisture sensitive adjuvant combination is z. B. the combination of an organic acid, such as. As citric acid, with carbonate, such as. As sodium bicarbonate or potassium bicarbonate, as used in effervescent tablets.

The solid pharmaceutical dosage form contained in the pack according to the invention may also contain customary auxiliaries and additives, depending on the embodiment. The choice of auxiliaries and / or additives also depends on the food legislation of the country in which the solid pharmaceutical dosage form contained in the package is to be used. Suitable auxiliaries and / or additives are, for example, for tablets, multilayer tablets, dragees, hard capsules, granules, pellet preparations and / or powders, starch (eg corn starch), talc, microcrystalline cellulose, lactose, fumed silica, polyvinylpyrrolidone and / or cellulose powder used , Carbohydrates, such as, for example, mannitol, sorbitol, xylitol, glucose, sucrose, fructose, maltose, dextrose, maltodextrin and / or kaolin and / or cellulose derivatives, such as, for example, methylcellulose, hydroxypropylcellulose and / or hydroxypropylmethylcellulose, can be used as further constituents as binders and / or release agents / or calcium carbonate, calcium, magnesium and / or glycerol stearate. Furthermore, the solid pharmaceutical dosage form contained in the pack can also be colored, flavored and / or Flavorings, as well as lubricants, antioxidants and / or stabilizers. The content of these basic substances depends on the one hand on the desired content of the substances to be administered such as drugs, nutritional supplements, functional ingredients on the other hand criteria that determine the mechanical-physical properties of the oral dosage form, such as hardness, compressibility, size, color and / or Shape.

The preparation of the solid pharmaceutical dosage form contained in the pack can be carried out by various methods known to the person skilled in the art. These methods are e.g. from H. Sucker, P. Fuchs, P. Speiser, "Pharmaceutical Technology", Stuttgart 1978 or K.H. Bauer, K.H. Frömming, C. Führer, "Pharmaceutical Technology", Stuttgart 1986. They are hereby incorporated by reference and are thus part of the disclosure.

The examples, without being limited thereto, illustrate the invention.

Example 1 :

3-layered tablet analogous to EP 931 543 A1 containing probiotic bacteria

production:

Mixtures of 3% by weight of bacterial preparation (containing Lactobacillus gasseri, Bifidobacterium bifidum, Bifidobacterium longum), 10.5% by weight of inulin, 8.6% by weight of calcium phosphate, 5.7% by weight of cellulose, 2.3 Wt .-% excipients (disintegrants, release agents) (1st layer), minerals, trace elements, dyes, disintegrants, release agents, cellulose (2nd layer) and vitamins, trace elements, disintegrants, release agents and cellulose (3rd layer) (percentages in each case based on total tablet weight), are successively pressed on a 3-layer tablet press (rotary) from E. Hata to form an oblong-shaped 3-layer tablet measuring 18 mm x 8 mm. The resulting tablets are then provided with a film coating (from aqueous solution containing hydroxypropyl methylcellulose, hydroxypropyl cellulose and a release agent), the coating was, based on the weight of the core, 5 wt .-%, corresponding to 11 mg / cm ² tablet surface. Coated 3-layer tablets are obtained, each weighing 1050 mg.

Storage and testing:

The stability of the film-coated tablets is checked in shelf life studies. For this purpose, film tablets either in PVC-aluminum blister (packaging A) or in PVC-aluminum blisters and this in a packaging, in the inner wall of a channel former is embedded together with an absorbent, (Packing B) introduced, and at 40 ° C. / 75% RH stored. After predetermined times is outsourced and the respectively contained microorganism number after the Kochschen Plate casting method determined by counting. The results are summarized in Table 1 (average of three batches)

Table 1

Example 2:

production:

Mixtures of 10% by weight of nicorandil and auxiliaries (fillers, disintegrants and release agents) are pressed on a tablet press into a round tablet. Tablets weighing 100 mg each are obtained.

Claims

claims

A package comprising a resealable container, in the inner wall of which at least part of the channel at least one channel former is embedded together with at least one absorbent, and at least one blister containing one or more solid pharmaceutical dosage forms, wherein the / the blister is / are included in the container ,

2. Pack according to claim 1, characterized in that the container has a cuboid basic shape.

3. A package according to claim 1 or 2, characterized in that the container contains as absorbent a desiccant, which binds moisture by physical adsorption.

4. A package according to claim 3, characterized in that the desiccant is a molecular sieve or silica gel.

A package according to claim 1, characterized in that the trough and / or cover sheet of the blister (s) comprised of polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), high density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, cycloolefin copolymer (COC), polychlorotrifluoroethylene (PCTFE), or composite films of these materials such as PVC / PVDC, PVC / HDPE, PVC / PCTFE, PP / COC, PVC / COC / PVDC. ,

6. A package according to claim 5, characterized in that consist as a trough and / or cover made of PVC, PP or PET.

A package according to claim 1, characterized in that the blister (s) contained in the package is contained in at least one cavity in each cavity containing a solid pharmaceutical dosage form.

8. A package according to claim 7, characterized in that each cavity more holes are included as a perforation.

9. A package according to claim 8, characterized in that the perforation is a micro perforation.

10. A package according to one or more of claims 7 to 9, characterized in that the hole, the holes, perforation or micro perforation Jeweiis is introduced in the Abdeckfoiie / are.

A package according to claim 1, characterized in that the solid pharmaceutical dosage form (s) contained in the blister (s) contained herein are tablets, dragees, capsules, granules, suppositories, pellets and / or powders.

12. A method for producing the package according to one or more of claims 1 to 11, characterized in that the solid pharmaceutical dosage forms are placed in a blister and sealed and the sealed blister is then introduced into a container consisting of a tightly closed container, in the inner wall / s at least part of the channel at least a channel former is embedded together with at least one absorbent.

13. A method for increasing the shelf life of solid pharmaceutical dosage forms, characterized in that this is placed in a blister and sealed and the sealed blister is then placed in a container consisting of a tightly closed container, in the Innenwandung / s at least part of the area at least a channel former is embedded together with at least one absorbent.