RU2448026C2 - Package with pharmaceutical preparations - Google Patents

Abstract

FIELD: transport, package.

SUBSTANCE: invention relates to package containing container and solid pharmaceutical preparations packed in bubble packs. Said container allows reclosure. Inner wall comprises, at least, one agent to form at least one channel on, at least, a part of surface, and adsorbent. Bubble pack contains one or several pharmaceutical preparations and is kept in aforesaid container.

EFFECT: simple deign, higher waterproof quality.

13 cl, 5 dwg

Description

The invention relates to a package containing a container and solid pharmaceutical dosage forms packed in blister packs, as well as to a method for stabilizing solid pharmaceutical dosage forms by placing solid pharmaceutical dosage forms in blister packs and placing blister packs in the container.

Blister packaging further refers to packaging from two films firmly connected to each other, which contain cavities for accommodating solids to be packed. Typically, blister packs consist of a synthetic film formed by deep drawing (packaging / bottom, having a film-shaped film) to place solids in it, which, after filling, are firmly connected, i.e. sealed with a second film (cover film), which in most cases consists of aluminum foil and / or synthetic film. Packed solids by pressing on the packaging film can be individually squeezed out and removed through the cover film from the blister pack. Therefore, blister packs are called “pushable packs”. If, due to the shape, size and / or hardness of the contained solids, “extrusion” through the cover film is not possible, the blister packs can be opened by cutting a gap in the cover film with a sharp object, such as a nail file. However, the term “blister pack” is not limited to this only, but also includes special structural forms, such as, for example, modifications safe for children, such as, for example, in which two different opening actions must be taken, the mechanism of which should go beyond the framework of children's consciousness (the so-called "Peel - Push - System"), or constructive forms in which the coating film for removing the contained solids should not be pressed through, but removed.

Blister packs are the preferred primary packaging agent for solid pharmaceutical dosage forms. The advantages are that the dosage forms can be removed individually and thereby without contamination of the rest contained in the sealed cavities of the dosage forms, as dosage forms are contained separately from each other (whereby their effect on each other, such as, for example, abrasion or sticking, is essentially prevented).

Another important function of blister packs is to protect the pharmaceutical dosage forms contained in them from the negative effects of the external environment, such as light, gases, especially oxygen, as well as moisture. First of all, the function named by the latter has special meaning, since many medicines are sensitive to moisture. Because usually blister packs are placed in folding cartons that do not constitute a significant barrier to moisture and gases, the principal protective effect for packaged in blister packs (primary packaging) and folding cartons (secondary packaging) of solid pharmaceutical dosage forms is formed by blister packs .

Synthetic films used for blister packs provide only limited protection against gases and moisture penetrating from the outside. Various synthetic films are available, such as, for example, polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), high density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, each of which has different material properties. By choosing a material with low moisture permeability or by using multilayer films of these materials, such as, for example, PVC / PVDC, PVC / HDPE, if necessary also together with other polymers as a barrier layer, such as, for example, cycloolefin copolymer (SOS), or special polyhalogenated polymers such as Aclar® polychlorotrifluoroethylene (PCTFE), (PVC / PCTFE multilayer films, PP / SOS (e.g. Polybar®) PVC / COC / PVDC) moisture penetration, although it can be reduced to a certain extent however cannot be completely prevented.

In addition to choosing a synthetic film, the thickness of the material, i.e. film thickness has a significant effect on the permeability of the blister pack. Thus, in addition to the choice of materials, as well as their combinations in multilayer films, the penetration of gases and moisture can be prevented by increasing the thickness of the film. However, these measures have a limited effect and therefore do not lead to the desired significant exclusion of moisture. Also at the expense of increased production costs, increased material consumption, as well as difficulties in processing films into blister packs and in their recycling.

Through the use of multilayer films, which also contain metal foil, the penetration of moisture and gases can be significantly reduced again, however, in this case there are particular difficulties in processing (deep drawing), as well as in secondary processing. In the case of using multilayer films containing metal foil, the blister packs are no longer transparent so that the consumer can no longer see the pharmaceutical dosage forms contained therein, which is not desirable for safety and marketing reasons.

The described problems entail that many moisture-sensitive drugs are exported and marketed in regions with high humidity, for example, in the tropics, not in blister packs.

To solve the described problem, special blister packs were proposed that contain a drying agent (dehumidifier), and thus should protect medicines from moisture.

EP 466068 describes a blister pack in which each tablet cavity is connected to a cavity containing a drying agent. However, giving each dosage form, for example a tablet, a drying agent is associated with a high consumption of material and the use of space is difficult and expensive from the technical point of view of packaging technology.

US 4,753,352 describes a blister pack in which several tablet cavities are connected to a cavity containing a drying agent. Although thereby the packaging costs of the pharmaceutical dosage form can be reduced, the removal of only one dosage form from the blister pack leads to the opening of a closed system that entails the penetration of moisture through the opening. After the absorption of moisture of the drying agent thus connected is exhausted, the other pharmaceutical dosage forms connected to this drying agent are no longer sufficiently protected from penetrating through the film, as well as through the connecting channels of the drying agent of moisture. In addition, in both systems it is possible that instead of a pharmaceutical dosage form, a drying agent will be removed and accepted, which is quite dangerous for security reasons.

For this latter problem of random extraction, EP 779872 A1 proposes hardening (reinforcing) the blister pack in the region of the cavity containing the drying agent, which should prevent the user from accidentally removing the drying agent. However, this leads to an additional increase in the already increased due to the placement of the drying agent production and material costs.

While simple blister packs often provide insufficient protection against moisture, blister packs containing a drying agent are complex, complicated, and therefore expensive to manufacture, cannot be manufactured in production workshops for simple blister packs, due to the drying contained in them the agent has more space, and thereby increase the need for storage space and / or are associated with security problems. In addition, blister packs containing a drying agent also may not always provide sufficient protection against moisture.

The objective of the invention was the development of simple pharmaceutical packaging for pharmaceutical dosage forms, in which the pharmaceutical dosage forms are arranged in pieces, which provide reliable protection against moisture and the above problems are absent.

Unexpectedly, this problem was solved due to the fact that the pharmaceutical dosage forms were first placed in a simple blister pack, and then it was placed in a container, in the inner wall (s) of which at least one channel-forming agent is introduced together with at least one absorbent, and tightly closed. Thus, the object of the invention is a package containing a container made with the possibility of repeated closure, in the inner wall (s) of which at least one channel forming agent is introduced along with at least one absorbent and at least one absorbent at least one blister pack containing one or more pharmaceutical dosage forms, wherein the blister pack (s) are / are contained in the container.

A container is provided for storing at least one blister pack. It can have any spatial forms that carry out this function, i.e. those that are suitable for containing at least one blister pack. It is preferable that the spatial shape of the container is consistent with the dimensions of the blister pack. In the case of storing, for example, rectangular shaped blister packs, it is preferred that the container has the same basic shape, i.e. The container has the spatial shape of a rectangular parallelepiped. In the case of storing a blister pack of round shape, it is preferable that the container has a spatial cylinder shape. In the same way, according to the invention, any spatial form can also be used as a container, regardless of the style of the blister pack, as long as it is suitable for accommodating a blister pack. For example, a blister pack of a round style can be stored in a container with a spatial shape of a rectangular parallelepiped or a blister pack of a rectangular style can be stored in a container with a cylindrical spatial shape.

Particular constructive forms of the invention are presented in the figures. To indicate the components of the structural forms shown in the figures, a single numbering is used, i.e. the same numbers indicate in the figures in each case the same components.

Figure 1 shows a container in the form of a rectangular parallelepiped of rectangular cross section. The container contains walls (2), the inward-facing sides of which contain at least one channel forming agent along with at least one absorbent on at least a portion of the surface, has a cover (1) as a closing element and is equipped with an (optional) opening auxiliary (3). The blister pack contains cavities (5) for placement of solid pharmaceutical dosage forms.

Figure 2 shows a container and a blister pack made in the form of a rectangular parallelepiped, however with different dimensions of the container and a blister pack of a round style.

Figure 3 shows a container with a cylindrical spatial shape. The round wall (2) contains at least one channel forming agent on the inward side of the at least part of the surface together with at least one absorbent material and is provided with a suitable circle-shaped lid (1) and an (optional) opening aid ( 3). The blister pack is made in the form of a strip (tape), contains oval cavities (5) for placement of solid dosage forms and is equipped with peeling aid (6) along which the blister pack can be divided.

The container is made with the possibility of re-closure. The possibility of re-closure means that the container is re-closed, i.e. at least once, preferably repeatedly, particularly preferably can be opened and closed again as often as the number of solid pharmaceutical dosage forms to be contained in a blister pack. After each opening and closing, the container is closed so tight that the penetration of moisture and gases into the container is effectively prevented.

Opening and closing of the container takes place with the help of a hermetically sealed closing element, not limited to only one closing element. All types of closing elements can be used which, after repeated openings and closures of the container, ensure that gases and / or moisture cannot penetrate into the container. In the case of a container made in the form of a rectangular box, essentially any of the rectangular surfaces can be made in the form of a closing element. Figure 4 shows the structural form of a container made in the form of a rectangular box with two locking elements (1).

In one of the structural forms of the invention, a cover (1) is used as a closing element. Examples of caps are screw locks, caps that are adjacent to the top of the containers or inserted into the containers. In the case of spatial forms having corners, for example a rectangular parallelepiped, the corners of the hole and a suitable lid can be rounded off in order to increase the impermeability of the container with respect to gases and moisture.

According to a preferred structural form, the container has a spatial shape in the form of a rectangular parallelepiped, rounded corners (7) and is well stacked in a stack (see figure 5).

The absorbent and channel forming agent contained in the container can be applied together either directly into the inner wall (s) of the polymer forming the container, or as a layer on the inner wall (s) of the polymer container. Similarly, the absorbent and channel forming agent can be introduced into the liner, which is inserted into the container as a replaceable module, so that at least part of the inner wall is covered. By inner wall is meant the inwardly facing surface of the wall (s) of the container, i.e. the surface (s) of the container, which is in contact with the solid pharmaceutical forms contained therein in blister packs.

Polymers may be used as materials for the container. The polymers that can be used in admixture with the absorbent and channel forming agent are primarily thermoplastics, such as, for example, polyolefins, such as polyethylene and / or polypropylene, polyisoprene, polybutadiene, polybutene, polyorganosiloxanes, polyamides, ethylene vinyl acetate copolymers, ethylene methacryl copolymers , polystyrenes, polyesters, polyanhydrides, polyacrylate nitriles, polysulfonates, polyeteramides, polyacrylates, propylene maleic hydrides, polyethylene urethanes, polyethylene ethyl vinyl alcohol, poly Lennylon and / or polyurethanes. Equipped with an absorbent and channel forming agent on their inner surfaces, the walls have a polymer content with respect to the total weight of the polymer mixture forming the agent channels and absorbents from 10 to 90 weight percent.

Essentially, any type of drying agent (silica gel) can be used as absorbent. Three groups of drying agents can be used:

The first group includes chemicals that form hydrates with water. Examples of such chemicals are anhydrous salts, which tend to absorb water or moisture and form a stable hydrate. Moisture binds and its release is prevented through a chemical reaction.

The second group of drying agents includes reactive substances. Substances react with water or moisture, as a result of which they form a new substance. Typically, newly formed materials are stable at low temperatures and are reversible only when high energy is applied.

This type of drying agent is mainly used to dry solvents and as a water-absorbing material with polymers, which themselves must remain in a state of reduced moisture.

A third group of drying agents binds moisture through physical adsorption. The drying agent contains particles with small capillaries into which moisture can be absorbed. About this, the pore sizes of the capillaries, as well as their density in the drying agent, determine the absorption properties. Examples of such drying agents are molecular sieves, silica gels, certain synthetic polymers, such as, for example, used in baby diapers, and starches. Preferably, the drying agents of the third group are used in the tank, as they are substantially inert and insoluble in water. Particularly preferred are molecular sieves with pore sizes of 3 to 15 angstroms and / or silica gels with pore sizes of 24 angstroms.

Hydrophilic substances such as, for example, polyglycols, ethylvinyl vinyl alcohol, glycerin, polyvinyl alcohol, polyvinyl pyrrolidone, vinyl pyrrolidone, N-methyl pyrrolodone, polysaccharides, saccharides and / or polypropylene glycol can be used as channel forming agents. As saccharides, for example, glucose, mannose, galactose and / fructose can be used. As a multi-valued alcohol, for example, mannitol, sorbitol, hexitol, dylsitol, xylene, ribitol and / or erythol can be used. Polysaccharides mean, for example, dextrins and / or hydrolyzed starches.

In the inner walls provided with drying agents and channel forming agents, the contents of the channel forming agents can comprise from 10 to 40 weight percent, based on the total weight of the polymer, channel forming agent and drying agent mixture.

A drying agent and channel forming agent are introduced into the inner wall (s) of the container on the entire surface or on a part of the surface. On a surface part, it means that at least a part of the aggregate surface forming the inner wall (s) comprises a drying agent and a channel forming agent. On the entire surface means that the entire surface of the container forming the inner walls contains a drying agent and a channel forming agent. According to a preferred embodiment, the drying agent and the channel forming agent are contained in at least 10%, preferably at least 50%, particularly preferably at least 90% of the inner walls.

Polymer containers containing drying agents and channel forming agents and suitable as packaging containers according to the invention are known in the art and are described, for example, in WO 97/32663 A1, EP 1000873 A2 and WO 03/086900 A1, EP 1421991 A1 . Containers that can be used in the packaging of the invention are commercially available and are available, for example, from Capitol Specially Plastics Inc., 2039 McMillan Street Auburn, Alabama, USA under the trademark Activ-Vial or from Sued Chemie, Ostenrieder Str. 15, 85368 Moosburg, Deutschland.

Preferably and predominantly blister packs can be made of simple synthetic films that have high permeability to water vapor. After the blister packs are placed in the container and the latter is closed, they are in a dry environment, which is ensured by the drying effect of the drying agent located in the walls of the container. With high moisture in the internal cavities (containing solid pharmaceutical dosage forms) of the blister pack compared to the interior of the container (which is provided by a drying agent), it diffuses through the synthetic film of the blister pack through the inside of the container, where it is absorbed by the drying agent contained in the walls of the container. When the moisture content of the pharmaceutical dosage forms contained in the blister packs is higher than the inner space surrounding the blister packs, moisture diffuses from the pharmaceutical dosage forms into the inner space of the blister pack and then, as already described, through the synthetic film of the blister pack into the inside of the container. Thus, with increased moisture of the pharmaceutical dosage forms relative to the inside of the container, this leads to the draining of the solid pharmaceutical dosage forms even after their packaging.

Compared to the blister packs packaged in folding cartons in the packaging according to the invention, there is a change in the direction of moisture diffusion, which in commercial packs for blister packs, such as, for example, folding cartons, usually occurs from the outside to the inside, those. in the direction of pharmaceutical dosage forms, in the direction from the inside out, i.e. from the cavity of a blister pack and from a pharmaceutical dosage form. By this means, in the packaging according to the invention, also after the production and packaging of the pharmaceutical dosage forms in blister packs, the drying of the pharmaceutical dosage forms occurs, which advantageously leads, in particular, with pharmaceutical dosage forms with sensitive constituents, to further increase storage stability.

Due to the drying occurring in the packages according to the invention, after filling the pharmaceutical dosage forms into blister packs, pharmaceutical dosage forms can also be made cheaper because the necessary drying after their manufacture disappears or its time is reduced.

For the manufacture of blister packs suitable for packaging according to the invention, all synthetic films can be used that can be processed in the respective plants, especially in deep drawing plants, into blister packs and which have a corresponding water vapor permeability. Examples of synthetic films suitable for the manufacture of blister packs are polyvinyl chloride (PVC), polyvinylide chloride (PVDC), high density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, cycloolefin copolymer (CO), special polyhalogenated polymers such such as Aclar® polychlorotrifluoroethylene (PCTFE), as well as multilayer films of these materials such as PVC / PVDC, PVC / HDPE, PVC / PCTFE, PP / COC (Polybar®) PVC / COC / PVDC, especially suitable PVC, PVDC, HDPE , PP, PET, as well as multilayer films of them, especially suitable are PVC, PP and PET. Synthetic films can be used as packaging films and / or coating films. Preferably, at least the packaging captive consists of a synthetic film.

Preferably and mainly for the manufacture of blister packs using synthetic films with a small thickness. Because as the material thickness decreases, their diffusion resistance also decreases so that the described stabilization of pharmaceutical dosage forms by removing moisture during storage can occur even faster. Synthetic films commonly used as packaging films have a thickness of from 10 to 500 μm, preferably from 15 to 300 μm, especially from 15 to 50 μm.

The high permeability to water vapor and the small film thickness allows the use of low-cost synthetic films, such as, for example, PVC, PP and PET, which have a water vapor permeability in accordance with DIN 53122 of about 3.5, 0.84 with a thickness of 250 μm, or 5.4 g / cm ² 24 hours. In addition to saving on the cost of material, films of this kind can be well processed and filled in conventional deep drawing plants, which creates additional advantages in production costs.

Typically, aluminum foil is used to seal blister packs, which has low water permeability. In the packaging according to the invention, low water permeability is not required, so that other materials can also be used to seal blister packs. This allows the use of synthetic films as a coating film, while films of the same material as for the packaging film can also be used. Packages made of one material of this kind are particularly preferred since they can be reused without prior separation of the packaging film and the coating film, which is especially desirable for environmental reasons. When using synthetic films as a coating film, water vapor contained in the cavities of the blister pack can also be taken through the coating film, which advantageously increases the drying rate of the dosage forms contained in the blister pack. If a synthetic film with a very small material thickness is used, in addition to a reduced material consumption, a further increase in the drying speed is achieved, as well as an easier extraction of the solid pharmaceutical dosage forms contained in the blister pack, as they can then be easier pressed through.

In an advantageous structural form, each cavity containing solid pharmaceutical dosage forms has at least one opening. The hole / s have preferably a diameter of <1 mm, they facilitate the exchange of gases and moisture from the cavities of the blister pack into the interior of the container so that the drying speed is significantly increased. The holes allow the use of synthetic films for blister packs with high gas and moisture permeability and increased film thickness without reducing the stabilization obtained by drying. Therefore, an object of the invention is also a package according to the invention, which is characterized in that the blister pack (s) contained in the package (s) have (at least) a hole in each cavity containing solid pharmaceutical dosage forms.

If there are several holes, they are arranged in the form of a series of small cuts / punched holes, i.e. perforations, which, among other things, facilitate tearing along the resulting line Therefore, an object of the invention is also a package, which is characterized in that in each cavity there are several holes made in the form of perforation.

A particularly preferred perforation is microperforation, i.e. holes with a corresponding diameter between 0.25 and 0.05 mm, which can be carved into the films. Therefore, a further object of the invention is a package, which is characterized in that the perforation in each cavity is microperforation.

Holes / perforations may be contained in the packaging and / or coating film of the blister pack and may be applied to the films both before and after filling the blister packs. The application of holes / perforations can occur in a manner known per se from the prior art, such as, for example, mechanical punching or burning by means of a laser beam. Holes / perforations in synthetic films can occur before they are processed into blister packs, during processing into blister packs, and also after the manufacture and filling of blister packs.

When using films with pre-made holes / perforations, only a cover film with pre-made holes / perforations is preferred. This allows for trouble-free packaging film processing in conventional deep drawing units and protects pharmaceutical dosage forms after they are placed in the forms from contamination in the deep drawing unit. The filled packaging film can then be seamlessly sealed with a coating film, which is preferably perforated, particularly preferably microperforated. Figure 3 shows a blister pack (4), which is provided with perforations (8). If the extraction of the pharmaceutical dosage forms occurs by forcing the coating film, the perforation is preferably applied in such a way that, when pressure is applied to the lower film, the coating film breaks along the perforation and the dosage forms can be removed in a simple way. Therefore, a further object of the invention is a package according to the invention, which is characterized in that the hole, holes, perforation or microperforation is made (s) respectively in the coating film.

Pharmaceutical dosage forms that may be contained in a package are any solid pharmaceutical dosage forms that are in a solid state of aggregation at room temperature and, for example, are intended for oral, anal and vaginal use. All solid pharmaceutical dosage forms are covered, which, after removal from the container, are intended for direct use, such as, for example, tablets, dragees, capsules, granules, pellets, suppositories, however, those which must be converted into ready-to-use forms before use , such as, for example, dry juices, for example in the form of powders, which must be converted into a solution before use. Preferably, the pharmaceutical dosage form is a tablet, dragee, hard-shell capsule, granule, suppository, pellet or powder. Hard-shell capsules have shells without emollients, are divisible into the upper and lower parts, and consist, for example, of gelatin or starch.

A subject of the invention is also a method for manufacturing a package, characterized in that the solid pharmaceutical dosage forms are placed in a blister pack and sealed, and then the sealed blister pack is placed in a container which can be tightly closed in the inner wall (s) of which at least on a surface portion of at least one channel forming agent together with at least one absorbent.

Under the dosage form (s) as previously, and further understand various dosage forms, as they are known for the use of drugs for humans or animals. Thus, the expression "pharmaceutical dosage form" is independent of a certain legal status and is in no way limited to drugs, and the contents may contain various substances, such as, for example, drugs, food additives and / or functional ingredients.

Unexpectedly, the method according to the invention also allows the preparation of ready-to-sell products of solid pharmaceutical forms, which until now, according to the prior art, were unsuitable for this, because they are not stable enough during storage. After the dosage forms are placed in a container, water is withdrawn from the dosage forms continuously and over a long period of time by means of a drying agent contained in the inner wall (s) of the container. The selection of water occurs on a large surface and in favorable conditions and leads to stabilization of the solid pharmaceutical dosage form during storage.

Therefore, an object of the invention is a method for increasing the storage stability of solid pharmaceutical dosage forms, characterized in that they are placed in a blister pack and sealed, and then the sealed blister pack is placed in a container that can be tightly closed in the inner wall (s) of which at least one channel forming agent is introduced on at least a portion of the surface together with at least one absorbent.

The stabilizing effect of the package according to the invention is based on the effect of the container on the solid pharmaceutical dosage forms contained in the blister pack, which can thereby be stable during storage. The exposure according to the invention therefore requires that the solid pharmaceutical form contained in the blister pack is contained in a container, i.e. the pharmaceutical dosage form, blister pack, and container together are a pack.

The package according to the invention has a stabilizing effect on all solid pharmaceutical dosage forms, the active agent (s) and auxiliary agents which are sensitive to moisture. Examples of moisture-sensitive active agents are many pharmaceutical agents, such as hormones or proteins, vitamins, cells, such as, for example, probiotic structures.

Preferably, the package according to the invention contains solid pharmaceutical dosage forms that contain moisture-sensitive active agents and / or moisture-sensitive auxiliary agents, or combinations of auxiliary agents. The moisture-sensitive combination of auxiliary agents is, for example, a combination of an organic acid, such as, for example, citric acid, and a carbonate, such as, for example, sodium hydrogen carbonate or potassium hydrogen carbonate, in the form in which they find use as effervescent tablets.

In addition, the solid pharmaceutical dosage form contained in the package according to the invention may contain conventional auxiliary and additional agents. The choice of auxiliary and / or additional agents also depends on the sanitary requirements of the country in which the solid pharmaceutical dosage form contained in the package is to be used. As an auxiliary and / or additional agent, tablets, multilayer tablets, hard-shell capsules, granules, suppositories, pellets and / or powders are used for starch (e.g., corn starch), talc, microcrystalline cellulose, lactose, highly dispersed silicon dioxide, polyvinylpyrrolidone and / or cellulose powder. As other constituents, carbohydrates, such as, for example, mannitol, sorbitol, xylitol, glucose, sucrose, fructose, maltose, dextrose, maltodextin and / or kaolin and / or cellulose derivatives, may be contained as an astringent and / or separating agent, such such as methyl cellulose, hydroxypropyl cellulose and / or hydroxypropyl methyl cellulose and / or calcium carbonate, calcium stearate, magnesium stearate and / or glycyrine stearate. In addition, the solid pharmaceutical dosage form contained in the package also contains colorants, flavors and / or flavors, as well as giving (for example, tablets) a slippery substance, antioxidants and / or stabilizers. The content of these basic substances is determined, on the one hand, by the desired content of dispensed (consumed) drugs, food additives, functional ingredients, and on the other hand, by criteria that determine the mechanical and physical properties of oral dosage forms, such as, for example, hardness, compression, size, color and / or shape.

The preparation of the solid pharmaceutical dosage forms contained in the packaging may be carried out by any method known to the skilled person. These methods are known, for example, from G. Zucker, P. Fuchs, P. Speiser “Pharmaceutical Technology” (H. Sucker, P. Fuchs, P. Speiser, “Pharmazeutische Technologie”, Stuttgart, 1986), or from K.X .Bauer, K.X. Froming, C. Führer "Pharmaceutical Technology" (K.N. Bauer, K.N. Froeming, C. Fuehrer, "Pharmazeutische Technologie", Stuttgart, 1986). By this, they are incorporated by reference and are thereby part of the description.

Examples illustrate the invention without limiting it.

Example 1

Three-layered tablet taxed of probiotic bacteria described in EP 931534 A1

Manufacture:

A mixture of 3 weight percent of a bacterial preparation (containing Lactobacillius gasseri, Bifidobacterim bifidum, Bifidobacterium longum), 10.5 weight percent of inulin, 8.6 weight percent of calcium phosphate, 5.7 weight percent of cellulose, 2.3 weight percent of excipients (explosive composition, release agent) (first layer) containing minerals, trace elements, dyes, explosive composition, release agent, cellulose (second layer), as well as vitamins, trace elements, explosive composition, release agent and cellulose (third layer) (p percentage set data are given in each case relative to the total weight of the tablet) are pressed to each other in the press for the manufacture of three-layer tablets (Runlaufer from E. Hata) having an elongated shape in the three-layer tablet size of 18 mm × 8 mm. Then, the resulting tablet is provided with a film coating (from an aqueous solution containing hydroxypropyl methylcellulose, hydroxypropyl cellulose and a release agent), the coating being 5% by weight relative to the core weight, corresponding to 11 mg / cm ² . Coated three-layer tablets were obtained, each weighing 1050 mg.

Storage and verification:

The stability of the coated tablets was tested in the study for durability. For this purpose, coated tablets were placed either in a blister pack of PVC-aluminum (packaging agent A) or in a package of PVC aluminum, into the inner wall of which a channel-forming agent was introduced together with an absorbent (packaging agent B) and stored at 40 ° C / 75% rF. After a certain time, they were removed and the quantity of each of the contained microorganisms was determined by counting according to the Kochschen - Plattenguss method. The results are shown in table 1 (average of three measurements)

Table 1 Controlled parameter Start Storage conditions 40 ° C / 75% rF 13 weeks 26 weeks Packing A Probiotic cultures [KBE] 7.1 × 10 ⁷ <1.0 × 10 ³ - Packing B Probiotic cultures [KBE] 7.1 × 10 ⁷ 5.5 × 10 ⁷ 6.7 × 10 ⁷

Example 2

Manufacture:

A mixture of 10 weight percent nicorandil and excipients (fillers, explosive composition and release agent) was pressed out on a press to make tablets into a round tablet. Tablets were obtained, each weighing 100 mg.

Claims (13)

1. A package containing a container made with the possibility of re-closure, in the inner wall (s) of which at least one channel-forming agent is introduced along with at least one absorbent material, as well as at least one blister pack a package containing one or more pharmaceutical dosage forms, wherein the blister pack (s) are / are contained in a container. 2. Packaging according to claim 1, characterized in that the container has a basic shape made in the form of a rectangular parallelepiped. 3. The packaging according to claim 1 or 2, characterized in that the container as an absorbent contains a drying agent that binds moisture through physical adsorption. 4. Packaging according to claim 3, characterized in that the absorbent is a molecular sieve or silica gel. 5. Packaging according to claim 1, characterized in that the packaging and / or coating film of the blister pack (s) contained therein (s) consists of (s) polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), high density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, cycloolefin copolymer (CO), polychlorotrifluoroethylene (PCTFE) or from multilayer films of these materials, such as PVC / PVDC, PVC / HDPE, PVC / PCTFE, PP / SOS, PVC / COC / PVDC. 6. Packaging according to claim 5, characterized in that the packaging and / or coating film consists of PVC, PP or PET. 7. The package according to claim 1, characterized in that the blister pack (s) contained therein (s) has (at) at least one opening in each cavity containing solid pharmaceutical dosage forms. 8. The packaging according to claim 7, characterized in that in each cavity there are several holes made in the form of perforation. 9. Packaging according to claim 8, characterized in that the perforation is microperforation. 10. Packaging according to one of claims 7 to 9, characterized in that the hole (s), perforation or microperforation is made (s) respectively in the coating film. 11. Packaging according to claim 1, characterized in that the solid pharmaceutical dosage forms contained in the blister pack (s) contained therein are tablets, dragees, capsules, granules, suppositories, pellets and / or powders. 12. A method of manufacturing a package according to one of claims 1 to 11, characterized in that the solid pharmaceutical dosage forms are placed in a blister pack and sealed, and then the sealed blister pack is placed in a container made with the possibility of tight re-closure in the inner wall (- ki) of which at least one channel forming agent is introduced on at least a portion of the surface together with at least one absorbent. 13. A method of increasing the stability of solid pharmaceutical dosage forms during storage, characterized in that they are placed in a blister pack and sealed, and then the sealed blister pack is placed in a container made with the possibility of tight re-closure, in the inner wall (s) of which is inserted at least on a surface part of at least one channel forming agent together with at least one absorbent.

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