JP2009545343A - Pack containing pharmaceutical preparation - Google Patents

Abstract

A method for stabilizing a solid pharmaceutical formulation is provided.
A package containing a solid pharmaceutical preparation loaded in a container (2) and a blister (4) is used.
[Selection] Figure 3

Description

  The present invention relates to a pack comprising a solid pharmaceutical formulation loaded into a container and a blister pack and a method of stabilizing a solid pharmaceutical formulation by placing the solid pharmaceutical formulation in the blister pack and placing the blister pack in the container.

The blister pack described below is used to mean a package comprising two sheets, films or foils that are firmly bonded together and contain cavities for containing the solids to be loaded. Blister packs are usually firmly bonded, ie heat-sealed, after filling to a second sheet, film or foil (cover sheet, film or foil) made of aluminum foil and / or plastic sheet or film Usually, it consists of a plastic sheet or film (cavity sheet or film) thermoformed to contain the solid. The packaged solid can be individually removed from the blister pack by pressing the cover sheet, film or foil with pressure against the cavity sheet, film or foil. Blister packs are therefore also known as push-through packs. If “pushing out” the cover sheet, film or foil is not possible due to the shape, size and / or strength of the contained solid, the blister pack will also use sharp objects, eg, finger It can be opened by opening the cover sheet, film or foil with the nail. However, the term “blister pack” is not limited to this, but is intended to be in a special embodiment, such as an improvement that cannot be opened by a child, for example, a sequence intended to exceed the child's intellectual ability. One that requires two different opening operations (eg a so-called “peel-push system”), or a cover sheet, film or foil that is not opened, but instead peeled before removing the contained solids It includes forms.
Blister packs are the preferred primary packaging means for solid pharmaceutical formulations. The advantage is that the formulations can be removed individually, so that the formulations are separated from each other without further incorporation of the other formulation contained in the sealed cavity (interactions such as wear or sticking). It basically means prevention).
An important function of the blister pack is also the protection of the pharmaceutical formulation contained therein against harmful environmental influences such as light, gas, especially oxygen and moisture. The last mentioned function is particularly important because many drugs are vulnerable to moisture. Blister packs are usually housed in non-barrier folding boxes that are effective against moisture and gas, so in the case of solid pharmaceutical preparations packaged in blister packs (primary packaging means) or folding boxes (secondary packaging means). An important protective effect is caused by the blister pack.

However, the plastic sheet or film used in the blister pack provides only limited protection against gas and moisture entering from the outside. There are various plastic sheets or films, such as polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), high density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, but the material properties of each Are different. Selection of materials with a relatively low permeability to moisture or composite sheets or films made from these materials, for example PVC / PVDC (PVC / HDPE), optionally with another polymer as a barrier layer, for example Cycloolefin copolymer (COC), or special polyhalogenated polymers such as polychlorotrifluoroethylene (PCTFE) Aclar® (PVC / PCTFE, PP / COC (e.g. Polybar®) PVC / COC Use, which may be with (/ PVDC composite sheet or film), allows for some reduction in moisture ingress, but does not completely prevent it.
Besides the choice of plastic, the thickness of the material, i.e. the thickness of the sheet, film or foil, also has an important influence on the permeability of the blister pack. Therefore, in addition to selecting the material from which the composite sheet or film is obtained and the combination thereof, the permeability of gas and moisture can be reduced by increasing the thickness of the sheet, film or foil. However, even these standards have only a limited effect and do not provide the desired substantial elimination of moisture. This is disadvantageous because of the increased complexity of production, the increased use of materials, the difficulty of converting sheets, films or foils into blister packs and their reuse.
The use of a composite sheet or film containing a metal foil makes it possible again to reduce the water and gas permeability again, but in this case certain problems arise during processing (thermoforming). With the use of composite sheets or films containing metal foil, blister packs are no longer transparent, meaning that consumers can no longer see the pharmaceutical formulation contained therein, for safety and marketing reasons Not desirable.
The problem described has the result that many moisture-sensitive drugs are not loaded into blister packs in exports and sales in areas with high atmospheric humidity, such as the tropics.
In order to solve the problems described, special blister packs have been proposed which contain desiccants and consequently are intended to protect the drug from moisture.

EP 466068 discloses a blister pack in which, in each case, the tablet cavity is connected to a cavity containing a desiccant. However, the supply of desiccant for each formulation, for example a tablet, is complicated and expensive from the point of view of packaging technology, in connection with the consumption of materials and the large use space.
US 4753352 discloses a blister pack in which a plurality of tablet cavities are connected to a cavity containing a desiccant. This makes it possible to reduce the packaging complexity of each pharmaceutical formulation, but opens up a previously closed system by removing only one pharmaceutical formulation from the blister pack, resulting in Moisture can enter through the open openings. After the moisture absorption of the desiccant connected to it is exhausted, other pharmaceutical formulations connected to this desiccant are no longer sufficiently protected against ingress moisture by the sheet or film and by the desiccant connection channel. . Furthermore, in any system, it cannot be excluded that the desiccant is taken out and taken in place of the pharmaceutical preparation, which is extremely important for safety reasons.
Regarding the problem of unintentional intake mentioned at the end, EP 779872 A1 proposes the reinforcement of blister packs in the area of desiccant cavities intended to prevent unintentional intake of desiccant by the user. Yes. However, this adds to the complexity and cost of manufacturing that would otherwise increase due to the introduction of the desiccant.
Simple blister packs often provide insufficient protection against moisture, but desiccant-containing blister packs have a complex structure, are difficult and therefore expensive to manufacture, and production for simple blister packs Storage requirements are increased and / or plagued by safety issues because they cannot be manufactured on-site and take up more space for the desiccant they contain. Furthermore, likewise, sufficient protection against moisture is not always ensured by a desiccant-containing blister pack.

WO 97/32663 A1 WO 03/086900 A1 EP 931 543 A1 EP 1421991 A1 EP 1000873 A2

H. Sucker, P. Fuchs, P. Speiser, "Pharmazeutische Technologie" [Pharmaceutical Technology], Stuttgart 1978 K.H. Bauer, K.H. Froemming, C. Fuehrer, "Pharmazeutische Technologie" [Pharmaceutical Technology], Stuttgart 1986

  The object of the present invention was to provide a simple packaging of pharmaceutical preparations, where the pharmaceutical preparations exist in isolated form, ensuring reliable protection against moisture and not suffering from the above-mentioned problems.

  Surprisingly, the pharmaceutical preparation is first placed in a simple blister pack, and then the latter is placed on one or more inner walls with at least one channel former together with at least one absorbent and at least one of the regions. The object was achieved by placing it in a container that was incorporated into the part and tightly sealed. Accordingly, the present invention provides a resealable container and one or more solid pharmaceutical formulations wherein at least one channel forming portion is incorporated in at least a portion of the region along with at least one absorbent on one or more inner walls. And a pack in which one or more blister packs are contained in a container.

FIG. 1 is a view showing a rectangular parallelepiped container containing a blister pack having a rectangular shape. FIG. 2 is a view showing a rectangular parallelepiped container and a blister pack as shown in FIG. 1, but the dimensions of the container are different and the blister pack has a circular shape. FIG. 3 is a view showing a container having a cylindrical spatial shape. FIG. 4 is a diagram showing an embodiment of a rectangular parallelepiped container having two closures (1). FIG. 5 is a view showing a container having a rectangular parallelepiped spatial shape, rounded corners (7), and can be stacked well.

The container is intended for storage of at least one blister pack. It can therefore have any spatial shape that fulfills this function. That is, it can be suitable for housing at least one blister pack. A spatial shape of the container that matches the dimensions of the blister pack is preferred. For example, if it is intended to store a blister pack having a rectangular shape, a container having the same basic shape, that is, a container having a rectangular parallelepiped spatial shape is preferred, and a blister pack having a circular shape is stored. Where intended, containers having a cylindrical spatial shape are preferred. However, it is equally possible according to the present invention to use any desired spatial shape as a container, regardless of the shape of the blister pack, as long as it is only suitable for housing the blister pack. For example, a blister pack having a circular shape can also be stored in a container having a rectangular spatial shape, or a blister pack having a rectangular shape can also be stored in a container having a cylindrical spatial shape. You can also
Individual embodiments of the invention are shown in the figures. The same numbers are used to indicate the components of the embodiment shown in the figure. That is, in any case, the same numeral in the figure indicates the same component.
FIG. 1 is a view showing a rectangular parallelepiped container containing a blister pack having a rectangular shape. The container has a wall (2). The inward facing side, together with at least one absorbent, has at least one channel forming part in at least part of the region, has a lid (1) as a closure, and (optional) an opening aid (3) Yes. The blister pack (4) contains a cavity (5) containing a solid pharmaceutical formulation.
FIG. 2 is a view showing a rectangular parallelepiped container and a blister pack as shown in FIG. 1, but the dimensions of the container are different and the blister pack has a circular shape.
FIG. 3 is a view showing a container having a cylindrical spatial shape. The circular wall (2) includes at least one channel forming part with at least one absorbent on the inward facing side in at least part of the region, and is fitted with a matching circular lid (1) and (optional) An auxiliary part (3) is provided. The blister pack (4) has a belt-like design, contains an elliptical cavity (5) containing a solid formulation, is provided with a cutting aid (6), and the blisters can be divided along it.

The container can be resealed. Resealable is at least enough to correspond to the number of solid pharmaceutical formulations loaded into the blister pack, which is intended to be repeated, ie at least once, preferably several times, particularly preferably contained in the container. Often means that it can be opened and resealed. Since the container is tightly sealed after each opening and sealing operation, moisture and gas can be effectively prevented from entering the container.
The container is opened and closed by a tightly closed closure adapted to the container. It is not limited to one closure. All types of closures can be used as long as it is ensured that no gas and / or moisture can enter the interior of the closed container even after repeated opening and closing of the container. The container can have one or more closures. In the case of a cuboid container, each of the rectangular surfaces can basically be designed as a closure. FIG. 4 is a diagram showing an embodiment of a rectangular parallelepiped container having two closures (1).
According to an embodiment of the present invention, the lid (1) is used as a closure. An example of a lid is a threaded closure where the cap is folded over the top rim of the container or introduced into the interior of the container. In the case of a spatial shape with corners, for example a cuboid, the opening and the corner of the fitted lid should be slightly rounded to enhance the sealing of the container against gas and moisture.
According to a preferred embodiment, the container has a rectangular parallelepiped spatial shape with rounded corners (7) and can be stacked nicely (see FIG. 5).
The absorbent and the channel forming part contained in the container may be jointly present directly on one or more inner walls of the polymer forming the container, or applied as a layer on one or more inner walls of the polymer container. May be. The absorbent and the channel forming part may likewise be incorporated into an inlay introduced into the container as an insert, so that at least a part of the inner wall of the container is lined with it.
The one or more inner walls are one or more of the inwardly facing surfaces of the one or more walls of the container, i.e. one of the containers in contact with the solid pharmaceutical formulation contained therein loaded in the blister pack Used to mean multiple surfaces.

A suitable material for the container is a polymer. Polymers that can be used as a mixture of absorbent and channel former are in particular thermoplastics, for example polyolefins such as polyethylene and / or polypropylene, polyisoprene, polybutadiene, polybutene, polysiloxane, polyamide, ethylene-vinyl acetate. Copolymer, ethylene-methacrylate copolymer, polystyrene, polyester, polyanhydride, polyacrylate nitrile, polysulfonate, polyester-amide, polyacrylate ester, propylene-maleic anhydride, polyethylene-maleic anhydride, polyethylene-urethane, polyethylene- Ethyl vinyl alcohol, polyethylene-nylon and / or polyurethane. The wall with the absorbent and channel former on the inner surface has a polymer content of 10-90% by weight, based on the total weight of the polymer, channel former and absorbent mixture.
Absorbents that may be present are in principle all types of desiccants, ie binders that bind moisture. Three groups of desiccants are considered:
The first group includes chemicals that form hydrates with water. An example of this type of chemical is an anhydrous salt that tends to absorb water or moisture and form a stable hydrate in the process. It binds moisture and its release is prevented by chemical reaction.
The second group of desiccants contains substances that are reactive. Substances react with water or moisture by forming new substances. Newly formed materials are usually stable at low temperatures, but are reversible only by high energy consumption. This type of desiccant is used primarily as a water-absorbing material in order to dry the solvent and in the case of polymers that themselves must remain in a low moisture state.
A third group of desiccants binds moisture by physical adsorption. The desiccant contains particles with fine capillaries that absorb moisture. The capillary pore size and its density in the desiccant determine the absorption characteristics. Examples of this type of desiccant are molecular sieves, silica gels, certain synthetic polymers such as those used for diapers, starch. The desiccant from the third group is preferably contained in the container because it is substantially inert and water insoluble. Here, molecular sieves with a pore size of 3 to 15 Å and / or silica gel with a pore size of 24 Å are particularly preferred.

Considered channel formers are hydrophilic substances such as polyglycol, ethyl vinyl alcohol, glycerol, polyvinyl alcohol, polyvinyl pyrrolidone, vinyl pyrrolidone, N-methyl pyrrolidone, polysaccharides, saccharides and / or sugar alcohols. Preferred polyglycols are polyethylene glycol and / or polypropylene glycol. Saccharides that can be used are, for example, glucose, mannose, galactose and / or fructose. Suitable sugar alcohols are, for example, mannitol, sorbitol, hexitol, dulcitol, xylitol, ribitol and / or erythrol. Polysaccharide is used, for example, to mean dextrin and / or hydrolyzed starch.
In the inner wall comprising the absorbent and the channel forming part, the proportion of the channel forming part may be 10-40% by weight based on the total weight of the mixture of polymer, forming part and absorbent.
The absorbent and the channel forming part are incorporated into one or more inner walls of the container in part of the region or in the whole region. A part of the region means that at least a part of the entire region of the container forming one or more inner walls is provided with an absorbent and a channel forming part. The whole area means that the whole area of the container forming the inner wall is provided with the absorbent and the channel forming part. According to an advantageous embodiment, the absorbent and the channel former are present in at least 10%, preferably at least 50%, particularly preferably at least 90% of the inner wall, based on the total internal surface area of the container.
Containers made from polymers comprising an absorbent and a channel forming part and suitable as containers for the packs of the present invention are known in the prior art, for example WO 97/32663 A1, EP 1000873 A2, WO 03/086900 A1, EP 1421991 A1. Containers that can be used in the packs of the present invention are commercially available, for example, under the trade name Activ-Vial, from Capitol Specialty Plastics Inc., 2039 Macmillan Street Auburn, Alabama, USA or under the trade name 2 AP Multipolymer, Sued Chemie, Ostenriedel Str. 15, 85368 Sold by Mosburg, Germany.
The blister pack is preferably and advantageously made from a simple plastic sheet or film that is highly permeable to water vapor. After placing the blister pack in the container and sealing it, it is placed in a dry environment ensured by the drying effect of the absorbent on the container wall. If the moisture content inside the blister pack (containing a solid pharmaceutical formulation) is relatively high compared to the inside of the container (as ensured by the desiccant), the container passes through the plastic sheet or film of the blister pack And is absorbed by the desiccant present on the container wall. If the pharmaceutical formulation contained in the blister has a higher moisture content than the interior of the blister that surrounds it, the moisture diffuses from the pharmaceutical formulation into the interior of the blister and then as described, the plastic sheet of the blister pack Or it diffuses through the film and into the container. If the water content of the pharmaceutical preparation is high compared to the inside of the container, drying of the solid pharmaceutical preparation occurs even after its packaging.

Compared to commercial blister packs packaged in a folding box, from the inside, i.e. from the cavity of the blister pack and from the pharmaceutical formulation to the outside, conventional secondary for blister packs like folding boxes In packaging, a reversal of the direction of moisture diffusion, which occurs normally from the outside to the inside, ie in the direction of the pharmaceutical formulation, occurs in the pack of the invention. As a result, drying of the pharmaceutical formulation occurs in the pack of the present invention even after manufacture and packaging of the pharmaceutical formulation in a blister pack, and advantageously provides increased shelf life, especially for pharmaceutical formulations with sensitive ingredients. It is done.
Due to the drying that takes place in the packs of the present invention after the pharmaceutical formulation has been dispensed into the blister packs, the pharmaceutical formulation can be made less expensive because the drying time required after their manufacture can be omitted or shortened. Can be provided.
All plastic sheets or films that can be converted into blister packs in corresponding plants, in particular thermoforming plants, and have a certain water vapor permeability are used for the production of blister packs that are suitable for the packs of the invention. Is appropriate to. Examples of plastic sheets and films that are suitable for the manufacture of blister packs are polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), high density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, Cycloolefin copolymers (COC), special polyhalogenated polymers such as polychlorotrifluoroethylene (PCTFE) Aclar®, composite sheets or films made from these materials, such as PVC / PVDC, PVC / HDPE, PVC / PCTFE, PP / COC (Polybar®) PVC / COC / PVDC, PVC, PVDC, HDPE, PP, PET, composite sheets or films made from these are particularly suitable, especially Appropriate PVC, PP and PET are particularly suitable. Plastic sheets or films can be used as cavity sheets or films and / or cover sheets or films. The cavity sheet or film is preferably made of at least a plastic sheet or film.
For the production of blister packs, preferably and advantageously a thin plastic sheet or film is used. This is because the decrease in the material thickness of the sheet or film is accompanied by a decrease in its diffusion resistance, so that the described stabilization of the pharmaceutical formulation is more due to the removal of moisture during storage. It can happen quickly. The thickness of the plastic sheet or film used as the cavity sheet or film is usually 10 to 500 μm, preferably 15 to 300 μm, particularly preferably 15 to 100 μm, very particularly preferably 15 to 50.

High water vapor permeability and low sheet or film thickness is an inexpensive plastic sheet or film, for example, a water vapor permeability (WVP) according to DIN 53122 at a thickness of 250 μm of about 3.5, 0.84, 5.4 g / cm ² 24 h Allows the use of PVC, PP and PET respectively. In addition to material cost savings, this type of sheet or film can also be processed and successfully filled in conventional thermoforming plants, adding cost advantages.
An aluminum foil with low water permeability is usually used to seal the blister pack. The pack of the present invention does not require low water permeability, meaning that other materials can be used to seal the blister pack. This allows the use of plastic sheets or films as cover sheets or films, and sheets or films made from the same material as the cavity sheets or films can also be used. This type of single material packaging is particularly advantageous because it allows the cavity sheet or film and the cover sheet or film to be recycled without prior separation, and is particularly desirable for environmental reasons. With the use of a plastic sheet or film as a cover sheet or film, water vapor present in the cavities of the blister pack can also be removed through the cover sheet or film, advantageously drying the pharmaceutical formulation contained in the blister pack Increase speed. In addition, if plastic sheets or films with very thin material thickness are used, this can be more easily pushed out besides reducing the material usage, thus increasing the drying rate and containing in blister packs Easier removal of the solid pharmaceutical formulation occurs.
According to an advantageous embodiment, each cavity of a blister pack containing a solid pharmaceutical formulation has at least one hole. The diameter of the single hole / multiple holes is preferably <1 mm, which simplifies the exchange of gas and moisture from the blister pack cavity inside the pack container of the present invention, and significantly increases the drying rate. means. The holes also allow an increase in sheet or film thickness used in high gas and moisture permeable plastic sheets or films and blister packs without reducing the stabilization that occurs due to drying. The present invention therefore relates to a pack according to the invention, characterized in that the blister pack or packs contained in the pack have at least one hole in each cavity containing a solid pharmaceutical formulation.

If there are multiple holes, they are preferably in the form of small cuts / perforations, i.e. rows of perforations, and in particular, easy to peel along the line formation. The present invention therefore relates to a pack characterized in that there are a plurality of holes as perforations in each cavity.
The perforations are particularly preferably microperforations, i.e. holes each having a diameter of 0.25 to 0.05 mm, which can be perforated in a sheet or film. Therefore, the present invention further relates to a pack characterized in that the perforations present in each cavity are microperforations.
The holes / perforations may be present in the cavity sheet or film and / or cover sheet or film of the blister pack and may be introduced into the sheet or film before or after filling the blister. Holes / perforations can be introduced by methods known from the prior art, for example by mechanically drilling holes or by baking with laser light. The holes / perforations can be introduced into the plastic sheet or film prior to its conversion into a blister pack, during its conversion into a blister pack, and after production filling of the blister pack.
Where a pre-perforated / pre-perforated sheet or film is used, it is preferred that only the sheet or film be perforated / perforated. This allows for trouble-free processing of the cavity sheet or film in a conventional thermoforming plant and protects the pharmaceutical formulation against contamination in the thermoforming plant after its introduction into the cavity. The filled cavity sheet or film can subsequently be heat-sealed to the cover sheet or film without problems, the latter being preferably perforated, particularly preferably microperforated. FIG. 3 shows a blister pack (4) provided with perforations (8). Where the pharmaceutical formulation is removed by squeezing the cover sheet or film, the perforations are preferably capable of tearing the cover sheet or film along the perforations in the case of pressure on the cavity sheet or film and It is introduced in such a way that the formulation can be removed in a simple manner. Therefore, the invention further relates to a pack according to the invention, characterized in that a single hole, a plurality of holes, perforations or micro-perforations are introduced into the cover sheet or film in any case.

Pharmaceutical formulations that can be included in the pack are all solid pharmaceutical formulations that are in a solid physical state at room temperature, and are intended for, for example, oral, anal or vaginal administration. This means that all solid pharmaceutical formulations intended for direct administration after removal from the container, such as tablets, dragees, hard capsules, granules, pellets, powders, suppositories, and dosage forms that can be administered prior to administration Including those that must be converted to, for example, dried juice, in the form of a powder that must be converted to a solution prior to administration. The pharmaceutical preparation is preferably a tablet, dragee, hard capsule, granular material, suppository, pellet or powder. Hard capsules have a shell to which no plasticizer is added, can be divided into upper and lower parts and consist of, for example, gelatin or starch.
The present invention also provides that the solid pharmaceutical preparation is sealed in a blister pack, and then the sealed blister pack is disposed in one or more inner walls with at least one channel forming portion together with at least one absorbent. It is related with the manufacturing method of a pack characterized by putting in the [drop-off] container which consists of a container which can be sealed tightly incorporated in at least a part of the container.
One or more pharmaceutical formulations above and below are used to mean various technical formulation terms known to administer drugs to humans or animals. Thus, the expression of a pharmaceutical formulation is independent of a particular legal state and is in no way limited to drugs, and various substances may be present as ingredients, for example drugs, dietary supplements and / or functional ingredients. Examples of pharmaceutical formulations for the present invention can be in the form of drugs and dietary supplements.
Surprisingly, the method of the present invention also makes it possible to supply commodities of solid pharmaceutical formulations that have not previously been suitable for sale according to the prior art because they do not have sufficient shelf life. After transferring the formulation to the container, water is removed from the formulation continuously and over a long period of time by the absorbent present on one or more inner walls of the container. Since dehydration is performed under mild conditions over a large area, the result of stabilization of the solid pharmaceutical formulation is obtained during its storage.
Therefore, the present invention is also a method for increasing the shelf life of a solid pharmaceutical formulation, wherein the latter is introduced and sealed in a blister pack, and subsequently the sealed blister pack is attached to one or more inner walls. The method is characterized in that at least one channel forming part is introduced together with at least one absorbent into a container consisting of a tightly sealable container incorporated in at least a part of the region.

The stabilizing action of the pack of the present invention is based on the influence of the container on the solid pharmaceutical formulation contained in the blister pack and, as a result, can be provided in a storage stable manner. Therefore, achievement of the action of the present invention requires that the solid pharmaceutical preparation contained in the blister pack is contained in the container. That is, the pharmaceutical formulation, blister pack and container are both in the form of a pack.
The pack according to the invention has a stabilizing action on all solid pharmaceutical preparations in which one or more active compounds and / or adjuvants are sensitive to moisture. Examples of active compounds that are sensitive to moisture are the active compounds of many drugs, such as hormones or proteins, vitamins, cells, such as probiotic cultures.
The packs of the present invention preferably contain a solid pharmaceutical formulation comprising an active compound that is sensitive to moisture and / or an adjuvant or combination of adjuvants that is sensitive to moisture. The combination of moisture-sensitive adjuvants is, for example, a combination of an organic acid such as citric acid and a carbonate such as sodium bicarbonate or potassium bicarbonate, as used in effervescent tablets.
The solid pharmaceutical formulation contained in the pack of the present invention may further contain conventional adjuvants and additives in some embodiments. The choice of adjuvants and / or additives depends on the provisions of the national food law where the solid pharmaceutical formulation contained in the pack is intended to be used. Auxiliary agents and / or additives are used for tablets, multilayer tablets, dragees, hard capsules, granules, pellet preparations and / or powders, for example, starch (for example, corn starch), talc, microcrystalline cellulose. Lactose, highly dispersed silicon dioxide, polyvinylpyrrolidone and / or cellulose powder. Ingredients that can be present as binders and / or mold release agents are further carbohydrates such as mannitol, sorbitol, xylitol, glucose, sucrose, fructose, maltose, dextrose, maltodextrin and / or kaolin, and / or cellulose. Derivatives such as methylcellulose, hydroxypropylcellulose and / or hydroxypropylmethylcellulose, and / or calcium carbonate, calcium stearate, magnesium stearate and / or glycerol stearate. Furthermore, the pack-containing solid pharmaceutical formulation may contain not only dyes, flavors and / or fragrances but also lubricants, antioxidants and / or stabilizers. The content of these basic substances is on the one hand the target content of the substance to be administered, e.g. drugs, dietary supplements, functional ingredients, on the other hand, a criterion that determines the mechanical and physical properties of the oral formulation, e.g. Depending on hardness, compressibility, size, color and / or shape.
The solid pharmaceutical formulation contained in the pack can also be prepared by various methods known to those skilled in the art. These methods are described, for example, in H. Sucker, P. Fuchs, P. Speiser, “Pharmazeutische Technologie” [Pharmaceutical Technology], Stuttgart 1978 or KH Bauer, KH Froemming, C. Fuehrer, “Pharmazeutische Technologie” [Pharmaceutical Technology], Known from Stuttgart 1986. The descriptions of these references are intended to be included herein and are therefore part of the disclosure.
The examples illustrate the invention but are not limited thereto.

Three-layer tablet similar to EP 931 543 A1 containing probiotic bacteria:
Manufacturing:
3% by weight of bacterial preparation (containing Lactobacillus gasseri, Bifidobacterium bifidum, Bifidobacterium longum), 10.5% by weight of inulin, 8.6 Mass% calcium phosphate, 5.7 mass% cellulose, 2.3 mass% of admixture (disintegrant, mold release agent) mixture (first layer), mineral, trace element, dye, disintegrant, mold release agent, cellulose (first 2 layers) and vitamins, trace elements, disintegrants, mold release agents and cellulose (3rd layer) (percent data in each case based on total tablet weight), 3 layer tablet press from E. Hata (rotary type ) To obtain an elliptical three-layer tablet having a size of 18 mm × 8 mm. Thereafter, the resulting tablets to a film coating over (hydroxypropyl methylcellulose, an aqueous solution containing hydroxypropyl cellulose and a release agent), the coating is 5 mass corresponding to the tablet surface of 11 mg / cm ² based on the weight of the core %become. Three layered tablets each having a mass of 1050 mg are obtained.
Storage and testing:
The stability of film tablets is examined in stability studies. For this purpose, the film tablet is introduced into a PVC / aluminum blister pack (packaging means A) or a PVC / aluminum blister pack, the latter being introduced into a packaging means in which the channel forming part is incorporated with the absorbent on the inner wall. (Packaging means B), store at 40 ° C / 75% RH. After a predetermined time, the tablets are removed from storage and the number of microorganisms present in each case is determined by counting with the Koch pour plate method. The results are shown in Table 1 (average of 3 batches).

表1

table 1

Manufacturing:
A mixture of 10% by weight of nicorandil and adjuvants (filler, disintegrant and mold release agent) is pressed in a tablet machine to obtain round tablets. Tablets having a mass of 100 mg each are obtained.

Claims (13)

  A resealable container having at least one channel forming portion incorporated in at least one portion of the region with at least one absorbent on one or more inner walls, and at least one containing one or more solid pharmaceutical formulations A pack comprising a blister pack, wherein the one or more blister packs are contained in a container.   2. The pack according to claim 1, wherein the container has a rectangular parallelepiped basic shape.   3. The pack according to claim 1, wherein the container has, as an absorbent, a desiccant that binds moisture by physical adsorption.   4. The pack according to claim 3, wherein the desiccant is a molecular sieve or silica gel.   The cavity and / or cover sheet or film of one or more blister packs contained therein is polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), high density polyethylene (HDPE), polypropylene (PP), polyethylene Terephthalate (PET), polycarbonate, cycloolefin copolymer (COC), polychlorotrifluoroethylene (PCTFE), or composite sheets or films made from these materials, such as PVC / PVDC, PVC / HDPE, PVC / PCTFE, The pack according to claim 1, wherein the pack is made of PP / COC or PVC / COC / PVDC.   6. The pack according to claim 5, wherein the cavity and / or the cover sheet or film is made of PVC, PP or PET.   The pack according to claim 1, characterized in that one or more blister packs contained in the pack have at least one hole in each cavity with a solid pharmaceutical formulation.   The pack according to claim 7, characterized in that there are a plurality of holes as perforations in each cavity.   9. A pack according to claim 8, characterized in that the perforations are micro perforations.   10. A pack according to any one of claims 7 to 9, characterized in that a single hole, a plurality of holes, perforations or micro-perforations are introduced into the cover sheet or film in any case.   One or more solid pharmaceutical preparations contained in one or more blister packs contained therein are tablets, dragees, capsules, granules, suppositories, pellets and / or powders, The pack according to claim 1.   12. The method for producing a pack according to any one of claims 1 to 11, wherein the solid pharmaceutical preparation is introduced and sealed in the blister pack, and then the sealed blister pack is attached to one or more inner walls. Said method, characterized in that at least one channel forming part is introduced together with at least one absorbent into a [dropping] container consisting of a tightly sealable container incorporated in at least part of the region.   A method for increasing the shelf life of a solid pharmaceutical formulation, wherein the latter is introduced into a blister pack and sealed, and then the sealed blister pack is provided with at least one channel forming portion on one or more inner walls. Said method, characterized in that it is introduced together with one absorbent into a container consisting of a tightly sealable container incorporated in at least part of the region.

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