JP2010516308A - Pack containing soft capsules - Google Patents

Abstract

  The present invention relates to a packaging material and a pack containing soft capsules, a method for stabilizing soft capsules, and a method for producing said packs.

Description

  The present invention relates to a packaging material and a pack containing soft capsules, a method for stabilizing soft capsules, and a method for producing said packs.

  Soft capsules have a certain elasticity and flexibility due to the addition of softeners such as glycerol, sorbitol, maltitol and polyethylene glycol present in the capsule shell, e.g. for drugs, supplements and / or functional ingredients. It is a capsule used for administration of various substances. Soft capsules can be produced, for example, based on gelatin or starch. Gelatin-based soft capsules have long been known as soft gelatin capsules and are commercially available from various suppliers. Starch-based soft capsules are a relatively new development, an example being the soft capsule marketed by Swiss Caps (Switzerland) under the trade name VegaGels ™.

  If liquid or semi-solid materials are to be administered by soft capsules, they are directly encapsulated and the solid is initially a liquid or semi-solid base (such as a fat, oil, wax mixture or polyethylene glycol). Or may be mixed with an emulsifier. Depending on the method of administration (such as oral, rectal or vaginal), the soft capsule can take various forms, for example round, oval, rectangular or torpedo-shaped. It may be. Soft capsules can be produced by methods known in the art, such as the Scherer process, the Accogel process or the droplet or blowing process.

  The softening action of the softener component present in the soft capsule shell is essentially based on its hygroscopicity and is associated with the incorporation of water into the capsule shell. At room temperature (22 ° C./45-65% RH (relative humidity)), the moisture content of the soft capsule is about 7-8% by weight. If the moisture content is significantly less than this, for example, excessive dry storage or drying results in embrittlement of the capsule shell, accompanied by increased capsule wall fragility and crack formation. If the moisture content is significantly higher than this, capsule shell swelling and soft capsule sticking occur, for example, due to excessive wet storage. Excessive dry storage and excessive wet storage both have an unpredictable effect on the administered substance and other auxiliaries present, which means that the supply of the existing substance, which is intended by taking soft capsules, is no longer present. It means that it cannot be guaranteed. Changing the environmental impact has a totally unpredictable impact on the stability of the soft capsules, which must be met so that the shelf life, i.e. the soft capsules are taken as intended, each applied It means that a period that is within the specification can no longer be predicted with the required certainty.

  The object of the present invention is to avoid the qualitative losses caused by the embrittlement and swelling and sticking of the capsule shell, and as prevail, for example in climatic zones III and IV, and in cases where atmospheric humidity changes significantly. It is to find a simple and inexpensive way to significantly extend the shelf life of soft capsules under the high dryness and high atmospheric humidity that can occur with high temperatures.

  Surprisingly, the object has been achieved by introducing soft capsules into a packaging material in which a hygroscopic agent and at least one channel-forming agent are embedded in at least part of the region of its inner wall. Accordingly, the present invention comprises a re-closeable container having at least one channel forming agent embedded with at least one hygroscopic agent in at least a portion of the region in / on the inner wall, and at least one soft capsule, It relates to a pack in which soft capsules are present in said container.

  Surprisingly, in containers containing hygroscopic agents, there are drugs that provide a drying effect, but storage of soft capsules results in an extended shelf life. This is because the drying of the soft capsules leads to a state where the removal of water precisely causes the capsule shell to become brittle and even brittle or even cracked, i.e. the state avoided by the present invention.

An example of an embodiment is shown.

  According to an advantageous embodiment, the pack according to the invention comprises soft gelatin capsules as soft capsules. The invention therefore relates to a pack characterized in that the existing soft capsules are soft gelatin capsules.

  According to a further advantageous embodiment, the pack according to the invention is included as a starch-based soft capsule. The invention therefore relates to a pack characterized in that the existing soft capsules are starch-based soft capsules.

  The container can be closed again and can have any spatial shape, for example a columnar or cubic shape, provided that it is large enough to accommodate a soft capsule inside.

  Being able to close again means that the container can be opened and closed again repeatedly, ie at least once, preferably many times, particularly preferably at least as many times as the number of soft capsules present in the container. To do. The container is tightly sealed after each opening and sealing operation to such an extent that moisture and gas can be effectively prevented from entering the container.

  The container is opened and sealed by a tightly sealed closure adapted to the container. All types of gas and / or moisture, even after repeated opening and closing of the container, as long as it is ensured that it cannot penetrate into the interior of the container in a sealed state or only penetrates in extremely small amounts Closures can be used.

  According to an embodiment of the invention, the lid is used as a closure. Examples of lids include a screw cap, a cap that reverses at the top of the container, or a cap that is introduced into the interior of the container. For example, in the case of special shapes with corners such as cubes, the corners of the opening and the matching lid are also slightly rounded to increase the tightness of the container against gas and moisture.

  According to a preferred embodiment, the containers have a special cubic shape, rounded corners and are easily stacked. This type of embodiment is described by way of example in FIG. The container has a wall (2) comprising at least one channel-forming agent together with at least one hygroscopic agent so that the inwardly facing side surface covers at least part of the region, rounded corners (7) And the lid (1) as a closure.

  The hygroscopic agent and channel forming agent present in the container may be present together directly on the inner wall of the polymer forming the container, or may be applied together as a layer on the inner wall of the polymer container. Similarly, the hygroscopic agent and channel forming agent may be embedded in an inlay that is introduced into the container as an insert and at least a portion of the inner wall of the container is covered thereby.

  The inner wall means the surface facing the inside of the container wall, i.e. the surface of the container in contact with the soft capsules present therein.

  A suitable material for the container is a polymer. Polymers that can be used in mixtures with hygroscopic agents and channel formers are in particular thermoplastic resins such as, for example, polyolefins, such as polyethylene and / or polypropylene, polyisoprene, polybutadiene, polybutene, polysiloxane, polyamide, ethylene-acetic acid. Vinyl copolymer, ethylene-methacrylate copolymer, polystyrene, polyester, polyanhydride, polyacrylate nitrile, polysulfonate, polyesteramide, polyacrylate ester, propylene-maleic anhydride, polyethylene-maleic anhydride, polyethylene-urethane, Examples include polyethylene-ethyl vinyl alcohol, polyethylene-nylon and / or polyurethane. The wall having the hygroscopic agent and the channel-forming agent on the inner surface has a polymer content of 10-90% by weight, based on the total weight of the polymer, channel-forming agent and hygroscopic mixture.

  The hygroscopic agent that can be present is in principle any type of desiccant, ie a water-binding binder. Three groups of desiccants are described.

  The first group includes chemicals that form hydrates with water. An example of this type of chemical is an anhydrous salt, which tends to absorb water or moisture and forms stable hydrates in the process. It binds moisture and its release is prevented by chemical reaction.

  The second group of desiccants includes substances that are reactive. The substance reacts with water or moisture by forming a new substance. Newly formed materials are usually stable at low temperatures and are reversible only by consuming high energy. This type of desiccant is primarily used to dry solvents and is used as a hygroscopic material in polymers that themselves must remain dehydrated.

  A third group of desiccants binds moisture by physical adsorption. The desiccant includes particles having fine pores that draw moisture. The pore size and density of the pores in the desiccant determines the absorption characteristics. Examples of this type of desiccant are molecular sieves, silica gels, certain synthetic polymers such as those used in baby diapers, and starches. The third group of desiccant is preferably present in the container because it is substantially inert and insoluble in water. Particular preference is given to molecular sieves having a pore size of 3 to 15 and / or silica gels having a size of 24 to.

  Suitable channel formers are hydrophilic substances such as, for example, 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. Sugars 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 means for example dextrin and / or hydrolyzed starch.

  In the inner wall having the humectant and the channel former, the channel builder can have a ratio of 10 to 40% by weight, based on the total weight of the polymer, channel former and humectant mixture.

  The hygroscopic agent and the channel forming agent are embedded in a part of the surface of the inner wall of the container or over the entire area. “Part of the region” means that at least a part of the entire region of the container forming the inner wall contains a hygroscopic agent and a channel forming agent.

  Over the whole area means that the whole area of the container forming the inner wall contains a hygroscopic agent and a channel forming agent. According to an advantageous embodiment, the hygroscopic agent and the channel forming agent are present in at least 10%, preferably at least 50%, particularly preferably at least 90% of the inner wall, based on the total surface area inside the container.

  Containers comprising a hygroscopic agent and a channel forming agent and formed from a polymer suitable as a packaging container of the present invention are known in the prior art, for example WO 97/32663 A1, EP 1000873 A2 and WO 03/086900 A1 EP 1421991 A1. Containers that can be used in the packs of the present invention are commercially available, for example from Capitol Specialty Plastics Inc. (2039 McMillan Street Auburn, Alabama, USA) under the trade name Activ-Vial or Sud Chemie (Ostenrieder Str. 15, 85368 Moosburg , Germany) under the trade name 2 AP Multipolymer.

  The pack of the present invention places a soft capsule in a re-closeable container in which at least one channel former is embedded with at least one hygroscopic agent in at least a portion of the area in / on the inner wall, and then seals the container Formed by. Accordingly, the present invention also relates to a method of forming a pack, which can be closed again with at least one channel forming agent embedded with at least one hygroscopic agent in at least a portion of the region in / on the inner wall. It is characterized in that a soft capsule is introduced into the resulting container and then the container is sealed.

  The pack of the present invention extends the shelf life of the soft capsules present therein. Accordingly, the present invention also relates to a method for extending the shelf life of a soft capsule, which method is reclosed with at least one channel former embedded with at least one hygroscopic agent in at least a portion of the region in / on the inner wall. It is characterized in that a soft capsule is introduced into a container which can then be sealed.

  The stabilizing action of the pack of the present invention is based on the effect of the container on the soft capsule, which can be used with a long shelf life. Thus, in order to achieve the operation of the present invention, it is necessary that the soft capsule exists in the container, that is, both the soft capsule and the container are in the form of a pack.

  Besides the stabilizing action on the shell of the soft capsule, it provides the stabilization of the active compound and / or auxiliaries present therein, i.e. the entire formulation, in the pack of the invention. This is especially true when the active compounds and / or auxiliaries present are sensitive to moisture. Thus, examples of moisture sensitive active compounds that are suitably present in soft capsules in packs are many pharmaceutically active compounds such as hormones or proteins, vitamins, cells, eg probiotic cultures.

  The following examples illustrate the invention, but the invention is not limited thereto.

Example 1
Investigation of the stability of soft capsules in the pack of the present invention compared to soft capsules in conventional packaging materials Multivitamin soft capsules (active compound composition and capsule shells below) from PVC 250μm + 40g / m ² PVDC At least a channel forming agent is formed in at least a part of the area in / on the thermoformed cavity film and the inner wall heat-sealed and heat sealed with aluminum foil (20 μm) (type: M-3006-16 Activ-Vial) (with an inner wall embedded with a molecular sieve having a capacity of 1.92 g) separately introduced into a re-closable container.

  Store blisters and containers containing multivitamin soft capsules at 40 ° C and 75% relative humidity (RH), remove from storage after a specified time, visually evaluate their appearance, and amount of active compound present Was analyzed. The results are summarized in Tables 1 and 2.

*ソフトカプセルの殻の組成：ゼラチン209.76mg、グリセロール85％65.83mg、ソルビトール溶液70％44.21mg、黒色酸化鉄1.22mg、赤色酸化鉄3.89mg。

* Soft capsule shell composition: gelatin 209.76mg, glycerol 85% 65.83mg, sorbitol solution 70% 44.21mg, black iron oxide 1.22mg, red iron oxide 3.89mg.

*ソフトカプセルの殻の組成：ゼラチン209.76mg、グリセロール85％65.83mg、ソルビトール溶液70％44.21mg、黒色酸化鉄1.22mg、赤色酸化鉄3.89mg。

* Soft capsule shell composition: gelatin 209.76mg, glycerol 85% 65.83mg, sorbitol solution 70% 44.21mg, black iron oxide 1.22mg, red iron oxide 3.89mg.

(Example 2)
Investigation of the stability of soft capsules in the packs of the present invention Multi-vitamin soft capsules (active compound composition and capsule shell as described below) with at least one channel-forming agent in at least part of the area in / on the inner wall It was introduced into a re-closable container embedded with one hygroscopic agent (type: M-3006-16 Activ-Vial) (with an inner wall embedded with a molecular sieve having a capacity of 1.92 g).

  The multivitamin soft capsules were stored at 30 ° C. and 65% relative humidity (RH), removed from the storage location after a predetermined time, visually evaluated for their appearance, and analyzed for the amount of active compound present. The results are summarized in Table 3.

*ソフトカプセルの殻の組成：ゼラチン、グリセロール98-100％、ソルビトール溶液70％、水。

* Soft capsule shell composition: gelatin, glycerol 98-100%, sorbitol solution 70%, water.

Claims (8)

  At least a portion of the region in / on the inner wall comprising at least one channel-forming agent embedded in at least one hygroscopic agent and a closable container, and at least one soft capsule, wherein the soft capsule is in the container An existing pack.   The pack of claim 1, wherein the soft capsule is a soft gelatin capsule.   The pack of claim 1, wherein the soft capsule is a starch-based soft capsule.   The pack according to claim 1, wherein the container has a cubic basic shape.   The pack according to any one of claims 1 to 4, wherein the container includes a desiccant that binds moisture by physical adsorption as a hygroscopic agent.   The pack according to claim 5, wherein the desiccant is molecular sieve or silica gel.   7. The method for producing a pack according to any one of claims 1 to 6, wherein at least one channel forming agent is embedded together with at least one hygroscopic agent in at least a part of the region in / on the inner wall. The production method characterized in that a soft capsule is introduced into a container capable of sealing and subsequently the container is sealed.   A method for increasing the shelf life of a soft capsule, wherein the soft capsule is introduced into a re-closable container in which at least one channel-forming agent is embedded with at least one hygroscopic agent in at least part of the area in / on the inner wall And subsequently sealing the container.

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