WO2008086852A1

WO2008086852A1 - Packaging containing soft capsules

Info

Publication number: WO2008086852A1
Application number: PCT/EP2007/010743
Authority: WO
Inventors: Stefan Henke; Holger Peitz
Original assignee: Merck Patent Gmbh
Priority date: 2007-01-20
Filing date: 2007-12-10
Publication date: 2008-07-24
Also published as: CN101595046B; KR20090103950A; US20100065444A1; MX2009007511A; JP2010516308A; AU2007344507A1; EP2109570A1; RU2009131447A; AU2007344507B2; CA2675892A1; CL2008000141A1; ZA200905771B; CN101595046A; BRPI0720951A2; RU2470846C2

Abstract

The invention relates to a packaging containing a packing means and soft capsules, a method for stabilising soft capsules and a method for producing the packaging.

Description

PACK CONTAINING SOFT CAPSULES

The invention relates to a package comprising a packaging material and soft capsules, a method for stabilizing soft capsules and a method for producing the package.

Soft capsules are capsules due to in the capsule shell additives contained in plasticizers such. As glycerol, sorbitol, maltitol and polyethylene glycols have a certain elasticity and suppleness and for the administration of various substances such. As drugs, nutritional supplements and / or functional ingredients are used. Soft capsules can be prepared, for example, on gelatin or starch basis. Gelatin-based soft capsules have long been known as soft gelatin capsules and are commercially available from various suppliers. Soft capsules based on starch are a relatively new development, an example of which are soft capsules that are sold by Swiss Caps, Switzerland, under the trade name VegaGels ^®.

As far as the soft capsules liquid or semi-solid substances are to be administered, these can be encapsulated directly, solids are previously in liquid or semi-solid bases, such as. As greases, oils, wax mixtures or polyethylene glycols, possibly dissolved or suspended in combination with emulsifiers. Depending on the application path, such. As oral, rectal or vaginal, soft capsules may have different shapes, they may, for. B. round, oval, oblong or torpedo-shaped. Soft capsules can be prepared by the methods known in the art, such as. Example by the Scherer method, the Accogel method or the dripping or blowing process.

The softening effect of the amount of plasticizer contained in the casings of soft capsules is based essentially on its hygroscopicity and the associated incorporation of water the capsule shell. At room temperature (22 ° C./45 to 65% RH (RH = relative humidity)), soft capsules have a water content of about 7 to 8% by weight. % on. If the water content is significantly lower, for example as a result of excessively dry storage or drying, this leads to embrittlement of the capsule shell, with the consequence of increased brittleness of the capsule wall and the formation of cracks. If the water content is significantly exceeded, for example due to storage that is too moist, the capsule shell swells and the soft capsules stick together. Both too dry and too humid storage also leads to unpredictable effects on the substances to be administered and any excipients that may still be present, so that the intended use of the soft capsules supply of the substances contained herein can no longer be ensured. Varying environmental factors lead to completely incalculable influences on the stability of soft capsules, so that their shelf life, ie the period during which the soft capsules are within their respective specifications to be met in order to be properly used, is no longer adequate Safety can be predicted. This is unacceptable, especially for security reasons.

It was an object of the present invention to provide a simple and cost-effective way to avoid both with the embrittlement of the capsule shell as well as by swelling and bonding resulting quality losses and with which the shelf life of soft capsules at high dryness, high humidity, if necessary . also together with high temperatures, as z. B. prevail in the climate zones III and IV, and is significantly increased even in strongly fluctuating humidity.

The object could surprisingly be achieved by the soft capsules was introduced into a packaging, in the Innenwandung / s at least partially an absorbent and at least one channel former is embedded. The invention thus relates to a package comprising a resealable container, in / at the inner wall / s at least part of at least a part Channel former is embedded together with at least one absorbent, and at least one soft capsule, wherein the soft capsule / s contained in the container is / are.

Surprisingly, the introduction of the soft capsules leads to an increase in storage stability, although the container with an absorbent is an agent which has a drying effect. For drying of soft capsules leads via dehydration just embrittlement and fragility of the capsule shell to cracking, so exactly to the state which is avoided by the invention.

According to an advantageous embodiment, the pack according to the invention contains soft gelatine capsules as soft capsules. The subject of the invention is therefore a pack which is characterized in that the soft capsule (s) contained herein is / are a soft gelatin capsule (s).

According to a further advantageous embodiment, the pack according to the invention contains starch-based soft capsules. The invention therefore relates to a pack which is characterized in that the soft capsule (s) contained herein is / are starch-based soft capsule (s).

The container is resealable and can all forms of space, such. B. that of a cylinder or cuboid, provided that it is large enough to accommodate the soft capsules in itself.

Reclosable means that the container can be repeatedly, ie at least once, preferably several times, more preferably at least as often opened and closed again, as it corresponds to the number of soft capsules contained in the container. The container is closed so tightly after each opening and closing process, that penetration of moisture and gases into the container interior is effectively prevented. The container is opened and closed by a tight-fitting closure adapted to the container. It can be used all types of closures, as long as they ensure even after repeated opening and closing of the container that gases and / or moisture in the closed state can not or only in extremely small amounts penetrate into the container interior.

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

According to a preferred embodiment, the container has a cuboidal shape, rounded corners and is well stackable. Such an embodiment is shown by way of example in FIG. The container comprises walls (2), the inwardly directed sides of which at least partially contain at least part of at least one channel former together with at least one absorbent, has rounded corners (7) and has a lid (1) as closure.

The absorbents and channel formers contained in the container can either be contained directly in the inner wall (s) of the polymer forming the container or applied as a layer to the inner wall (s) of the container made of polymers. Likewise, absorbents and channel formers can be embedded in an inlay, which is introduced as an insert into the container, so that at least a part of the inner walls of the container are thereby lined.

Under Innenwandung / s is the inwardly facing surface of the wall / walls of the container understood, ie the area / n of the Container in contact with the soft capsule (s) contained herein.

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

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

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

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

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

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

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

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

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

The pack according to the invention is produced by filling the soft capsule into a resealable container, in which at least part of its inner wall is embedded with at least one channel former together with at least one absorbent, and the container is then closed. The subject matter of the present invention is therefore also a process for the production of a package, which is characterized in that the soft capsule / s is spent in a resealable container, in / on its inner wall at least partially channeled together with at least one absorbent is embedded, and the container is then closed.

The pack according to the invention leads to an increase in the storage stability of the soft capsules contained herein. The invention therefore also provides a process for increasing the storage stability of soft capsules, the characterized in that they are placed in a resealable container, in / on the inner wall / s at least part of the channel at least a channel former is embedded together with at least one absorbent, and the container is then closed.

The stabilizing effect of the pack according to the invention is based on the influence of the container on that in soft capsule / s, which can be made available thereby storage-stable. Achieving the effect according to the invention thus requires that the soft capsule / s is / are contained in the container, that is, the soft capsule / s and container are present together as a package.

In addition to the stabilizing effect on the soft capsule shell leads in the package of the invention also to a stabilization of the active ingredients and / or auxiliaries contained in these, ie the entire formulation. This is especially true when the active ingredients and / or adjuvants contained are sensitive to moisture. Examples of moisture-sensitive agents which are thus preferably contained in the soft capsules in the package are many pharmaceutical agents such as hormones or proteins, vitamins, cells, e.g. probiotic cultures.

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

example 1

Investigation of the stability of soft capsules in the package according to the invention in comparison to soft capsules in conventional packaging

Multivitamin soft capsules (active ingredient composition and capsule shell as described below) are separated into a thermoformed PVC 250 μm + 40 g / m ² PVDC and sealed with aluminum foil (20 μm) or in a resealable container, in / on the inner wall / s at least part of the channel at least one channel former is embedded together with at least one absorbent, spent (type: M-3006-16 Activ-Vial), in the inner walls of a molecular sieve with a capacity of 1, 92 g is embedded.

The blisters and containers containing the multivitamin soft capsules are stored at 40 ⁰ C and 75% relative humidity (RH), outsourced after predetermined times, visually assessed in terms of their appearance and analyzed analytically with regard to the amounts of active ingredient contained. The results are summarized in Tables 1 and 2.

Table 1

* Composition of the soft capsule shell: gelatin 209.76 mg, glycerol 85% 65.83 mg, sorbitol solution 70% 44.21 mg, black iron oxide 1.22 mg, red iron oxide 3.89 mg.

Table 2

^* Composition of the soft capsule shell: gelatin 209.76 mg, glycerol 85% 65.83 mg, sorbitol solution 70% 44.21 mg, black iron oxide 1.22 mg, red iron oxide 3.89 mg.

Example 2

Investigation of the stability of soft capsules in the package according to the invention

Multivitamin soft capsules (active ingredient composition and capsule shell as described below) are in a resealable container, in / on the inner wall / s at least part of at least part of channel at least one channel former embedded with at least one absorbent, spent (Type: M-3006-16 Activ-Vial) , in whose inner walls a molecular sieve with a capacity of 1, 92 g is embedded.

The multivitamin soft capsules are stored at 30 ⁰ C and 65% relative humidity (RH), outsourced after predetermined times, visually assessed in terms of their appearance and in terms of analyzed active ingredient levels. The results are summarized in Table 3.

Table 3

^* Composition of the soft capsule shell: gelatin, glycerol 98-100%,

Sorbitol solution 70%, water

Claims

claims

A package comprising a resealable container, in / on the inner wall of which at least part of the channel at least one channel former is embedded together with at least one absorbent, and at least one soft capsule, the soft capsule / s being contained in the container.

2. A package according to claim 1, characterized in that the soft capsule (s) is a soft gelatin capsule (s).

A package according to claim 1, characterized in that the soft capsule is a starch-based soft capsule (s)

4. Pack according to one or more of claims 1 to 3, characterized in that the container has a cuboid-shaped basic shape.

5. A package according to one or more of claims 1 to 4, characterized in that the container contains as absorbent a desiccant, which binds moisture by physical adsorption.

6. A package according to claim 5, characterized in that the desiccant is a molecular sieve or silica gel.

7. A method for producing a package according to one or more of claims 1 to 6, characterized in that the soft capsules / n is spent in a resealable container / in the inner wall / s at least part of at least part of channel at least one channel former together with at least one Absorbent is embedded, and the container is then closed.

8. A method for increasing the storage stability of soft capsules, characterized in that they are spent in a resealable container, in / on the inner wall / s at least part of at least one Channel former is embedded together with at least one absorbent, and the container is then closed.