BRPI0720951A2 - PACKAGING CONTAINING SOFT CAPSULES. - Google Patents

Description

Patent Descriptive Report for "PACKAGING CONTAINING SOFT CAPSULES".

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

Soft capsules are capsules which, due to the addition of softener, such as, for example, glycerol, sorbitol, maltitol and polyethylene glycols, present in the shell of the capsule, have a certain elasticity and softness and are employed for the administration of various substances, such as, for example, medicines, food supplements and / or functional ingredients. Soft capsules may be produced, for example, based on gelatin or starch. Soft gelatin 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, one example being soft capsules sold by Swiss Caps, Switzerland under the trademark Vega-Gels®.

If liquid or semi-solid substances are to be administered via soft capsules, they may be directly encapsulated, solids are first dissolved or suspended in liquid or semi-solid bases, such as, for example, fats, oils, mixtures of wax or polyethylene glycols, possibly in combination with emulsifiers. Depending on the method of administration, such as, for example, orally, rectally or vaginally, soft capsules may have various shapes, they may be, for example, round, oval, oblong or torpedo-shaped. Soft capsules may be produced by processes known in the prior art, such as, for example, by the Scherer process, the Accogel process or the droplet or blow process.

The softening action of the present fabric softener component

in soft shell shells it is essentially based on their hygroscopicity and the associated inclusion of water in the shell of the 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. If the water content is significantly below this, for example due to excessively dry storage or drying, this results in susceptibility to cracking of the capsule shell, with the consequence of increased capsule wall brittleness and cracking. If the water content is significantly above this, for example due to excessively wet storage, capsule shell swelling and adhesion together of the soft capsules occur. Both excessively dry and excessively wet storage also result in unpredictable effects on the substances being administered and any additional aids present, meaning that the supply with the substances present in them that is intended with ingestion of the soft capsules can no longer occur. be assured. Variable environmental influences result in totally incalculable influences on the stability of soft capsules, meaning that their shelf life, that is, the period during which soft capsules fall within their respective specifications applicable to them. met so that they can be taken as intended can no longer be foreseen with the necessary certainty. This is unacceptable, in particular also for safety reasons.

The aim of the present invention was to find a simple and economical way to prevent quality losses that arise both with the capsule shell being brittle and also due to swelling and adherence together and significantly increasing the shelf life of soft capsules. very dry environment, high atmospheric humidity, possibly also together with high temperatures, which prevail, for example, in NI and IV climatic zones, and also in the case of strongly variable atmospheric humidity.

The goal was surprisingly achieved by introducing the soft capsules into a packaging material on the side wall (s) from which an absorbent and at least one channel former is soaked, at least in part. of the area. The invention then relates to a package comprising a container that can be opened at the side wall (s) from which at least one channel former is embedded, at least in part of the area, along with at least one absorbent, and at least one soft capsule, where the soft capsule (s) is (are) present in the container.

Surprisingly, storage of the soft capsules results in an increase in shelf life, although the container with an absorbent agent is present which results in a drying action. This is because the drying of soft capsules results, through the removal of water, precisely in brittle quality and brittleness of the shell of the capsule or even breaking, that is precisely the state that is avoided by the invention.

According to an advantageous embodiment, the package according to the invention contains soft gelatin capsules as soft capsules. The invention thus relates to a package which is characterized in that the capsule (s) present therein are soft gelatin capsule (s).

According to a further advantageous embodiment, the package according to the invention contains a starch-based soft capsule. The invention thus relates to a package which is characterized in that the soft capsule (s) present are starch soft capsule (s).

The container may be open and may have any spatial shape, such as, for example, that of a cylinder or cuboid, as long as it is large enough to accommodate the soft capsules within it.

Openable means that the container can be opened and closed repeatedly, i.e. at least once, preferably several times, particularly preferably at least as often as the number of soft capsules present in the container. . The container is also hermetically sealed after each opening and closing operation that ingress of moisture and gases into the container is effectively prevented.

Container opening and closing is accomplished by a firm sealing closure attached to the container. All types of closures can be employed as long as they ensure that gases and / or moisture cannot penetrate inside the container in the closed state, or can only do so in extremely small quantities even after repeated opening and closing of the container. container.

According to one embodiment of the invention, lids are used as closures. Examples of lids are screw caps, lids 10 which are inverted over the top edge of the containers or inserted into the container. In the case of space shapes having corners such as cuboid, the opening corners and the attached lid may also be slightly rounded to increase the firmness of the container against gases and moisture.

According to a preferred embodiment, the container has a

cuboidal shape, spatial shape, rounded edges and is stackable. Such an embodiment is shown by way of example in Figure 1. The container comprises walls (2) whose inwardly facing sides contain at least part of the area at least one channel former together with at least one absorbent. , has rounded corners (7) and has a lid (1) as closure.

The absorbers and channel formers present in the container may together or be present directly on the inner wall (s) of the polymer forming the container or applied as a layer 25 to the inner wall (s). s) of the polymeric container. Similarly, absorbents and channel formed may be soaked in a filler which is introduced into the container as an insert so that at least part of the inner walls of the container are coated.

Inner wall (s) means the surface facing the inside of the container walls / walls, ie the container surface (s) that are in contact with the capsule (s). ) soft gifts on it.

Suitable materials for the container are polymers. Polymers, which may be employed in a mixture with absorbents and channel formers, are in particular thermoplastics, such as, for example, 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 polyethyl anhydride, maleic anhydride maleic anhydride, polyethylene urethanes, polyethylene ethyl vinyl alcohols, polyethylene nylon and / or polyurethanes. The walls provided with absorbents and channel formers 10 on their inner surface have, based on the total weight of the polymer blend, channel formers and absorbers, a polymer content of 10-90% by weight.

Absorbents that may be present are at first any kind of desiccants, ie moisture binding binders. Three dissecting groups are considered:

The first group contains chemicals that form hydrates with water. Examples of chemicals of this type are water salts, which tend to absorb water or moisture and form a stable hydrate in the process. Moisture is turned on, and its release is prevented by a chemical reaction.

The second group of dissectors contains substances that are reactive. Substances react with water or moisture by forming a new substance. Newly formed substances are usually stable at low temperatures, which is only reversible with high energy expenditure. Desiccants of this type are mainly used for solvent drying and as a water absorbing material in polymers that have to be kept in a low humidity state.

The third group of desiccants binds to moisture through physical adsorption. The desiccant contains particles having thin capillaries to which moisture is attracted. The pore size of the capillaries and the density of the capillaries in the dissector determine the absorption properties. Examples of such desiccants are molecular sieves, silica gels, certain synthetic polymers, such as, for example, those used in baby diapers and starches. Third group desiccants are preferably present in the container since they are substantially inert and insoluble in water. Particular preference is given to molecular sieves having a pore size of 3 to 15 Angstroms and / or silica gels having a pore size of 24 Angstroms.

Suitable channel formers are hydrophilic substances, such as, for example, polyglycols, ethylvinyl alcohols, glycerol, polyvinyl alcohols, polyvinylpyrrolidone, vinylpyrrolidone, N-methylpyrrolidone, polysaccharides, saccharides and / or sugar alcohols. Preferred polyglycols are polyethylene glycol and / or polypropylene glycol. Saccharides which may 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. Polysaccharides mean, for example, dextrins and / or hydrolyzed starch.

In the inner walls provided with absorbers and channel formers, channel formers may have a proportion of 10-40% by weight, based on the total weight of the polymer blend, channel formers and absorbers.

Absorbents and channel formers are soaked in part of the

surface or the entire area of the inner wall (s) of the container. Part of the surface means that at least part of the total container area forming the inner wall (s) comprises absorbers and channel formers.

In total area means that the entire area of the container forming the

Inner walls comprise absorbers and channel formers. According to an advantageous embodiment, absorbent and channel forming agents are present in at least 10%, preferably at least 50%, particularly preferably at least 90% of the inner walls, based on the total inner surface area of container.

Containers made of polymers comprising absorbent and channel forming agents and which are suitable as packaging containers according to the invention are known in the prior art and are described, for example, in WO 97/32663 A1, EP 1000873 A2 and WO 03/086900 A1, EP 1421991 A1. Containers which may be employed in packaging according to the invention are commercially available and are available, for example, from Capitol Specialty Plastics, Inc., 2039 McMiIIan Street Auburn, Alabama, USA under the trademark Activ-Vial or Sud Chemie, Ostenrieder Str. 15, 85368 Moosburg, Germany, under the trademark 2 AP Multipolymer.

The package according to the invention is produced by distributing the soft capsule (s) in an openable container in the wall (s) of which at least one channel former is formed. it is soaked, at least in part of the area, together with at least one absorbent and subsequently sealing the container. The present invention then also relates to a process for producing a package which is characterized in that the soft capsule (s) are introduced into a container which may be opened in the side wall (s) from which at least one channel former is embedded, at least part of the area, together with at least one absorbent, and the container is subsequently sealed.

The packaging according to the invention results in an increase in shelf life of the soft capsules present therein. The invention also relates to a process for extending the shelf life of soft capsules which is characterized by the fact that they are introduced into a container that can be opened on the wall (s). of which at least one channel former is soaked, at least in part of the area, together with at least one absorbent, and the container is subsequently sealed.

The stabilizing action of the package according to the invention is based on the influence of the container on the soft capsule (s), which can therefore be made available with a long shelf life. Obtaining action according to the invention then requires that the soft capsule (s) are present in the container, ie the soft capsule (s) and container together in the form of a package.

In addition to the stabilizing action on the soft shell shell, the packaging according to the invention also results in stabilization of the active and / or auxiliary compounds present therein, that is, the whole formulation. This applies in particular if the active and / or auxiliary compounds present are moisture sensitive. Examples of moisture sensitive active compounds which are then preferably present in soft capsules in the package are many active pharmaceutical compounds, such as hormones or proteins, vitamins, cells, such as, for example, probiotic cultures.

The examples explain the invention without being restricted to them.

Example 1

Investigation of the stability of soft capsules in packaging according to the invention compared to soft capsules in conventional packaging materials.

Soft multivitamin capsules (composition of active compound and capsule shell as described below) are individually inserted into a thermoformed cavity film made of 250 pm PVC + 40 g / m2 PVDC and heat sealed with aluminum foil. (20 pm) and at 20 a container that can be opened in the inner wall (s) from which at least one channel former is soaked, at least in part of the area, together with at least one absorbent ( type: M-3006-16 Activ-Vial) on the inner walls of which a molecular sieve having a capacity of 1.92 g is embedded.

The blisters and containers containing the soft capsules of

Vitamins are stored at 40 ° C and 75% relative humidity (RH), removed from storage after predetermined times, visually assessed for appearance, and analytically investigated for amounts of active compound present. Results are compiled in Tables 1 and 2. Table 1

Product Multivitamin Soft Capsule * Batch 9018401 Packaging Material PVC / PVDC-Aluminum Blister Storage Condition Cond 40 ° C / 75% RH Storage Duration Duração Beginning 3 months Parameter mg / capsule% mg / capsule% Ascorbic Acid 209 100 159 76 Dexpanthenol 13.5 100 9.7 72 Thiamine HCL * 19.7 100 17.1 87 Cyanocobalamin 0.199 100 0.171 86 Folic acid 0.62 100 0.57 92 * Soft capsule shell composition: gelatin 209, 76 mg, glycerol 85%,

65.83 mg, 70% sorbitol solution 44.21 mg, black iron oxide 1.22 mg, red iron oxide 3.89 mg.

Table 2

Product Multivitamin Soft Capsule * Batch 9018802 Packaging Material Inner wall container from which a channel former and an absorbent are soaked Storage condition¬ 40 ° C / 75% RH ment Shelf life¬Start 6 months mg / capsule% mg / capsule% Ascorbic acid 213 100 210 99 Dexpanthenol 13.3 100 12.8 96 Thiamine HCL * 19.6 100 19.3 98 Cyanocobalamin 0.21 100 0.173 82 Folic acid 0.60 100 0.520 87 * Soft capsule shell composition: gelatin 209.76 mg, glycerol 85%, 65.83 mg, sorbitol solution 70% 44.21 mg, iron oxide black 1.22 mg, red iron oxide 3.89 mg.

Example 2

Investigation of the stability of soft capsules in packaging according to the invention.

Multivitamin soft capsules (active compound composition and capsule shell as described below) are introduced into an openable container in the inner wall (s) from which at least one channel former is embedded, by least part of the area, together with at least 10 absorbent (type: M-3006-16 Activ-Vial) on the inner walls of which a molecular sieve having a capacity of 1.92 g is embedded.

Multivitamin soft capsules are stored at 30 ° C and 65% relative humidity (RH), removed from storage after predetermined times, visually evaluated for appearance, and analytically investigated for amounts of active compound present. The results are compiled in Table 3.

Table 3

Product Multivitamin Soft Capsule * Batch GD 06 0045 Packaging Material Inner wall container from which a channel former and an absorbent are soaked Storage condition¬ 30 ° C / 65% RH ment Storage duration¬Start 6 months Parameter mg / capsule% mg / capsule% β-carotene 2,3 100 2,0 87 Thiamine nitrate 2,40 100 2,37 99 Riboflavin 2,09 100 2,23 107 Nicotinamide 20,6 100 20,1 98 Pyridoxine HCL * 3.60 100 3.39 94 Product Multivitamin Soft Capsule * Ascorbic Acid 120.5 100 115.0 95 Tocopherol Acetate 20.0 100 19.8 99 Folic Acid 0.581 100 0.603 104 Biotin 0.176 100 0.185 105 Cyanocobalamin 0.0163 100 0.0158 97 Calcium pantothenate 15.6 100 14.9 96 * Soft capsule shell composition: gelatin, glycerol 98-100%, sorbitol 70% solution, water.

Claims (8)

A package comprising a container that can be opened on the inner wall (s) from which at least one channel former is soaked, at least in part of the area, together with at least one absorbent. , and at least one soft capsule, wherein the soft capsule (s) is (are) present in the container. Packaging according to claim 1, characterized in that the soft capsule (s) are (one) soft gelatin capsule (s). Packaging according to Claim 1, characterized in that the soft capsule (s) are (a) starch-based soft capsule (s). Packaging according to one or more of Claims 1 to 3, characterized in that the container has a basic cuboidal shape. Packaging according to one or more of Claims 1 to 4, characterized in that the container contains, as an absorbent, a desiccant which binds to moisture through physical adsorption. Packaging according to Claim 5, characterized in that the desiccant is a molecular sieve or silica gel. A process for producing a package as defined in one or more of claims 1 to 6, characterized in that the soft capsule (s) are introduced into a container which may be opened in the inner wall (s) from which at least one channel former is embedded in at least part of the area together with at least one absorbent and the container is subsequently sealed. Process for extending shelf life of soft capsules, characterized in that they are introduced into a container that can be opened in the inner wall (s) of which at least one channel former it is soaked, at least in part of the area, together with at least one absorbent, and the container is subsequently sealed.