DE3438656A1 - CAPSULE - DOSAGE FORMS - Google Patents

Description

WARNER-LAMBERT COMPANY PD (314O) A.

CAPSULE DOSAGE FORMS

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Capsule Dosage Forms

The present invention relates to dosage forms of hard-shell capsules for the metered administration of solid, creamy and liquid substances, especially pharmaceuticals.

The dosage form of the present invention consists of two or more capsules that are linked together. Included the connecting pieces of the capsules can be made in one operation with the capsule production by pressure molding and from the same Materials such as the capsules can be manufactured- Further, the capsules can have two or more non-separable sections or sectors Contained in each capsule to accommodate various medications. The types of capsules according to the invention can be used as a A large number of single doses or packs can be produced. Previously known capsules for pharmaceutical use have only one container to hold filling material, namely the one created by pushing the cap and body parts together preserved cavity of the capsule.

It is known that tablets offer the patient the option of reducing the dosage, e.g. by breaking it into pieces Select. According to the present invention, capsules can now be made using compression molding techniques, preferably by means of injection molding are manufactured that contain two or more drugs that are not in a tablet or in previously common capsules could be combined, as their active substances, e.g. react with each other to form undesirable products.

Capsule dosage forms according to the present invention can be used in smaller units are divided and swallowed. The articles of the present invention can be compression molded, preferably Injection molding of starch, hydrophilic polymers such as gelatin, or

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Starch derivatives, all with low water contents.

In injection molding, it is important that the molten material behaves like a thermoplastic material during the molding process and then quickly turns into solidifies in the form so that it can be ejected from the form quickly and without changing dimensions. The latter is therefore of of particular importance because most compression molded articles require a high degree of dimensional stability. The articles according to the invention can be produced with the highest accuracy and dimensional stability by pressure molding, in particular injection molding.

According to the invention, in particular a hydrophilic polymer or a mixture of such polymers suitable with a water content of 5-25% (calculated on the hydrophilic water-containing polymer mixture) and in the event that gelatin is used, this has a water content of 10-20% by weight (calculated on the water-containing gelatin mixture), and / or starch or a starch mixture with a water content of 5-25% by weight, preferably 15-21% by weight (calculated on the water-containing starch mixture).

The present invention relates to divisible hard shell Capsule shapes, characterized in that the individual capsule units, each consisting of a cap part and a Body parts that can be pushed into one another are connected to one another in such a way that the individual capsule units are easily can be separated from each other.

The present invention also relates to hard-shell capsule shapes, consisting of a cap part and a body part, characterized in that the body part has several compartments. These individual capsule units can be connected to form larger units by means of one or more lamellae.

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The invention also relates to hard-shell capsule packs, characterized in that the individual capsule units consisting of a cap part and a body part that fit into each other are slidable, are connected to one another in such a way that the individual capsule units are easily separated from one another can. The connected capsule units of the present invention are preferably connected to one another by one or more thin lamellae tied together; these connected units are preferably produced in a single operation by means of the injection molding process.

According to the invention, the individual capsule units or the individual departments of a body part can be filled with different drugs, for example.

The capsule units can be used for precise dosing of solid, liquid and creamy substances, mainly in the pharmaceutical field.

Preferred capsules according to the present invention are made from Starch made by injection molding.

Injection molding of hydrophilic material such as water-based Gelatin, is in European Patent Pub. No. 92908 and is part of the present invention.

Hydrophilic polymers are polymers with molecular masses of approximately 10 to 10 Daltons which contain molecular groups in their main chain and / or in side chains which are capable of forming and / or participating in hydrogen bonds. The processing temperatures for these materials are in the range of preferably 70-190 ^° C., preferably 80-190 ^° C.,

If gelatin is used as the hydrophilic polymer, it is produced e.g. by acidic or alkaline treatment of collagen, acidic treatment of pig skin or alkaline treatment of Cowhides. These types of gelatin have molecular masses preferably in the range from 10,000 to 2 × 10 Dalton or molecular masses in the range from 10,000 to 2 χ 10 and 10 χ 10 to 20 χ 10 daltons. The gelatin used has one Water content of preferably 10-19%, particularly preferably 12-18% by weight, based on the water-containing gelatin mixture.

All hydrophilic polymers, including gelatine, can contain various additives such as plasticizers, lubricants, Crosslinking agents and dyes - as described in European patent application Publ. 92908 described - be added. The hydrophilic polymers can also contain up to 95%, preferably not more than 30% by weight, of extenders, such as proteins e.g., sunflower proteins, soybean proteins, cottonseed proteins; Peanut proteins, blood proteins, egg proteins, Rapeseed proteins and their acrylated derivatives, cross-linked gelatine, vinyl acetates, polysaccharides such as cellulose, methyl cellulose, Hydroxymethyl cellulose, sodium carboxymethyl cellulose, agar-agar, gum arabic, guar, dextran, chitin, polymaltose, Polyfructose, pectin, alginates, alginic acid, monosaccharride like Glucose, fructose, sucrose, oligosaccharides such as lactose, Contain polyvinylpyrrolidone, silicates, bentonites, carbonates or bicarbonates.

Some of these extenders are themselves hydrophilic polymers and can as such for the production of articles according to the invention be used. Such hydrophilic polymers are hydroxypropyl methyl cellulose phthalate (HPMCP) polyvinyl acetate phthalate (PVAP), cellulose acetyl phthalate (CAP), acrylates and methacrylates, with Phthalic acid, succinic acid, or crotonic acid treated gelatin and shellac. These polymers are preferred when

Entero properties are desired. They preferably contain -25% water, particularly preferably 15-22% by weight, based on the water-containing polymer. _{HPMCP 7} PVAP and CAP, especially PVAP and CAP, are preferred. Most preferred, however, is PVAP, all of which are processed by injection molding and with a water content of 5-25%, preferably 15-21% by weight, based on the mixture.

Some of these polymers are not thermoplastic and it is therefore all the more surprising that they. processed in compression molding can be.

The processing temperature is in the range from 70 ° C to 190 ° C

5 2 and the pressure in the range from 600 to 3000 χ 10 N / m; where on known machines can be used.

A moldable starch mixture of corn, wheat, potato, rice and / or tapioca starch is preferred. The starch contains approx. up to 100% amylose and approx. 100 to 0% amylopectin, preferably 0 to 70% amylose and approx. 100-30% amylopectin. Particularly preferred is potato or corn starch.

In the following, the terms "starch" and "gelatin" also include Foams, modifications or derivatives of starch and gelatin and their combination with hydrophilic polymers, their properties for printing or Injection molding - especially for the production of capsules - are suitable.

The starch to be used has a water content of 5 - 25%, preferably 15-21% and particularly preferably 17-20% by weight based on the starch mixture. You can also use various additives such as plasticizers, lubricants, crosslinking agents and / or Contain dyes and extenders. For this purpose, the same compounds as described above for the hydrophilic polymers can be used, be used. The processing temperature for injection molding of

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Strength is between 80 and 240 C, with a pressure in

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Range from 600 to 3000 χ 10 N / m.

The water-containing starch, optionally containing further additives, is at these temperatures and pressures and in known injection molding machines processed in a manner known per se.

Articles according to the invention can also be produced by profile extrusion, Mold casting, vacuum forming, thermal forming, extrusion, casting in combination with vacuum forming. Injection molding is preferred, however.

The advantages of the present invention are further illustrated by the following detailed description.

Detailed description

The embodiments of the present invention can be classified into 3 groups.

1) Divisible or separable capsule

The divisible capsule can be swallowed whole or it can divided into parts that can be swallowed individually. For this reason, both the linked capsules and the separated pieces have a shape that can be swallowed easily and that can also indicate the area of application. Of the Body part or the cap part or both parts can be connected by a lamella. One embodiment of this group is in Fig. 1. 2. 3 and 4 are shown, which are a perspective view of a divisible capsule consisting of 2 units, each consisting of

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a cap part 2 and a body part l _f represents. As can be seen from FIG. 2, which shows a section along the line 2-2 of FIG. 1, the two body parts 1 are connected by a weak lamella 5. The two cap parts 2, however, are not connected. 3, which is a further view of FIG. 1, shows this dosage form after filling, or before the cap parts 2 are placed on the body parts 1. FIG. 4 is a side view of FIG. 3 after the cap parts 2 have been placed on the body parts 1. This embodiment according to FIGS. 1-4 can be swallowed as a whole capsule, or it can be divided along the lamella 5 into smaller units, which in turn can be swallowed individually. The two parts of the divisible capsule according to FIGS. 1-4 can be filled with different or with the same medicament. In the case of filling the same drug, the break-up halves the dose. However, if two different drugs are filled into the "two capsule parts, the desired combination can be swallowed by breaking the capsule at the lamella. To identify the contents of the two parts, the two parts can either be made in different colors or have different printing." The capsule parts 1 and 2 and the lamella 5 connecting them can be produced in one operation by pressure molding, preferably injection molding.

5 and 6 show a further embodiment of a capsule with 4 subdivisions. Fig. 5 is a plan view and Fig. 6 is a side view of Fig. 5 showing the 4 cap parts 2 and 4 body parts 1, which are connected to one another by a weak lamella 5 show. This capsule can be used as a whole or as the 4 parts be taken individually. The capsule parts or subdivisions can be filled with the same or different medicaments will. Further embodiments are shown in FIGS. 7 to 12. The numerical designations are the same as in Fig. 1-6. In this embodiment, the cap parts 2 are with the body parts 1 by weak connections as in

11 and 12 shown connected. The cap parts 2 can overlap the body parts 1. Next, the cap parts 2 of the Connection point of the lamella 5 have an indentation 6, so that the lamella even after breaking apart into individual parts is difficult to see.

Another embodiment is shown in Figs. 13 and 14, wherein the capsule consists of 3 parts, an inner and 2 have outer parts, each of which in turn consists of a body part 1 and a cap part 2. In Figs. 13 and 14 the outer parts are triangular in shape. On the other hand, the outer parts as shown in Figs. 15 and 16 can have a semicircular shape exhibit. According to the embodiments in FIGS. 13-16, only the body parts 1 are connected to lamellae 5, but the caps are Individual parts.

2) Divided capsules

This type of capsule has 2 or more compartments or chambers for Medication. They cannot be broken into smaller units, but they can be done with 2 or more different drugs are filled "that are to be swallowed at the same time. It is an advantage of the capsules according to the invention that the number of compartments or chambers does not have to be limited to 2, but can be adapted to the area of application.

An embodiment of this group is shown in FIGS. Fig. 17 shows an expanded perspective view a divided capsule with a body part 1 and a cap and with 2 chambers which are separated by a wall 5. Each of the Department or chambers contain a different drug. 18 shows a section of a compartmentalized capsule from FIG 17 along the line 18-18 in the closed state, wherein

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one the complete separation of the drugs of the subdivision or chambers clearly recognizes. 19 is a plan view of another divided capsule according to the present invention at which the two cap parts 2 axially abut one another at their open end. Fig. 20 is a section of Fig. 19 along the line Line 20-20, where the abutting of the caps 2 at their open ends can be clearly seen. Inside these caps 2 there is a cylindrical body part 1, which is separated into two chambers 11 and 12 by a cast-in plate or a partition 5 is separate and can accommodate different drugs. After the medication has been filled into the chambers 11 and 12, each of the two caps 1 telescopically from the open end over the body 1 pushed to enclose the various drugs in it. Can be used for various therapeutic needs one of the caps 1 consist of a material that is soluble in the acidic region of the gastric secretion. The other cap 1 and the Body part 2 can consist of an enteric material, in this way a medicament in a chamber in the stomach and the the other, which is in the other chamber, can only be dissolved in the intestine. By varying the materials and / or the Thickness of the caps 1 and of the body part 2 can be used to control the rate of dissolution of each of the two chambers 11 and 12 reach.

It is a further feature of the present invention that the cap part 1 and body part 2 are pushed into one another in this way that the surface at the overlap zone J, as in FIGS. 18, 19 and 20, is smooth.

3) capsule pack

A capsule pack consists of 2 or more capsules that are linked together so that they are divided into individual capsule units

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can be separated. These capsule packs are not intended to be swallowed whole, but rather represent a suitable one Storage form, for example, in the event that each unit is to be taken periodically.

The number of parts connected in total is not limited. Capsule packs can also be used to create divisible Combine group 1 capsules and group 2 compartmentalized capsules. An embodiment of this group is shown in Fig. 21 and 22 shown. Fig. 21 is a plan view showing the capsules lined up along their axis. Fig. 22 is a section of Fig. 21 along the line 22, wherein the connection of the capsule body 1 by the lamellae 5, which are made of the same material how the capsule body 1 exist and were obtained by simultaneous pressure forming recognizes. The cap parts 2 of the Capsule packs are not connected to each other. Both the body parts 1 and the cap parts 2 can be fitted with locking mechanisms be provided in order to obtain a separation-proof closure. Another embodiment of the capsule pack is shown in FIG Figs. 23 and 24 are shown. Fig. 23 is a plan view showing circular arrangement of the capsule units. Fig. 24 is a Section along the line 24-24 of FIG. 23, the capsule bodies 1 being connected to one another by the connecting pieces 5, the consist of the same material as the capsule body 1. These connecting pieces 5 are simultaneously with the capsule bodies manufactured. Both parts, i.e. the bodies 1 and the caps 2, can also be provided with locking mechanisms.

Another embodiment of the capsule pack is shown in Figures 25 and 26; it is used to combine 2 different Medication. FIG. 25 is a plan view showing the capsules hanging from the connector 5. Fig. 26 is a longitudinal section

the line 26-26 of Fig. 25 showing how capsule bodies 1 and Caps 2 can be produced at the same time without printing forms. The cap parts are not connected to each other. The capsules are in Arranged in 2 rows so that the 2 drugs can be filled into the body parts that are in contact with each other.

Press-through packs, so-called blister packs, are known for the packaging of pharmaceutical and other products that require high dosing accuracy. It's another feature of the present invention that hard-shell capsules from the blister pack components of a blister shell and a Cover sheet, which were welded with heat and pressure, can be produced after the blister shell with a Has filled drug. According to the invention, the press-through pack components Made from water soluble and edible hydrophilic polymers.

27 is a plan view of one embodiment of a Capsule blister pack, in which the blister sheet 10 different

Has subdivisions 11, 12, 13, 14. Fig. 28 is a section

along the line 28-28 of FIG. 27, the blister sheet 10 having been welded to the cover sheet 15 by means of pressure and heat and the Blister compartments 11, 12, 13, 14 ... have been sealed with the medication in them. »At the seam of the blister sheet 10 With the cover sheet 15, perforations 16 can be made for easier separation of the blister chambers 13, 14. Fig. 29, 30, 31 and 32 show other embodiments of capsule blister packs, using the same numerical designations as in FIG Figures 27 and 28 were used. 29 and 30 show capsule blister packs, the blister sheets 10 and the Cover sheet 15 have symmetrical subdivisions 13, 14. Figs. 31 and 32 show capsule blister packs each of which Unit 11 and 12 in “further chambers 17, 18, 19, 20 for inclusion different drugs.

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The present invention also includes the sealing and closing of the nested capsule parts. This Sealing provides further protection against separation and adulteration of the contents of the capsule, and makes the capsule additionally moisture and gas tight. Capsules according to the invention can be used for pharmaceutical purposes, but also for exact, quantitative dosing of dyes, chemicals, spices, Fertilizer combinations for plants, fertilizers with protective substances, seeds, cosmetics, agricultural products etc. serve.

Claims (9)

WARNER-LAMBERT Morris Plains PD 3140 Capsule Dosage Forms Claims 1. Divisible hard-shell capsule shapes, characterized in that that the individual capsule units, each consisting of a cap part and a body part, which fit into each other are slidable, are connected to one another in such a way that the individual capsule units are easily separated from one another can be .. 2. Hard-shell capsule packs according to claim 1, characterized in that the individual capsule units, each consisting of a cap part and a body part, which can be pushed into one another, are connected to one another in such a way that the individual capsule units can be easily separated from one another. 3. Hard-shell capsule shapes, consisting of a cap part and a body part, characterized in that the body part has a plurality of compartments. 4. Capsule units according to one of claims 1-3, characterized in that the capsules with lamellae are connected. 5. Capsule units according to one of the claims 1-4, characterized in that the body part and / or the Cap part is connected to a lamella or are. • Ζ ' 6. Kapselforitien according to one of the patent claims 1-5, thereby characterized in that it consists of a hydrophilic polymer or a mixture of such polymers with a water content of 5 - 25% (calculated on the hydrophilic water-containing polymer mixture) and where gelatin is used, it has a water content of 10-20% by weight (calculated on the water-containing gelatin mixture), and / or from starch or a starch mixture with a water content of 5 - 25% by weight (calculated on the water-based starch mixture), are manufactured by injection molding. 7. Capsule molds according to one of claims 1-6, characterized in that they are sealed. 8. Use of the capsule forms according to one of the claims 1 - 7, for the precise dosing of pharmaceuticals, dyes, Chemicals, spices, fertilizer combinations for plants, fertilizers with protective substances, seeds, cosmetics or agricultural products. 9. Capsule forms according to one of claims 1-7, the precisely dosed amounts of pharmaceuticals, dyes, chemicals, Contains spices, fertilizers, seeds, cosmetics, or agricultural products.