JPS6361928B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The subject of the invention is a divisible tablet with controlled and delayed release of active substances.

Dosage forms or slow-acting forms of orally administered medicines that control and delay the release of active substances in the body, especially in the blood circulation, in order to last as long as possible and keep a constant active substance concentration as they were, are old. known from. In that case, a coating is provided which controls and retards the release of the active substance, or at least a part of the carrier material and/or auxiliary substance in which the active substance is distributed is retarded. Tablets and capsules that allow controlled release of the active substance are the issue.

Tablets with grooves which make it possible to subdivide the medicament more or less easily into doses containing substantially equal amounts of active substance can likewise be used. By installing a relatively deep groove it is possible to cause easier disintegration of the corresponding tablet and to keep the dose as accurate as possible in the groove piece. In this regard, for example, US Patent No.
No. 3883647, U.S. (Design) Patent No. 201497, No.
202467 and German Patent Publication No. 1200790. Furthermore, slow-release tablets, approximately oval in shape, with cracks of moderate depth are also commercially available.

However, in the case of tablets in which the release of the active substance is delayed and controlled, e.g. with the splitting of the aforementioned splittable slow-release tablets, the surface of the tablet and with it also the surface of the dispensing portion may also be essentially free of cracks, e.g. By increasing the surface area by more than 20%,
Subdivision into crack groove pieces has disadvantageous consequences. The properties of the active substance release for the split groove pieces are therefore significantly influenced compared to the properties of the entire tablet. Experiments have shown how the delayed, controlled release of the active substance of a complete tablet changes due to the essentially increased total surface area due to splitting, and the split groove pieces no longer have this property or It turns out that there is only a small amount of it. Furthermore, in the case of cracking tablets with a coating that controls the release of the active substance, a relatively large portion of this coating falls off, so that a portion of the active substance is released in a more or less uncontrolled manner.

The problem that arises here, therefore, is that such fibers can be easily divided into groove pieces, each of which has approximately the same active substance content and has active substance release characteristics close to that exhibited by a complete tablet. The goal was to find a slow-release tablet that could be divided. That is, it was necessary to find a tablet shape that minimizes the increase in total surface area as much as possible due to the formation of crack grooves on the surface during division. In addition to this,
It should also be noted that such tablet forms are always manufactured, processed, packaged and unpacked easily and with the least possible damage. In this case, the following should also be taken into consideration: Thus, for example, in the case of blister packing, which is preferred for mechanical packaging, tablets with a smooth surface, obtained for example by coating with or without properties that control the release of the active substance, Due to their high smoothness, they are inherently easier to handle than, for example, tablets with a rough surface without such a coating. That is, the divisible slow-release tablet can, if desired, retain the lacquering process for coating in a manner that is as scratch-free as possible.

The release of the active substance as hereinafter defined is controlled;
Delayed splittable tablets can now yield fragments whose active substance release properties do not differ significantly compared to those of complete tablets, and the additional requirements mentioned above are likewise met. It was discovered. The tablet of the present invention has the following characteristics. i.e. ``an optionally coated and optionally one or more vertical layers of an auxiliary agent composition which causes a delayed and controlled release of the active substance. It consists of a rectangular compact made of at least one active substance in an auxiliary composition which may also contain additional and optionally active substances arranged, the rectangle having a height relative to The length to width ratio is approximately 2.5 to 5: approximately 0.9
~2:1, and the width is at most 2/3 of the length, and there are one or more fissure grooves running perpendicular to the length and height, the total depth of which is about 1/3 to about 1/2 of the height, but at least it is such a number that the product of the groove surface area and the number of possible groove pieces is at most 15% of the undivided tablet surface area. and the bottom and top surfaces are independently flat or curved convexly around the longitudinal axis or a line parallel to this axis, the side surfaces are flat, and the front surface can be shaped into any shape. characterized in that it consists of such a compact, the edges being tapered or rounded as the case may be.

The dosage unit form according to the invention satisfies the needs made for divisible tablets as well as slow-release tablets. That is because this dosage unit form has a surface area of more than 15% with two possible fragments and about 20% more with three such fragments compared to the surface area of an undivided tablet. by being easily broken into pieces with substantially the same or different predetermined active substance contents without increasing the total surface area. It has been established that the reduction in the retardation effect on the fractures is smaller than it would have been expected on the basis of the increased total surface area of porous fractures with irregular structures. That's surprising. These facts make it possible to carry out the treatment with divided tablets as precisely as with whole tablets, with regard to dosage and release of active substance.

The divisible slow-release tablet of the present invention has surprisingly high hardness despite its rectangular shape and relatively deep crack grooves, which are expected to be difficult to process and handle. It became even clearer that there was. This makes it possible, for example, to apply a coating to the divisible slow-release tablets of the present invention, which considerably avoids the formation of flaws, which coating not only facilitates the processing of the tablets, but also particularly during packaging. and makes it possible to provide the tablet with additional firmness, which is useful, for example, when extruding from a blister packing.

Furthermore, this surprising high degree of firmness and rectangular shape, which can optionally be enhanced by coating, is still in addition to the splittable slow-release tablets of the present invention. It has advantages. This tablet can thus be marked by embossment or printing, and on both sides, for example with the name of the manufacturer on one side and the trade name and/or code symbol for the drug on the other side. be able to. Moreover, the tablets of the invention are easy to swallow, both whole and in the form of pieces, ie they are substantially easier to swallow than round or oval tablets or their pieces. Furthermore, divisible multilayer slow-release tablets with different active substances and/or different active substance releases can also be made. In this case, certain layers can be arranged in such a way that the tablet does not have a disintegration point upon disintegration.

The divisible tablets of the present invention, as well as their corresponding compressed products, can be generally and simply described by the term "rod-shaped". This is because their parallel sides (webs) represent small rods with an approximately rectangular or approximately round cross section. The first type of compact is rod-shaped or biplanar in the narrow sense, in which the bottom and top surfaces define the height, usually the smallest dimension of the tablet, and the width, usually the intermediate dimension of the tablet. The two surfaces are planes, that is, the corresponding surfaces are parallel to each other and are usually the same. Such tablets or corresponding compressed products are later referred to as rod-shaped biplanes. The two faces defining the height as the smallest or sometimes intermediate dimension are curved convexly around a longitudinal axis or a line parallel to this axis, and both sides are always plane or parallel to each other Such compresses or tablets can be marked as "capsule-shaped". Eventually, this type was named capsule-shaped biconvex. This last type of compact is particularly suitable for the production of corresponding film dragees, ie for film coating. The edges of compressed products or tablets, especially rod-shaped tablets, are usually beveled or rounded. The surface of the so-called ridge, which forms from the matrix wall during the compression process, stands out particularly easily from that of the tablet, which forms from the cap of the stamp. Mixed shapes, e.g. with a flat bottom and a convexly curved top, are particularly conceivable for layered tablets, but in some cases the bottom may have no or only slight cracking depth. It only has . The front surface can be made in any shape, but it corresponds to the web created by the walls of the matrix and is convex, from the point of view of ease of manufacture on the one hand and ease of swallowing the tablet on the other hand. , from the middle part curved around a line parallel to the longitudinal axis,
However, at least one part consists of an approximately spherical arched lower and upper part.

The length to height ratio is about 3:1 to 4.5:1 and the width to height ratio is about 1 to 1.6:1.
In particular, a ratio of about 1.2 to 1.4:1 is preferred. However, it is preferred that the width is about 1/4 to 1/2 of the length.

The splittable slow-release tablet of the present invention has one or more crack grooves on one or both sides running perpendicular to the height and length, i.e. diagonally to the length. ing. In this case, it is preferred that the grooves applied on both sides are opposite, but can also intersect and also have the same or different depths. The tablet can thus be broken down into two or more predetermined identical or possibly different parts, for example depending on whether it is to be taken in the morning or in the evening. This allows individual and precise dosing of the drug, adapted to the requirements, i.e., the medical condition and the patient. The depth of the crack groove on one side or the total depth of the crack grooves attached to both sides is preferably about 2/5 to about 1/2 of the height of the tablet, in which case it is made by stamping. The cracks do not reach the web formed by the matrix wall or the flat sides of the tablet. Preferably, the sides of the split groove are beveled or arched. By splitting, the surface area of such a tablet can range from up to about 8 to about 12 if it can be broken into two pieces.
%, or up to about 11 if it can be broken down into 3 pieces
Increases by ~16%.

The divisible slow-release tablets according to the invention usually contain auxiliaries matched to the active substance used. Due to the high degree of disintegration and capping of the tablet, it is strongly bonded to the matrix to ensure a delayed and controlled release of the active substance. Preference is given to using auxiliary mass.

The matrix material which produces the delayed and controlled release of the active substance consists primarily of auxiliaries or auxiliary mixtures which are themselves inert or indigestible, such as polyvinyl chloride, acrylates and methacrylates. Consists of man-made substances. However, during its passage from the stomach to the intestines, it is overcome by the advancing softening effects (e.g. hydrophilic gel-forming agents) or the erosive effects (e.g. lipids or digestible di- and triglycerides in a mixture with an inert carrier). ).

As retarding auxiliaries it is possible to use essentially water-insoluble auxiliaries or mixtures thereof. Examples include fatty alcohols such as cetyl alcohol, stearyl alcohol and cetostearyl alcohol, and glycerides such as glycerin monostearate or mono-, di- and triglycerides of vegetable oils, and hydrogenated oils such as hydrogenated castor oil. or hydrogenated cottonseed oil, waxes such as beeswax or carnauba wax, solid hydrocarbons such as paraffin or earth's wax, fatty acids such as stearic acid, certain cellulose derivatives such as ethylcellulose or acetylcellulose, polymers or polymers. Examples of polymers include polyalkylenes such as polyethylene, polyvinyl compounds such as polyvinyl chloride or polyvinyl acetate and vinyl chloride-vinyl acetate copolymers and copolymers with crotonic acid, or polymers and copolymers of acrylates and methacrylates. For example, a copolymer of acrylic acid ethyl ester and methacrylic acid methyl ester is used. Auxiliaries which are water-soluble or water-swollen and which retard the release of the active substance are suitable intermediate cellulose derivatives, especially corresponding ethers such as methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose or sodium carboxymethylcellulose. (preferably, the compound has a relatively high viscosity), certain polymers such as polyacrylic acid and its salts, natural (anionic) mucilage substances such as xanthenes, gums, guar gum, tragacanth or alginic acid. and its salts.

The release of active substances that do not have particularly good solubility in the neutral intestinal environment, but have very good solubility in the acidic gastric zone, can be achieved by additions with functional carboxyl groups that dissolve in the neutral region. It can also be delayed by agents such as silica, cellulose esters such as cellulose acetate phthalate or hydroxypropylmethylcellulose phthalate or half esters of maleic anhydride copolymers.

The tablets of the invention in divisible slow-release form are prepared by adding fillers and carriers which do not have a critical influence on the release of the active substance, such as bentonite (aluminium oxide/silicon oxide), other than auxiliaries which delay and control the release of the active substance. hydrate), talc, dicalcium and tricalcium phosphates, lactose, silicic acid, cellulose and similar auxiliaries.

The divisible slow-release auxiliary agents of the present invention are used in addition to one or more active substances in the auxiliary composition to delay and control the release of the active substance and, if desired, to release normally, i.e. It can contain one or more active substances whose release is not delayed.
Such active agent or all such active agents will generally be different from the delayed-release first active agent, but may alternatively be the same as the first active agent. Usually such active substances are embedded in customary auxiliaries or preferably mixtures of customary auxiliaries, such as fillers, disintegrants, binders and lubricants. The fillers which usually form the internal phase of the granules are inter alia sugars such as lactose, starches such as corn starch, phosphates such as di- or tricalcium phosphates, cellulose (usually microcrystalline cellulose) or its like. derivatives, etc. Disintegrants forming the external phase of the granules are starches such as corn starch or derivatives thereof such as sodium carboxymethyl starch, cellulose (eg microcrystalline cellulose) or derivatives thereof such as ethers thereof, such as sodium carboxymethyl cellulose. The binder is a starch paste, gelatin, a cellulose derivative such as methyl cellulose, while the lubricant is a starch starch paste, gelatin, a cellulose derivative such as methylcellulose, while the lubricant is a material such as stearic acid or a suitable salt thereof such as magnesium stearate or calcium stearate, talc, colloidal silicon oxide, etc. be.

For the release of different types of active substance, the divisible slow-release tablets of the invention with several, e.g. two, tablet compositions contain these compositions in different layers, and this layer run parallel to the plane defined by the longitudinal direction of the tablet, i.e. the length and width directions, in order to ensure a uniform content of active substance in the fragments. As already mentioned, the splittable slow-release tablet of the present invention exhibits a surprisingly high strength, without impairing the tablet's ability to be split.
This makes it possible to provide the finished tablet with a coating which gives it additionally increased strength.
In addition, coating may be necessary if the active substance has an unpleasant taste, especially a bitter taste, which serves to mask the taste and thus makes the tablet easier to swallow.

This coating is usually a soluble film coating that does not have any effect on the release of the active substance. Soluble film coating has a thickness of approx.
It is 20 μm to 100 μm.

Particularly suitable as film coating materials are soluble cellulose derivatives such as cellulose ethers, such as methylmolulose, hydroxypropylcellulose or especially hydroxypropylmethylcellulose, mixtures of polyvinylpyrrolidone or combinations of polyvinylpyrrolidone and polyvinyl acetate with hydroxypropylmethylcellulose. A mixture of polymers, a mixture of Sielac and hydroxypropylmethylcellulose, polyvinyl acetate or its copolymer with polyvinylpyrrolidone, or a mixture of water-soluble cellulose derivatives, such as hydroxypropylmethylcellulose, and water-soluble ethylcellulose. These actual coating agents can be used, if desired, in mixtures with other auxiliaries such as talc, lubricants such as polysorbates (for example to facilitate dosing) or pigments (for example for marking purposes). You can also do it. These coatings can be applied in aqueous solutions or in organic solvents (for example solutions containing Sierra or ethylcellulose in the organic solvent) depending on the solubility of their constituents. Furthermore, acrylates which are themselves water-soluble, such as copolymers of ethyl acrylate and methyl methacrylate, which are used in aqueous dispersions, and water-soluble auxiliaries, such as lactose, polyvinylpyrrolidone, polyethylene glycol or hydroxypropyl methylcellulose, can also be used. Mixtures can also be used.

The preparation of a tablet composition according to the invention, consisting of an active substance and an auxiliary composition comprising auxiliaries, both those having the effect of delaying and controlling the release of the active substance and those for the normal release of the active substance, The process is carried out in the usual manner, for example by making the granules and, if necessary, adding suitable auxiliaries and using the customary mixing, compacting and coating equipment. For example, in the case of a two-layer tablet in which the layers release different types of active substance, first of all the lower half of the tablet, which has the property of delaying the release of the active substance, for example, is pressed first and then pressed onto this. For example, it is common to press the upper half of a second tablet that normally releases the active substance and then press the two-layer tablets together to form the finished product.

The active substance is optionally coated and contains the active substance in an auxiliary composition that delays and controls the release of the active substance or in two different layers. , consisting of a compact containing the active substance in the controlling auxiliary composition and a second active substance in the auxiliary composition that does not significantly influence the release of the active substance, the shape of the compact being within the range of length and width. and height is 3-4.5:1-1.6:1, and either one or two crack grooves are present opposite each other and run perpendicular to the length and height. , the sum of its depths being about 2/5 to about 1/2 of the height of the tablet, and other shape features corresponding to the above shapes, but in the above sense capsule-shaped. Particularly preferred are such divisible slow-release tablets. When a tablet having the above dimensional ratios is divided, the total surface area of the fragments increases by about 8% to about 12% compared to the total surface area of the undivided tablet. Auxiliary compositions for delaying and controlling the release of the active substance are polymers or copolymers with retarding properties, in particular polymers or copolymers of acrylates or methacrylates, such as copolymers of ethyl acrylate and methyl methacrylate. Contains an auxiliary agent consisting of.

The composition of this new divisible slow-release tablet according to the invention and its manufacture are described in detail, inter alia, in the following examples.

The accompanying drawings illustrate examples of various shapes of divisible slow-release tablets of the present invention. FIG. 1 shows a rod-shaped tablet with two planes, which has grooves on both sides [1a: front view, 1b: side view, 1
c: Plan view, x: length, y: width, (a: web),
z: height (usually the smallest dimension)] and can be split into two identical pieces. Figure 2 shows a capsule-shaped two-sided convex splittable slow-release tablet, which is slotted on both sides, coated with coating b, and split into two identical pieces. (2a: Front sectional view, 2b:
Side view, 2c: top view). Figure 3 shows various front views of tablets of the invention. 3a with a notch on one side or 3b with a notch on both sides, a two-layer, capsule-shaped, double-sided convex splittable slow-release tablet, in which, for example, layer c is It has the property of delaying and controlling the release of the active substance, whereas the active substance is released from layer b without being delayed or controlled. A capsule-shaped slow-release tablet 3c with convex surfaces, which can be divided into three pieces, and has dividing notches on both sides. Capsule-shaped slow-release tablet 3d with two convex sides, which can be divided into two pieces of unequal size, and one notch for dividing is attached on one side It is being A capsule-shaped delayed-release tablet 3e with convex surfaces can be divided into three pieces, and staggered dividing notches are attached to both sides.

Example 1 1-[4-(2-methoxyethyl)phenoxy]
-3-isopropylaminopropan-2-ol (metoprolol) tartrate 2.0
Kg, colloidal silicon dioxide 0.1Kg, calcium hydrogen phosphate 0.2Kg and microcrystalline cellulose
0.25 Kg of the mixture is granulated in a fluidized bed using 0.6 Kg of a 30% aqueous suspension of a 70:30 copolymer of ethyl acrylate and methyl methacrylate. The spraying rate is 300ml/min with air supply at 30°C. Drying is then carried out in the same apparatus for 20 minutes while supplying air at 40°C. Put the granules into a planetary mixer;
Add 0.8 kg of stearyl alcohol, melted and heated to 60°C, and knead the whole thing for 15 minutes. After cooling,
The granules are pressed through a 1 mm mesh width sieve and mixed for 10 minutes with 0.05 Kg of colloidal silicon dioxide and 0.4 Kg of hydroxypropyl methylcellulose (viscosity 15000 cps) in a tumbler mixer.

The slow-release granules thus obtained were pressed to produce capsule-shaped double-sided convex slow-release tablets each having a total weight of 445 mg using a guiding die with the following dimensions: Perform on a tablet press. Its dimensions are length 17.0 mm, width 8.0 mm and radius of curvature 4.8 mm, and one of the two opposing dies has a height of 2.0 mm (with respect to the depth of the recess)
and includes a wedge forming a tapered dividing notch (wedge angle: 45° to 60°), or two opposing dies each having a height of 1.1 to form the desired dividing notch. It has a wedge of mm (in terms of the depth of the recess). The overall height of the compacted body produced is approximately 4.6 mm.

The coating is carried out in a 55 cm diameter coaching vessel equipped with a baffle. With the aid of a two-component nozzle, 5 kg of the compress are sprayed continuously with the coating solution or suspension of the following composition. Hydroxypropyl methylcellulose (viscosity 5 cps) is dissolved in 1.2 kg of demineralized water. to this,
Titanium dioxide 20% in a solution of 0.005Kg polysorbate 80, 0.05Kg talc and 0.007Kg hydroxypropyl methylcellulose in 90% ethanol
Add a homogeneous suspension of The temperature of the supplied air is maintained at 60°C, and the temperature of the compressed material inside the container is maintained at approximately 35°C. The amount of film coating sprayed is 19 mg (dry weight) per compact.

The dissolution rate of film-coated tablets is
Diameter method: (Langenbucher
and Rettig, Drug.Dev.Ind.Pharm., 3 , 241,
1977) using simulated gastric fluid (PH 1.2, no enzymes present) at 37°C for the first hour and then using simulated intestinal fluid (PH 7.5, enzymes absent) 16
Measured at flow rate in ml/min. The following results were obtained for the release of active substance from whole and half tablets of film-coated tablets as % of theoretical content:

Time Whole tablet Half tablet 60 minutes 23% 27% 120 minutes 38% 43% 240 minutes 57% 65% 360 minutes 72% 78% Example 2 1-[4-(2-methoxyethyl)phenoxy]
- Delayed granules of the tartrate salt of 3-isopropylaminopropylaminopropan-2-ol (metoprolol) are made as described in Example 1.

The following non-delayed-release granules are made at the same time.

3-(4-chloro-3-sulfamoylphenyl)-3-hydroxy-isoindolin-1-one (chlortalidone) 0.25Kg, lactose
A mixture of 1.75 Kg and 0.5 Kg of corn starch is processed into a plastic mass in a planetary mixer with a paste consisting of 0.1 Kg of corn starch and 0.2 Kg of water. The moist octopus mass is forced through a 2 mm mesh width sieve and dried in a fluidized bed at 60° C. for 20 minutes. The dried granules forced through a 1 mm mesh width sieve are mixed with 0.1 Kg talc, 0.01 Kg magnesium stearate and 0.29 Kg microcrystalline cellulose.

Pressing these two types of granules to make a capsule-shaped double-sided convex tablet is called a layer tablet.
This is done on a tablet machine with a guiding die that allows for the production of tablets. First weigh in the non-slow release granules, then add the slow release granules from a separate charge. To press, press 2 against 2 different dividing notches.
Two dice are used, the dimensions of which are as follows: Length 19.0mm, width 7.0mm and radius of curvature 4.2mm.
The tapered dividing notch in the compressed body is
The depth (depth of the recess) on the slow-acting layer side is
1.7 mm and the depth on the side of the chlorthalidone layer is 0.8 mm. Tablets with a height of approximately 6 mm are produced.

The release of metoprolol tartrate from the slow release layer occurs as described in Example 1. The disintegration time of the non-delayed chlorthalidone layer is 2-3 minutes (USP disintegration test device, simulated gastric fluid 37°).

Example 3 Milled hydrochloride salt of 1-(2-allyloxyphenoxy)-3-isopropylaminopropan-2-ol (oxprenolol) 9.6
A mixture of 6.98 Kg of ground lactose and 16.0 Kg of a 30% aqueous dispersion of a 70:30 copolymer of ethyl acrylate and methyl methacrylate is granulated in a fluidized bed. The spray speed is
At 0.7/min the temperature of the supply air is 38°C. The mixture is then dried in the same apparatus for 25 minutes while supplying air at 40°C. 0.12 Kg colloidal silicon dioxide, 0.3 Kg calcium stearate and 4.0 Kg stearic acid are added simultaneously and the granules are forced through a 1 mm mesh width sieve and then mixed for 15 minutes in a planetary mixer.

Pressing these granules to produce capsule-shaped double-sided convex tablets with a grain size of 410 mg each requires a guiding die (the two opposing dies are separated) with the following dimensions: The process is carried out on a tablet press equipped with a wedge (with a wedge to form a notch). Its dimensions are length 16.5mm,
The width is 6.0mm and the radius of curvature is 3.6mm. The tapered dividing notches on both sides are each 1.47 mm deep and the height of the compact is approximately 5.4 mm.

The compact thus obtained is coated into a film as described in Example 1.

The rate of dissolution was determined by the method described in Example 1 and gave the following results.

Time Whole tablet Half tablet 60 minutes 32% 36% 180 minutes 62% 68% 300 minutes 80% 86% 420 minutes 92% 96% Example 4 3-(2-allyloxyphenoxy)-3-isopropylaminopropane-2 - Delayed release granules of ol(oxprenolol) hydrochloride are made as described in Example 3.

At the same time, conventional granules are made as follows.

3-(4-chloro-3-sulfamoylphenyl)-3-hydroxy-isoindolin-1-one (chlorthalidone) 15.6Kg, microcrystalline cellulose 3.0Kg, dicalcium phosphate 6.456Kg, corn starch 0.9Kg , iron yellow 0.024Kg
and 0.120Kg of magnesium stearate are mixed homogeneously.

The pressing of the two active substance mixtures to form capsule-shaped tablets is carried out as described in Example 2. This tablet is 18.0mm long, 5.5mm wide, and about 5.6mm high.
mm and a radius of curvature of 3.5 mm, and the depth of the dividing notch on both sides is 1.47 mm in each case.

The release of oxprenolol hydrochloride occurs as described in Example 3, but the disintegration time of the non-delayed chlorthalidone layer is approximately 1-2 minutes (at 37°C using a USP disintegration test apparatus). (with artificial gastric juice).

[Brief explanation of drawings]

FIG. 1 is a front view, side view, and plan view of one embodiment of the tablet of the present invention, FIG. 2 is a front sectional view, side view, and plan view of another embodiment, and FIG. 3 is a further another embodiment. FIG. 3 is a side view of various embodiments of the invention.

Claims (1)

Claims: 1. An auxiliary composition, optionally coated, and optionally one or more columns, which causes a delayed and controlled release of the active substance. consisting of rectangular compacts made of at least one active substance in an auxiliary composition, which may contain additional and optionally active substances, arranged in layers; A rectangle has a length to height ratio of approximately (2.5 to 5): approximately (0.9 to 2): (1), and the width is at most 2/3 of the length, and the length and height There are one or more relatively deep crack grooves running perpendicular to the groove, the total depth of which is about 1/3 to about 1/2 of the height, but at least it is equal to the groove surface area. The number of grooves is such that the product with the number of possible grooves is at most 15% of the undivided tablet surface area, and the bottom and top surfaces are independently planar or have a longitudinal axis or a line parallel to this axis. convexly curved around, the sides are flat, the front surface is arbitrarily shaped, and the edges are sometimes beveled or rounded,
A divisible tablet for controlling and delaying the release of active substances, characterized in that it consists of such a compressed product as described above. 2. An auxiliary composition, optionally coated, and causing a delayed and controlled release of the active substance and optionally additional and active substances arranged in vertical layers. It consists of a rectangular compact made of one active substance in an auxiliary composition that does not essentially influence the release of the active substance, the rectangle having a length to height ratio of width to height. It is about 3-4.5:1-1.6:1,
The width is at most about 1/4 to 1/2 of the length, and there are one or more fissure grooves running perpendicular to the length and height, the total depth of which 2. The tablet according to item 1, which is made of the compressed product as described above, and has the same shape as described in item 1 above. 3 made up of one active substance in an auxiliary composition, possibly coated, and giving rise to a delayed and controlled release of the active substance, and in the form according to paragraph 2 above; The tablet according to item 2 above, which is made of a compressed product having the following characteristics. 4, optionally coated, and containing additional and active substances arranged in vertical layers and an auxiliary composition giving rise to a delayed and controlled release of the active substance; 2. A tablet according to claim 2, consisting of a compressed product made of one active substance in an auxiliary composition which does not essentially influence the release of the substance and having the shape characteristics described in claim 2. 5 Any one of the preceding paragraphs 2, 3 and 4, where the bottom and top surfaces of the tablet are flat and parallel to each other.
Tablets listed in section. 6. The tablet according to any one of the preceding items 2, 3 and 4, wherein the bottom and top surfaces of the tablet are curved in a convex manner around a vertical axis or a line parallel to this axis. 7. According to any one of the preceding paragraphs, the auxiliary composition causing a delayed and controlled release of the active substance is a polymer or a copolymer and contains an auxiliary agent with retarding properties. Tablets listed.