DE2834226A1 - Multilayer tabletting system for pharmaceutical prods. - with separate filler spaces and split bottom plunger - Google Patents

Abstract

Tablets with two different components, sepd. by a vertical central plane, are produced in eccentric or turntable presses by using separate filling devices for separate compartments created by split bottom plungers. The bottom plunger is split into two halves which are divided by a tongue. The two different mixes of granules are charged through a filling slipper with a partition. After withdrawal of the slipper the tongue is withdrawn flush to the top of the plunger and the top plunger can compress the tablet. An upward movement of the bottom plunger ejects the tablet from the die. The tablets have smaller contact areas between the different components than tablets with a horizontal subdivision. Both parts are kept clearly separate and there is less intermixing between them.

Description

Pressed body

Attention Wle V Vw ~ ~ and methods and apparatus for their manufacture Pressed body and methods and apparatus for their manufacture. The invention relates to new ones Pressed bodies, in particular tablets, which are essentially composed of juxtaposed Areas of different composition exist.

Multilayer tablets with horizontally stacked layers are known. The German Auslegeschrift 1 230 523 Already pointed out: They can only be produced with the help of a rotary tablet press those with several filling stations and a larger number of two or three-stage working stamps; in addition, the contact surface extends of the layers are horizontal over the entire diameter of the tablet and is accordingly very large.

To avoid these disadvantages, it was proposed there, multilayer tablets with vertical stratification, whereby in particular the filling funnel and filling shoe by one or subdivided several approximately vertical partitions in this way should be that these partitions end tightly closing at the bottom over the press die. This can be more vertical with different pressed material while maintaining it Separation areas between the different layers of the goods are filled.

Also those proposed with the help of the German Auslegeschrift 1 230 523 However, tablets available from the device still have certain disadvantages. So are the individual areas of the tablet are not clear without mixing their components separable from each other, because in the proposed method of manufacture none arise clean vertical surfaces, but mix the different powder mixtures in their limit area depending on their flowability and the other with the Manufacture parameters to be observed more or less with each other.

The invention was based on the object of avoiding these disadvantages., This The object was achieved by providing the compacts according to the invention and also one Method 'and' solved a device for their production.

It has been found that pressed bodies of the type described, whose individual areas can be clearly separated from one another without mixing their components can be obtained by not only using the filling devices in their manufacture (Funnel and filling shoes) divided by partitions, but also the filling spaces divided exactly in the dies by using vertically split pressing tools.

The invention relates to pressed bodies, essentially consisting of adjacent areas of different composition, thereby characterized in that the individual areas are clear without mixing their components are separable from each other.

The invention also relates to a method for production such a pressed body, which is characterized in that one in an eccentric or rotary machine precisely divides the filling spaces in the dies by (a) Slotted lower punch with vertical in the plane of separation of the lower punch pressed parts slidably arranged tongues or (b) vertically divided into slide elements Press rams, the pressed parts of which are arranged individually vertically displaceable from the outside are used and separate filling devices for filling the individual filling space areas begins.

The invention also relates to pressed bodies produced with Using the aforementioned procedure.

Finally, the subject matter of the invention is a device for production of the said compacts with the help of eccentric or rotary machines by dividing the filling spaces in the dies by (a) slotted lower punches with vertically displaceable arranged in the parting plane of the lower punch pressed parts Tongues or (b) press rams divided vertically into slide elements, their pressed parts are arranged individually vertically displaceable from the outside, and separate filling devices for filling the individual filling space areas.

The method according to the invention and the device according to the invention are based on Fig. 1a to le (variant (a)) - or. based on Fig. 2a to 2g (variant (b)) explained in more detail by way of example.

According to variant (a), the upper punch 1 is first of all a tablet machine raised. During the downward movement of the lower punch 2, the filling space is through vertical displacement of the tongue 3 divided into two sub-areas 4a and 4b, the outside of the die 5 are limited (Fig. 1a).

Now with the help of the filling shoe 6, the filling space by a Partition 7 is divided into two areas such that the partition closes tightly ends above the tongue, -two different molding compounds (granulates or powder mixtures) 8a and 8b filled into the two sub-areas 4a and 4b of the die filling space (Fig. 1b). After the filling is finished, the tongue 3 is pulled down (Fig. 1c), then the molding compounds by immersing the upper punch 1 to form a compressed material of two areas 9a and 9b arranged next to one another, compressed (FIG. 1d). By simultaneously lifting the lower punch 2 and tongue 3, the pressed body 10 (tablet) ejected and stripped with the scraper 11 (Fig. Le).

The method according to variant (b) proceeds in a similar manner, with a vertical the lower punch divided into slide elements 12a and 12b is used; slide in the process these slide elements on top of each other in the gap plane; First of all, this becomes a slide element 12b pulled down, creating a cavity 13b (Fig. 2a). This one is with the help of the filling shoe 14b, the bottom opening of which with one edge exactly at the punch separation cut completes, filled with the molding compound 15b (Fig. 2b). When the filling is finished by Moving the upper punch 1 and the slide element against one another 12b, a pre-compressed compressed material 16b is produced in the cavity 13b (FIG. 2c). Afterward a cavity 13a is created - quite analogously - after pulling down the slide element 12a, 16b being shielded by the cover 17b (FIG. 2d). The cavity 13a becomes filled with the molding compound 15a by means of the filling shoe 14a (FIG. 2e). Afterward is this together with the compressed material 16b in the pressing process (Fig. 2f) by dipping of the upper punch 1 and with the pressure roller 19 generated counter pressure of the lower punch press parts 12a and 12b, which now form a closed lower punch, to the desired Pressed body 20 with the desired thickness and strength pressed. The lower punch pressed parts are controlled via the control cams 18a and 18b (only shown in Fig. 2f). The pressed body 20 is then after lifting the upper punch 1 by common Lifting the lower punch press parts 12a and 12b and excavated with the scraper 11 stripped (Fig. 2g).

According to both variants, the compacts obtained can either directly or via a cleaning sieve drum, where they are deburred and cleaned in be directed to a collecting vessel.

Further variants of the method according to the invention can, for. B. in it exist that the upper stamps are slotted and provided with a tongue (Variant (a)) or that the upper punch is divided vertically into slide elements are (variant (b)); these embodiments enable the production of step-shaped Pressed body.

Furthermore - especially with poorly flowing molding compounds - the filling of the cavities by installing stirrers and similar auxiliary devices be improved or supported.

The control of the lower punch parts can be done in a manner known per se by curved segments, rods and other elements common in mechanical engineering. The movements can be adjusted to the requirements of the desired compact by adjusting drives be adjusted.

A particular advantage of variant (b) is that the individual Molding compounds can be dosed independently of one another; this is e.g. after the in the DE-AS 1-230 523 described method is not possible.

According to the invention, the term “pressed body” is to be used in the broadest sense to understand. It includes tablets, dragee cores and other compacts, as they are in the Galenics are common, but also compacts, such as those found in glass powder, Ceramic, plastic, food and luxury food industry as well as in the chemical Industry.

In detail, the new compacts according to the invention can be very diverse Own shapes. Some of these are sketched by way of example in FIGS. 3a to 3f. Pressed body consisting of two areas with a dividing groove (val. e.g.

3a) are preferred. Other embodiments consist of two Areas are shown in Figures 3b and 3d; these can also be easily combined with a additional dividing groove can be provided. 3c and 3f show embodiments, the three or two areas arranged next to one another according to the invention and additionally one horizontal layer below or above (top layer) own. The embodiment according to FIG. 3e shows three arranged side by side Areas of different thickness that are particularly easy to separate from one another.

In addition, the new pressed bodies can, for example, be round (circular or oval) or angular, have flat or curved surfaces, one or contain several (e.g. 2 or 3) additional top or intermediate layers.

The new tablets show old advantages of the well-known multilayer tablets, e.g. the spatial separation of physically or chemically incompatible substances or the usability as a matrix prolonged-release tablet with a quick-release initial layer. They also show the advantages of the known multilayer tablets with vertical Layering, e.g. small contact area and therefore extremely low interaction of areas that are incompatible with each other.

Compared to these, however, they can be dosed more precisely because the different Molding compounds (granules) flow independently of one another into separate chambers and so on each can be more easily adapted to the required processing conditions. In addition, the individual areas can be easily and cleanly separated from one another. This makes it possible for the first time to sequentially process the components of a single tablet and / or in various ways or unwanted portions of the tablet cancel before taking.

The new tablets can be used in many ways, e.g. for drug combinations, in which the effect of one component should set in particularly quickly (e.g. Combination lozenge and oral tablet, solution and oral tablet), and / or in which the active ingredients are poorly compatible with one another, and / or in which the active ingredients show different absorption optima (e.g. use before and after eating), and / or for day / night active ingredient combinations (e.g. antihistamines, Sedatives / narcotics), and / or for the combination of a drug with a Compatible excipient (this before or after the active ingredient is taken), or for forte / mite combinations. The invention also encompasses Tablets with stabilizing areas, e.g. with a desiccant area, which can be separated before use (e.g. for tablets with moisture-sensitive Active ingredients or for reagent tablets, e.g. enzyme tablets).

In many of these cases it has hitherto been customary (or only possible) the active ingredients in the form of a combination tablet at the same time or they in the form of different - also differently packaged - tablets at the same time or to take one at a time. In many cases, this procedure turned out to be not optimal; the new tablet offers a better solution.

Application examples: Example 1: Sublingual / peroral tablet Man prepares two granules of the following composition in the usual way: Granules 1: Granulate 2: isosorbide dinitrate 5 kg isosorbide dinitrate 15 kg sucrose 109 kg lactose 158.8 kg mannitol 80 kg corn starch 25 kg gum arabic 4 kg iron oxide pigment 0.2 kg stearic acid 2 kg magnesium stearate 1 kg 200 kg 200 kg Using any of the above Devices described is pressed from these granules tablets, which consist of two Ranges of 200 mg each according to FIG. 3a exist. One area is white and contains 5 mg of active ingredient, the other area is colored and contains 15 mg of active ingredient.

In the case of an acute attack of angina pectoris, it is swallowed colored part and then suck the white part of the tablet.

Example 2: Tablet, the active ingredients of which are poorly compatible with one another are.

Analogously to Example 1, two different granules are prepared and pressed from it tablets, the areas of which have the following composition: area 1: ascorbic acid 100 mg vitamin B 1 0.50 mg vitamin B 2. '' 0.75 mg vitamin B 6 1 nicotinic acid amide 7.25 mg rutin 5 mg lactose 95.50 mg corn starch 35 mg adipic acid 5 mg 250 mg Area 2: Vitamin A acetate dry powder 2 mg Vitamin B 12 preparation (1: 1000) 0.5 mg calcium D-pantothenate 2.5 mg vitamin D 3-cholesterol 0.0125 mg lactose 212.9875 mg microcrystalline cellulose 30 mg magnesium stearate 2 mg 250 mg The acid-sensitive Vitamins (area 2) are at a minimum of all acidic components (area 1) Separate boundary layer. - The tablet (both areas) can be taken at once will.

Example 3: Day / night tablet combination (antiallergic) analogously to Example 1, produce tablets with two areas of the following composition: area 1: Area 2: Brompheniramine 15 mg Brompheniramine 15 mg Lactose 153 mg Caffeine 50 mg talc 10 mg lactose 120 mg microcrystalline talc 14 mg cellulose. 20 mg magnesium stearate 1 mg dye 1 mg magnesium stearate 1 mg 200 mg 200 mg The white half (area 2) also contains caffeine because of the sedative side effects of bromopheniramine.

The colored half is taken in the evening, the white half in the morning.

Example 4: Tablet with moisture-sensitive active ingredients or auxiliaries Area 1: acetylsalicylic acid 500 mg ascorbic acid "500 mg sodium hydrogen carbonate 1000 mg citric acid 300 mg sucrose, finely powdered 175 mg stearic acid 249 mg Riboflavin 1 mg 2500 mg Area 2: calcium sulfate, anhydrous 620 mg calcium hydrogen phosphate, anhydrous 250 mg methyl cellulose 1 mg microcrystalline cellulose 59 mg talc 50 mg Magnesium stearate 20 mg 1000 mg Before use, the non-colored, the desiccant containing area 2 separated and discarded. Area 1 becomes like a normal one Effervescent tablet taken.

There is no "two-chamber seal" in the packaging of these tablets of tablet and desiccant (in the case of packaging in tubes), stopper with desiccant required, Example 5: Combination preparation against anxious agitating depression Area 1: Area 2: Lofepramine hydrochloride 38 mg oxazolam 20 mg ascorbic acid 10 mg lactose 155 mg lactose 179.5 mg starch 50 mg talc 20 mg methyl cellulose 2 m magnesium stearate 2.5 mg talc 20 mg magnesium stearate 2 mg iron oxide preparation 1 mg 250 mg 250 mg Depending on the symptoms, the combination of active ingredients with an overall constant ratio of active ingredients together or separately to different ones Times are taken.

Example 6: Tablet for determining phosphate Area 1: Area 2: Ammonium molybdate 1 mg ascorbic acid 1 mg sulfamic acid 2 mg sodium chloride 197 mg sodium chloride 193 mg adipic acid 2 mg adipic acid 4 mg 200 mg 200 mq The granules the composition mentioned are compressed in the known manner to form a tablet (Stamp engraving area 1: "1", area 2: "2").

Area 1 is dissolved in the medium to be analyzed by reaction Molybdophosphoric acid is formed quantitatively.

The reducing agent is then added (area 2).

Claims (5)

Claims: 1 pressed body, essentially consisting of side by side , / arranged areas of different composition, characterized that the individual areas are clear from one another without mixing their components are separable. 2. pressed body according to claim 1, consisting of two areas with a dividing groove. 3. A method for the production of pressed bodies according to claim 1, characterized characterized in that the filling spaces in an eccentric or rotary machine divides exactly in the matrices by a) slotted lower punches with vertical tongues displaceably arranged in the parting plane of the lower punch press parts or b) press rams divided vertically into slide elements, the pressed parts from the outside are arranged individually vertically displaceable, and used for filling the individual Filling space areas uses separate filling devices. 4. pressed body produced according to claim 3. 5. Apparatus for the production of pressed bodies according to claim 1 with Help from eccentric or rotary machines, characterized by precise division the filling spaces in the matrices by a) slotted lower punches with vertical in the parting plane of the lower punch pressed parts slidably arranged tongues or b) press rams divided vertically into slide elements, their pressed parts from the outside are arranged individually vertically displaceable, and separate filling devices for Filling of the individual filling space areas.