METHOD OF TABLETING, DEVICE FOR TABLETING AND SET FOR TABLETING

Abstract

The first object of the invention is a method of tableting a tablet mass comprising components crystallizing in a tetrahedral and/or regular system and/or subjected to micronization or nanonization, carried out in the following steps: moving the punches, filling the die cavities and/or die cavity with a tablet mass, lowering the punches and/or punch and compressing a tablet mass, pushing the tablets and/or tablet out of the die cavity, pushing the tablets and/or tablet out of the die, characterized in that the pressure in the tablet press chamber is lowered in the range from −0.005 MPa to −0.15 MPa, wherein the lowering of the pressure in the tablet press chamber reduces the pressure in the tablet press die cavity. The second object of the invention is a device for tableting a tablet mass. Another object of the invention is a kit comprising a tablet mass tableting device, as defined in the second aspect of the invention, and a vacuum pump.

Claims

1. A method of tableting a tablet mass containing components crystallizing in a tetrahedral and/or regular arrangement and/or subjected to micronization and/or nanonization, carried out in the following steps: a) moving the punch and/or punches, b) filling the cavity and/or die cavity with a tablet mass, c) lowering the punches and/or punch and compressing a tablet mass, d) pushing the tablets and/or tablet out of the cavity, e) pushing the tablets and/or tablet out of the die; characterized in that in steps b) and c) the pressure in the vacuum chamber (7, 13) is lowered in the range from −0.005 MPa to −0.15 MPa, wherein the lowering of the pressure in the vacuum chamber (7, 13) reduces the pressure in the tablet press die cavity.

2. The method according to claim 1 characterized in that in steps b) and c) the pressure in the external vacuum chamber (13) is reduced.

3. The method according to claim 1, characterized in that the tablet press is selected from the group comprising: a single-punch tablet press or a rotary tablet press.

4. The method according to claim 1 characterized in that the tablet mass is selected from the group comprising: polysaccharide, preferably microcrystalline microcellulose, naturally derived silica, preferably diatomaceous earth, crystalline active substance, preferably diosmin or micronized diosmin, a vitamin preparation, preferably vitamin D3 coated with hydroxyapatite.

5. The method according to claim 1, characterized in that the tablets have a thickness from 2.2 mm to 8.1 mm.

6. The method according to claim 1, characterized in that the pressure is reduced from −0.01 MPa to −0.15 MPa.

7. A tablet mass tableting device comprising a housing and a tableting mechanism, wherein the housing has a bottom wall, a top wall and four side walls that are connected to each other to form a sealed vacuum chamber, and the tableting mechanism is housed in the chamber housing, characterized in that a valve for connecting the vacuum pump (9, 12) is provided on the side wall (A3, B3) of the vacuum chamber (9, 12).

8. The device according to claim 7, characterized in that the tableting mechanism is a single-punch tablet press or a rotary tablet press.

9. The device according to claim 7, characterized in that the vacuum chamber (7) comprises a single-punch tablet press having a lower punch table (2) on which a lower punch (11) is placed, the chamber (7) and the tablet press die (5), wherein the die (5) is placed on top of the lower punch (11) and includes a die cavity (4) for introducing the upper punch (1) in order to introduce the tablet mass therein and to receive the upper punch (1).

10. The device according to claim 7, characterized in that the top wall (A1) of the vacuum chamber (7) comprises a die (5) of a single-punch tablet press.

11. The device according to claim 7, characterized in that the chamber (7) with the tableting mechanism, which is a single-punch tablet press, is placed in an external vacuum chamber which includes a vacuum valve (12) for connecting a vacuum pump.

12. The device according to claim 7, characterized in that the external vacuum chamber (13) comprises a rotary tablet press having a rotary tablet press base (16) placed on the bottom wall (B2) of the vacuum chamber (13), connected to a drive motor (6), and connected with the table via the rotary tablet press die (15), above which there is the upper punch (14) of the rotary tablet press.

13. A kit comprising a tablet mass tableting device as defined in claim 7 and a vacuum pump that is connected to the device via the vacuum valve (3).

14. The kit according to claim 13, characterized in that the device is placed in the external vacuum chamber (13) and a vacuum pump is connected to the external chamber (13) via the vacuum valve (12).

Description

[0031] Embodiments of the invention have been illustrated in the drawing, which shows

[0032] in FIG. 1 the device construction with the possibility of reducing the pressure in the chamber containing a single-punch tablet press,

[0033] in FIG. 2 the device construction with the possibility of reducing the pressure in the vicinity of a single-punch tablet press,

[0034] in FIG. 3 the device construction with the possibility of reducing the pressure in the vicinity of a rotary tablet press.

EXAMPLE 1 TABLETING METHOD

[0035] The vacuum chamber 7 or 13 comprises a tableting mechanism which may be a single-punch tablet press or a rotary tablet press. In the case of single-punch tablet press, it can first be placed in the vacuum chamber 7, and then placed together with the vacuum chamber 7 in the external vacuum chamber 13. Thereafter, the tableting mass is introduced into the tablet press cavity from the hopper 8 and the pressure is lowered, in chamber 7 or chambers 7 and 13, so as to achieve the desired tablet thickness in the range from −0.005 MPa to −0.15 MPa and the tablet mass is compressed. Examples of obtaining different tablet thickness are shown in the following embodiments. The compressed tablet is then ejected from the tablet press die cavity. The process can be carried out in a single-punch tablet press (FIG. 1 or FIG. 2) and a rotary tablet press (FIG. 3). As a consequence, when the upper punch enters the filled in die, increased contact points between the granulate grains are observed. The exhausted air leads to a reduction in the number of places where the surface tension is reduced, thanks to which the contact of the grafted material is much greater. With a further increase of the upper punch pressure force, increased deformation occurs—grains distortion. The energy loss occurring during this process will be lower than in the traditional process. This is due to the reduction of the frictional forces between the grains of the powder or granules or the friction between the side surface of the tablet and the die wall. Additionally, the reduction of the friction force results from the reduced amount of air in the tablet die chamber (4, 15), i.e. from the smaller amount of air particles adsorbed on the surface of the granulate or tablet mass.

EXAMPLE 2 TABLETING DEVICE (TABLET PRESS CHAMBER CONSTRUCTION)—SINGLE-PUNCH TABLET PRESS (FIG. 1)

[0036] In the vacuum chamber 7 formed by a housing comprising a top wall A1, a bottom wall A2 and side walls A3, there is a tableting mechanism including the tablet press table 2. The tableting mechanism may be selected from a single-punch tablet press or a rotary tablet press. The chamber 7 may be of any construction. It is important, however, that there is enough space for the tableting mechanism and that it is possible to maintain constant pressure in it during the tableting process of the tablet mass. The schematic drawing (FIG. 1) shows a cube-shaped chamber 7, in the upper wall A1 of which the die 5 of a single-punch tablet press tableting mechanism is placed. The tableting mechanism comprises a drive motor 6, eccentrically connected to a movable upper punch 1, die 5 of a tablet press which includes a tablet press cavity 4. Below the cavity 4 there is a fixed lower punch 11, which is seated on the table 2. The tableting mass is fed into the die chamber 4 from a movable hopper 8. And a vacuum pump is connected to the chamber 7 through valve 9 to create a reduced pressure in the chamber 7.

[0037] Another possibility is to place the single-punch tablet press as described above in an additional outer chamber 13, which is also connected to a vacuum pump, not shown in FIG. 2, for clarity, by means of a connection valve 12 located on one of the side walls. The chamber 13 comprises, like the chamber 7, a top wall B1, a bottom wall B2 and side walls B3.

EXAMPLE 3 TABLETING DEVICE (TABLET PRESS CHAMBER CONSTRUCTION)—A ROTARY TABLET PRESS, FIG. 3

[0038] The tableting mechanism, which is a rotary tablet press, is housed in the vacuum chamber 13, in which a reduced pressure/vacuum is produced by means of a vacuum pump, not shown in FIG. 3, for clarity, and connected via valve 12. Wherein, in chamber 13 there is only the tablet press mechanism and drive unit—the tablet press motor 6 is placed outside it. The connecting method of motor 6 with the tablet press mechanism in order to ensure the tightness of the vacuum chamber 13 will be obvious to a person skilled in the field of mechanics.

EXAMPLE 4 TABLETS COMPRESSED IN A SINGLE-PUNCH TABLET PRESS—REDUCED PRESSURE GENERATED IN THE TABLET PRESS CHAMBER (FIG. 1)

[0039] The compression of the tablets was performed under reduced pressure conditions in the tablet press chamber of a single-punch type. For this purpose, a vacuum pump was connected to the sealed lower chamber covering the elements regulating the lower punch and the elements fixing the table and the fixed die. The output pressure on the pump was set in various ranges (0-0.15 MPa). Tableting under standard conditions (atmospheric pressure) was considered a control test.

[0040] a) Microcrystalline cellulose was used as a model substance for the first test. The die 5 and punches 1 and 11, matched to it, were used to carry out the tests. The weight of the tablet substance in the die was 1 g.

[0041] As a result of the tests, the following results were obtained:

TABLE-US-00001 TABLE 1 The results of tests with microcrystalline cellulose Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 6.57 A positive result tablet does (atmospheric not disintegrate pressure) 0.005 MPa 5.84 A positive result tablet does not disintegrate 0.01 MPa 5.61 A positive result tablet does not disintegrate 0.05 MPa 5.19 A positive result tablet does not disintegrate 0.1 MPa 5.04 A positive result tablet does not disintegrate 0.15 MPa 4.87 A positive result tablet does not disintegrate

[0042] The result of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0043] b) For the second test, diatomaceous earth (silica of natural origin—SiO.sub.2) was used as a model substance. Weight of the tableting substance in the die was 1 g. The die 5 and punches 1 and 11, matched to it, were used to carry out the tests. The obtained results are presented in Table 2.

TABLE-US-00002 TABLE 2 The results of tests with diatomaceous earth Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 8.54 A negative result The tablet is capped or disintegrates 0.01 MPa 7.56 A positive result tablet does not disintegrate 0.05 MPa 6.93 A positive result tablet does not disintegrate 0.1 MPa 6.32 A positive result tablet does not disintegrate 0.15 MPa 5.94 A positive result tablet does not disintegrate

[0044] As a result of the experiment, tablets were obtained from a substance that cannot be compressed under atmospheric pressure.

[0045] Another positive effect of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet, the effects of which confirm the observations from the first test with the first model substance (microcrystalline cellulose). The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0046] c) For the third test, diosmin was used as a test substance. The weight of the tablet substance in die 5 was 1 g. The obtained results are shown in Table 3.

TABLE-US-00003 TABLE 3 The results of tests with diosmin Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 7.62 A negative result The tablet is capped or disintegrates 0.01 MPa 7.16 A positive result tablet does not disintegrate 0.05 MPa 6.57 A positive result tablet does not disintegrate 0.1 MPa 6.21 A positive result tablet does not disintegrate 0.15 MPa 5.98 A positive result tablet does not disintegrate

[0047] As a result of the experiment, tablets were obtained from a substance that cannot be subjected to a tableting process under atmospheric pressure.

[0048] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0049] d) For the fourth test, microcrystalline cellulose was used as a model substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. As a result of the tests, the following results were obtained:

TABLE-US-00004 TABLE 4 The results of tests with microcrystalline cellulose Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 3.85 A positive result tablet does (atmospheric not disintegrate pressure) 0.005 MPa 3.32 A positive result tablet does not disintegrate 0.01 MPa 3.01 A positive result tablet does not disintegrate 0.05 MPa 2.86 A positive result tablet does not disintegrate 0.1 MPa 2.52 A positive result tablet does not disintegrate 0.15 MPa 2.45 A positive result tablet does not disintegrate

[0050] The result of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0051] f) For the fifth test, diatomaceous earth (silica of natural origin—SiO.sub.2) was used as a model substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. The obtained results are shown in Table 5.

TABLE-US-00005 TABLE 5 The results of tests with diatomaceous earth Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 3.82 A negative result The tablet is capped or disintegrates 0.01 MPa 3.64 A positive result tablet does not disintegrate 0.05 MPa 3.53 A positive result tablet does not disintegrate 0.1 MPa 3.41 A positive result tablet does not disintegrate 0.15 MPa 3.29 A positive result tablet does not disintegrate

[0052] As a result of the experiment, tablets were obtained from a substance that cannot be compressed under atmospheric pressure.

[0053] Another positive effect of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet, the effect of which confirm the observations from the first test with the first model substance (microcrystalline cellulose). The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0054] g) For the sixth test, micronized diosmin was used as a test substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. The obtained results are shown in Table 6.

TABLE-US-00006 TABLE 6 The results of tests with micronized diosmin Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 3.82 A negative result The tablet is capped or disintegrates 0.01 MPa 3.64 A positive result tablet does not disintegrate 0.05 MPa 3.53 A positive result tablet does not disintegrate 0.1 MPa 3.41 A positive result tablet does not disintegrate 0.15 MPa 3.29 A positive result tablet does not disintegrate

[0055] As a result of the experiment, tablets were obtained from a substance that cannot be subjected to a tableting process under atmospheric pressure.

[0056] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0057] h) For the seventh test, vitamin D3 precoated with hydroxyapatite in a weight ratio of 1:87 plus excipients was used as a test substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. The obtained results are shown in Table 7.

TABLE-US-00007 TABLE 7 The results of tests with vitamin D3 precoated with hydroxyapatite in a weight ratio of 1:87 plus excipients Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 8.11 A negative result The tablet is capped or disintegrates 0.01 MPa 8.02 A positive result tablet does not disintegrate 0.05 MPa 7.91 A positive result tablet does not disintegrate 0.1 MPa 7.76 A positive result tablet does not disintegrate 0.15 MPa 7.45 A positive result tablet does not disintegrate

[0058] As a result of the experiment, tablets were obtained from a mixture that cannot be subjected to a tableting process under atmospheric pressure.

[0059] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

EXAMPLE 5 TABLETS COMPRESSED ON A SINGLE-PUNCH TABLET PRESS—REDUCED PRESSURE GENERATED AROUND THE TABLE PRESS OF A SINGLE-PUNCH TYPE, FIG. 2

[0060] For this purpose, the entire device was placed in a sealed chamber to which a vacuum pump was connected. The output pressure on the pump was set in various ranges (0-0.15 MPa). Tableting under standard conditions (atmospheric pressure) was considered a control test.

[0061] a) For the first test, microcrystalline cellulose was used as a model substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. The weight of the tableting substance in the die was 1 g. As a result of the tests, the following results were obtained:

TABLE-US-00008 TABLE 8 The results of tests with microcrystalline cellulose Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 6.61 A positive result tablet does (atmospheric not disintegrate pressure) 0.005 MPa 5.79 A positive result tablet does not disintegrate 0.01 MPa 5.63 A positive result tablet does not disintegrate 0.05 MPa 5.12 A positive result tablet does not disintegrate 0.1 MPa 4.91 A positive result tablet does not disintegrate 0.15 MPa 4.85 A positive result tablet does not disintegrate

[0062] The result of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0063] b) For the second test, diatomaceous earth (silica of natural origin—SiO2) was used as a model substance. The weight of the tableting substance in the die was 1 g. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. The obtained results are shown in Table 9.

TABLE-US-00009 TABLE 9 The results of tests with diatomaceous earth Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 8.41 A negative result The tablet is capped or disintegrates 0.01 MPa 7.87 A positive result tablet does not disintegrate 0.05 MPa 7.11 A positive result tablet does not disintegrate 0.1 MPa 6.62 A positive result tablet does not disintegrate 0.15 MPa 6.34 A positive result tablet does not disintegrate

[0064] As a result of the experiment, tablets were obtained from a substance that cannot be compressed under atmospheric pressure.

[0065] Another positive effect of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet, the effect of which confirm the observations from the first test with the first model substance (microcrystalline cellulose). The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0066] c) For the third test, diosmin was used as a test substance. The weight of the tableting substance in the die was 1 g. The obtained results are shown in Table 10.

TABLE-US-00010 TABLE 10 The results of tests with diosmin Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 7.74 A negative result The tablet is capped or disintegrates 0.01 MPa 7.17 A positive result tablet does not disintegrate 0.05 MPa 6.69 A positive result tablet does not disintegrate 0.1 MPa 6.18 A positive result tablet does not disintegrate 0.15 MPa 5.95 A positive result tablet does not disintegrate

[0067] As a result of the experiment, tablets were obtained from a substance that cannot be subjected to the tableting process under atmospheric pressure.

[0068] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0069] d) For the fourth test, microcrystalline cellulose was used as a model substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. As a result of the tests, the following results were obtained:

TABLE-US-00011 TABLE 11 The results of tests with microcrystalline cellulose Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 3.83 A positive result tablet does (atmospheric not disintegrate pressure) 0.005 MPa 3.27 A positive result tablet does not disintegrate 0.01 MPa 3.06 A positive result tablet does not disintegrate 0.05 MPa 2.74 A positive result tablet does not disintegrate 0.1 MPa 2.37 A positive result tablet does not disintegrate 0.15 MPa 2.21 A positive result tablet does not disintegrate

[0070] The result of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0071] e) For the fifth test, diatomaceous earth (silica of natural origin—SiO2) was used as a model substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. The obtained results are shown in Table 12.

TABLE-US-00012 TABLE 12 The results of tests with diatomaceous earth Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 3.74 A negative result The tablet is capped or disintegrates 0.01 MPa 3.49 A positive result tablet does not disintegrate 0.05 MPa 3.37 A positive result tablet does not disintegrate 0.1 MPa 3.21 A positive result tablet does not disintegrate 0.15 MPa 3.17 A positive result tablet does not disintegrate

[0072] As a result of the experiment, tablets were obtained from a substance that cannot be compressed under atmospheric pressure.

[0073] Another positive effect of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet, the effects of which confirm the observations from the first test with the first model substance (microcrystalline cellulose). The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0074] g) For the sixth test, micronized diosmin was used as a model substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. The obtained results are shown in Table 13.

TABLE-US-00013 TABLE 13 The results of tests with micronized diosmin Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 3.80 A negative result The tablet is capped or disintegrates 0.01 MPa 3.67 A positive result tablet does not disintegrate 0.05 MPa 3.51 A positive result tablet does not disintegrate 0.1 MPa 3.46 A positive result tablet does not disintegrate 0.15 MPa 3.28 A positive result tablet does not disintegrate

[0075] As a result of the experiment, tablets were obtained from a substance that cannot be subjected to the tableting process under atmospheric pressure.

[0076] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the pressure pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0077] h) For the seventh test, vitamin D3 precoated with hydroxyapatite in a weight ratio of 1:87 plus excipients was used as a test substance. The die 5 and the punches 1 and 11, matched to it, were used to carry out the tests. The obtained results are shown in Table 14.

TABLE-US-00014 TABLE 14 The results of tests with vitamin D3 precoated with hydroxyapatite in a weight ratio of 1:87 plus excipients Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 8.19 A negative result The tablet is capped or disintegrates 0.01 MPa 8.06 A positive result tablet does not disintegrate 0.05 MPa 7.86 A positive result tablet does not disintegrate 0.1 MPa 7.68 A positive result tablet does not disintegrate 0.15 MPa 7.51 A positive result tablet does not disintegrate

[0078] As a result of the experiment, tablets were obtained from a mixture that cannot be subjected to the tableting process under atmospheric pressure.

[0079] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

EXAMPLE 6 TABLETS COMPRESSED IN A ROTARY TABLET PRESS—REDUCED PRESSURE GENERATED AROUND THE TABLET PRESS OF A ROTARY TYPE, FIG. 3

[0080] For this purpose, a vacuum pump was connected to a sealed chamber built around movable parts—die, punches. The output pressure on the pump was set in various ranges (0-015 MPa). Tableting under standard conditions (atmospheric pressure) was considered a control test.

[0081] a) For the first test, microcrystalline cellulose was used as a model substance. The die 15 and the punch 14, matched to it, were used to carry out the tests. The weight of the tableting substance in the die was 1 g. As a result of the tests, the following results were obtained:

TABLE-US-00015 TABLE 15 The results of tests with microcrystalline cellulose Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 6.62 A positive result tablet does (atmospheric not disintegrate pressure) 0.005 MPa 6.12 A positive result tablet does not disintegrate 0.01 MPa 5.71 A positive result tablet does not disintegrate 0.05 MPa 5.14 A positive result tablet does not disintegrate 0.1 MPa 4.96 A positive result tablet does not disintegrate 0.15 MPa 4.82 A positive result tablet does not disintegrate

[0082] The result of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0083] b) For the second test, diatomaceous earth (silica of natural origin—SiO2) was used as a model substance. Weight of the tableting substance in the die was 1 g. The die 15 and the punch 14, matched to it, were used to carry out the tests. The obtained results are shown in Table 16.

TABLE-US-00016 TABLE 16 The results of tests with diatomaceous earth Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 8.61 A negative result The tablet is capped or disintegrates 0.01 MPa 7.74 A positive result tablet does not disintegrate 0.05 MPa 6.87 A positive result tablet does not disintegrate 0.1 MPa 6.29 A positive result tablet does not disintegrate 0.15 MPa 5.97 A positive result tablet does not disintegrate

[0084] As a result of the experiment, tablets were obtained from a substance that cannot be compressed under atmospheric pressure.

[0085] Another positive effect of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet, the effects of which confirm the observations from the first test with the first model (microcrystalline cellulose). The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0086] c) For the third test, diosmin was used as a test substance. The weight of the tablet substance id the die was 1 g. The obtained results are shown in Table 17.

TABLE-US-00017 TABLE 17 The results of tests with diosmin Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 7.63 A negative result The tablet is capped or disintegrates 0.01 MPa 7.18 A positive result tablet does not disintegrate 0.05 MPa 6.49 A positive result tablet does not disintegrate 0.1 MPa 6.24 A positive result tablet does not disintegrate 0.15 MPa 6.01 A positive result tablet does not disintegrate

[0087] As a result of the experiment, tablets were obtained from a substance that cannot be subjected to the tableting process under atmospheric pressure.

[0088] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0089] d) For the fourth test, microcrystalline cellulose was used as a model substance. The die 15 and the punch 14, matched to it, were used to carry out the tests. As a result of the tests, the following results were obtained:

TABLE-US-00018 TABLE 18 The results of tests with microcrystalline cellulose Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 3.91 A positive result tablet does (atmospheric not disintegrate pressure) 0.005 MPa 3.45 A positive result tablet does not disintegrate 0.01 MPa 3.11 A positive result tablet does not disintegrate 0.05 MPa 2.83 A positive result tablet does not disintegrate 0.1 MPa 2.47 A positive result tablet does not disintegrate 0.15 MPa 2.35 A positive result tablet does not disintegrate

[0090] The result of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0091] e) For the fifth test, diatomaceous earth (silica of natural origin—SiO2) was used as a model substance. The die 15 and the punch 14, matched to it, were used to carry out the tests. The obtained results are shown in Table 19.

TABLE-US-00019 TABLE 19 The results of tests with diatomaceous earth Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 3.89 A negative result The tablet is capped or disintegrates 0.01 MPa 3.66 A positive result tablet does not disintegrate 0.05 MPa 3.51 A positive result tablet does not disintegrate 0.1 MPa 3.38 A positive result tablet does not disintegrate 0.15 MPa 3.27 A positive result tablet does not disintegrate

[0092] As a result of the experiment, tablets were obtained from a substance that cannot be compressed under atmospheric pressure.

[0093] Another positive effect of the experiment was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet, the effects of which confirm the observations from the first test with the first model substance (microcrystalline cellulose). The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0094] f) For the sixth test, micronized diosmin was used as a test substance. The die 15 and the punch 14, matched to it, were used to carry out the tests. The obtained results are shown in Table 20.

TABLE-US-00020 TABLE 20 The results of tests with micronized diosmin Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 3.79 A negative result The tablet is capped or disintegrates 0.01 MPa 3.60 A positive result tablet does not disintegrate 0.05 MPa 3.48 A positive result tablet does not disintegrate 0.1 MPa 3.39 A positive result tablet does not disintegrate 0.15 MPa 3.28 A positive result tablet does not disintegrate

[0095] As a result of the experiment, tablets were obtained from a substance that cannot be subjected to the tableting process under atmospheric pressure.

[0096] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

[0097] g) For the seventh test, vitamin D3 precoated with hydroxyapatite in a weight ration of 1:87 plus excipients was used as a test substance. The obtained results are shown in Table 21.

TABLE-US-00021 TABLE 21 The results of tests with vitamin D3 precoated with hydroxyapatite in a weight ration of 1:87 plus excipients Outlet pressure Average thickness on the vacuum of the obtained pump manometer tablet [mm] Observations 0 MPa 0 A negative result The (atmospheric tableting substance does not pressure) form a compact product, the tablet disintegrates when ejected from the die 0.005 MPa 8.14 A negative result The tablet is capped or disintegrates 0.01 MPa 8.10 A positive result tablet does not disintegrate 0.05 MPa 7.89 A positive result tablet does not disintegrate 0.1 MPa 7.64 A positive result tablet does not disintegrate 0.15 MPa 7.21 A positive result tablet does not disintegrate

[0098] As a result of the experiment, tablets were obtained from a mixture that cannot be subjected to the tableting process under atmospheric pressure.

[0099] An additional positive effect of the experiment, as in the first two cases, was the observation of the relationship between the value of the output pressure observed on the vacuum pump manometer and the thickness of the obtained tablet. The higher the starting pressure, the smaller the measured average thickness of the end product observed.

REFERENCE LIST

[0100] 1. Upper punch, [0101] 2. Table, [0102] 3. Vacuum pump outlet opening, [0103] 4. Die chamber, [0104] 5. Die, [0105] 6. Motor, [0106] 7. Sealed chamber with reduced pressure, [0107] 8. Hopper, [0108] 9. Vacuum pump chamber connection valve, [0109] 10. Eccentic, [0110] 11. Lower punch, [0111] 12. Connection valve of the vacuum pump chamber of the outer chamber, [0112] 13. External vacuum chamber, [0113] 14. A rotary tablet press upper punch, [0114] 15. A rotary tablet press rotary die, [0115] 16. Rotary tablet press die base, [0116] A1—vacuum chamber upper wall, [0117] A2—vacuum chamber bottom wall, [0118] A3—vacuum chamber side wall, [0119] B1—external vacuum chamber upper wall, [0120] B2—external vacuum chamber bottom wall, [0121] B3—external vacuum chamber side wall.