CN114425879A

CN114425879A - Tablet press for preparing core-spun tablets, core-spun tablets and preparation method thereof

Info

Publication number: CN114425879A
Application number: CN202011168649.6A
Authority: CN
Inventors: 顾宙辉; 施玉芳
Original assignee: Jiangsu Wanbang Biopharmaceutical Group Co ltd; Shanghai Fosun Xingtai Pharma Technology Co ltd
Current assignee: Jiangsu Wanbang Biopharmaceutical Group Co ltd; Shanghai Fosun Xingtai Pharma Technology Co ltd
Priority date: 2020-10-28
Filing date: 2020-10-28
Publication date: 2022-05-03

Abstract

The invention discloses a three-layer tablet machine for preparing core-spun tablets, the core-spun tablets and a preparation method thereof. The upper punch of the three-layer tablet press has the following characteristics: the middle of the surface of the upper punch is provided with a convex structure, and the total area of the convex structure accounts for 10-95% of the total area of the surface of the upper punch; the height of the protruding structure is 0.5-5 mm; the distance between the edge of the convex structure and the edge of the upper punch is not less than 0.8 mm; on the surface of the upper punch, the surface not covered by the raised structures is a horizontal surface. The upper punch surface of the conventional three-layer tablet press is reasonably designed and used for preparing the core-spun tablets. Compared with the core-spun tablet prepared by adopting a core-spun tablet tabletting machine, the core tablet does not need to be pressed in advance, and the process is simple and easy to operate; and the adopted equipment is a conventional three-layer tablet press, so that the equipment is low in cost and wide in application, and is suitable for large-scale industrial production.

Description

Tablet press for preparing core-spun tablets, core-spun tablets and preparation method thereof

Technical Field

The invention relates to a medicinal preparation, in particular to a tablet press for preparing a core-spun tablet, the core-spun tablet and a preparation method thereof.

Background

The core-spun tablet is a special tablet, and aims to design one or more medicines into a core-spun tablet by a preparation means so as to achieve the technical effects of predetermined medicine release, improvement of product stability, increase of medicine curative effect, reduction of medicine toxic and side effects and the like. The preparation method of the core-spun tablet usually adopts a dry pressing coating technology, firstly a tablet core is pressed, then a core-spun tablet pressing machine is adopted to sequentially fill the first layer of material, the tablet core and the second layer of material, and finally the core-spun tablet is pressed.

Chinese patent CN 106822155B discloses a triple compound tablet-in-tablet composed of tenofovir disoproxil fumarate, efavirenz and lamivudine and a preparation method thereof. The tablet comprises a coated tablet core (pre-pressed and coated) of tenofovir disoproxil fumarate, coated granules prepared from efavirenz, lamivudine and auxiliary materials, and a tablet core, wherein the coated granules and the tablet core are pressed into tablets, so that the problem that the degradation and dissolution of the tenofovir disoproxil fumarate are slow due to contact with other two raw material medicines is solved.

Chinese patent CN 104080446B discloses a dry-press coated tablet containing a proton pump inhibitor and acetylsalicylic acid, which comprises an enteric core tablet of acetylsalicylic acid (pre-press coated), and then with granules containing the proton pump inhibitor, press-coated into a tablet-in-tablet to improve the stability of the product and reduce the gastric ulcer caused by acetylsalicylic acid.

Chinese patent CN 103394087 a discloses a time-delayed dosage form of a drug for the treatment of insomnia, which is preferably provided in the form of a dry-press coated tablet comprising a core containing the drug (pre-compressed), a press coating surrounding the core to obtain a formulation of the drug with a pH-independent time-delayed release.

Chinese patent 201010536147.4 discloses a Xinwei stomach-invigorating core-coated tablet and a preparation method thereof, the Xinwei stomach-invigorating core-coated tablet comprises a tablet core coated with a film coat and a coating layer coated outside the tablet core, wherein the tablet core and the coating layer are formed by combining one or more of rhizoma atractylodis, rheum officinale, scutellaria baicalensis, dried orange peel, sodium bicarbonate and other additives, and the tablet core and the coating layer are pressed by a core-coated tablet pressing machine to obtain the core-coated tablet.

Chinese patent application CN201110454196.8 discloses a prescription composition of a compound antituberculous core-spun tablet and a preparation method thereof. The isoniazide and excipient are tabletted in a wet granulation mode, enteric coating is carried out to obtain a tablet core, rifampicin (or rifampicin and ethambutol hydrochloride, or rifampicin, ethambutol hydrochloride and pyrazinamide) is used as an outer layer, the outer layer and the excipient are granulated in a dry method, and then the granules and the isoniazide enteric tablet core are jointly pressed into the compound antituberculous core-covering tablet.

Chinese patent application No. CN201210268700.X discloses a core-coated tablet prepared from fasudil hydrochloride and pharmaceutically acceptable auxiliary materials, wherein the core-coated tablet comprises a medicament-containing tablet core and a blank layer. The preparation method comprises the steps of granulating fasudil hydrochloride and proper auxiliary materials, pressing the mixture into a tablet core, and pressing the tablet core and blank layer particles into a core-spun tablet.

Chinese patent application CN201510054756.9 discloses an esomeprazole magnesium core-spun tablet and a preparation method thereof. The esomeprazole magnesium core-coated tablet comprises a chip and a peripheral layer, wherein the chip contains the esomeprazole magnesium enteric-coated pellet and an acceptable auxiliary material carrier in the medical field, the peripheral layer contains the acceptable auxiliary material carrier in the medical field, and the chip is tightly wrapped by the peripheral layer. The invention provides a solution for reducing the breakage rate of the enteric layer in the process of tabletting the esomeprazole magnesium enteric-coated pellets, thereby improving the release amount of the drug and ensuring the curative effect of the drug. The invention can also realize that the lower dosage of the plasticizer in the enteric coating is used for enteric pellet tabletting, thereby reducing the preparation process difficulty caused by overhigh dosage of the plasticizer and avoiding the adhesion hidden trouble in the pellet coating and storing process.

Chinese patent application CN201710460214.0 discloses a paliperidone core-coated tablet and a preparation method thereof, comprising the following steps: (1) preparation of the sheet core layer: mixing paliperidone with adjuvants, and compressing to form a core layer; (2) preparing a wrapping layer material: mixing paliperidone with auxiliary materials to obtain a wrapping layer material; (3) preparing a core-spun sheet: pre-filling wrapping layer materials, filling the core layer of the sheet, filling the wrapping layer materials, and pressing to form a core-spun sheet; compared with the original product which is coated by adopting acetone as a solvent, the production process avoids the use of organic solvent, increases the stability of the medicine and reduces the toxic and side effects of the medicine.

Chinese patent application CN201410524731.6 discloses a prednisone pulse release tablet and a preparation method thereof. The prednisone pulse release tablet consists of a quick release tablet core and a controlled release coating layer. The optimized coating weight gain rate of the controlled release coating layer relative to the quick release tablet core is 350-390%; the quick-release tablet core consists of a medicine and inner-layer auxiliary materials, the medicine is prednisone and acetate thereof, and the dosage specification of the medicine is 1-5 mg per tablet by the weight of the prednisone; the controlled release coating layer consists of a coating framework material and a pore-forming agent, wherein the coating framework material is a composition of hydroxypropyl methylcellulose and ethyl cellulose, and the pore-forming agent is mannitol.

The preparation method of the core-spun tablets described in the above patent is a conventional dry-pressing coating technology, and has the following 2 characteristics that firstly, the tablet core needs to be pre-pressed, and secondly, the secondary pressing is needed by adopting a core-spun tablet pressing machine. This particular tablet press is provided with, in addition to 2 hoppers, between which a filling system suitable for feeding the cores is also provided. For each tablet, a first hopper is filled with the bottom material, then the filling system provides and positions the core in the center of the die, then a second hopper is filled with the top material over the core, and finally, compression is performed. Although the technology exists for many years, the market products produced by the technology in the current market have the most significant yield, and the most important reason is that the cost of the core-spun tablet press is too high (the price of the core-spun tablet press for general foreign laboratories is as high as more than 400-500 ten thousand yuan/table), the research and development investment is large, the production process is complicated, and the production efficiency is low, so that the technology is difficult to popularize and apply in actual production.

Disclosure of Invention

The invention aims to overcome the defects that in the prior art, when a dry-pressing coating technology is generally adopted to prepare a core-spun tablet, a core-spun tablet tabletting machine is too high in cost, large in research and development investment, complex in production process, low in production efficiency and difficult to popularize in actual production, and provides a three-layer tablet tabletting machine for preparing the core-spun tablet, the core-spun tablet and a preparation method thereof.

Prior art three-layer tablet presses are typically used to produce tablet products of a conventional three-layer construction, with the edges of the middle layer exposed rather than the core tablet. At present, no precedent exists in the prior art for preparing the core-spun tablets by adopting a conventional three-layer tablet press. In the preparation method, a special tablet press is not needed, only a conventional three-layer tablet press in the field is adopted, the surface of the punch die is designed into a proper convex shape according to the actual requirement, a tablet core is not needed to be pressed in advance, and the core-spun tablet can be directly pressed.

The invention solves the technical problems through the following technical scheme.

The invention also provides a three-layer tablet press for preparing the core-spun tablets, and the upper punch adopted by the three-layer tablet press has the following characteristics:

a convex structure is arranged in the middle of the surface of the upper punch, and the total area of the convex structure accounts for 10-95% of the total area of the surface of the upper punch; the height of the protruding structure is 0.5-5 mm; the edge of the convex structure is not less than 0.8mm away from the surface edge of the upper punch;

the surface of the upper punch, which is not covered by the raised structure, is a horizontal surface.

As is known in the art, the three-layer tablet press comprises, in addition to the upper punch, a lower punch, a middle die, etc., and three positions (a first feeding position, a second feeding position, a third feeding position) for feeding and preparing the three-layer tablet. In the present invention, the apparatus is conventional on a conventional three-layer tablet press except that the pressing surface of the upper punch is modified.

In the present invention, the surface of the punch refers to a surface for forming a compressed tablet by punching.

In the present invention, the number of the protruding structures may be one, or may be multiple, preferably one. When the number of the convex structures is 1, the number of the tablet cores to be pressed is only 1. If the number of the convex structures is more than one, the number of the tablet cores formed by compression corresponds to that of the convex structures.

In the invention, the structure of the convex structure can be one or more of various shapes such as circle, ellipse, heart, capsule, drop, rectangle and polygon.

In the present invention, preferably, the total area of the protrusion structures accounts for 35 to 65% of the total area of the surface of the upper punch.

In the present invention, preferably, the height of the protruding structure is 1.5 to 3.5mm, for example, 2.5 mm.

In the present invention, preferably, the edge of the raised structure is not less than 1.5mm from the surface edge of the upper punch.

The invention also provides a preparation method of the core-spun tablet, which is prepared by adopting the three-layer tablet press and comprises the following steps:

s1, filling wrapping materials at a first feeding position of the three-layer tablet press, and forming a first layer by the upper punch pressing; an upper surface of the first sheet layer includes a recessed portion and a horizontal portion;

s2, at a second feeding position, the lower punch jacks up the first sheet layer to enable the horizontal part of the first sheet layer to be flush with the upper surface of a middle die of the three-layer sheet tablet press, tablet core materials are filled into the concave part of the first sheet layer, and the tablet core layer is formed through the upper punch pressing;

and S3, filling the wrapping material at the third feeding position, and performing compression molding through the upper punch.

In S1, based on the difference of the material of the wrapping layer adopted by the core-spun sheet, a person skilled in the art can adjust and control the hardness of the first sheet layer according to common knowledge. For example, the first sheet layer may be a low hardness sheet layer or loose piece, so that the finally formed core-spun piece has good friability and is not easy to separate.

At S1, the upper surface of the first sheet layer includes a concave portion formed by pressing the convex structure of the upper punch surface and a horizontal portion formed by pressing the surface of the upper punch surface not covered by the convex structure.

In S2, the lower punch jacks up the first sheet layer to make the horizontal portion of the first sheet layer flush with the upper surface of the middle mold of the tablet press, so that the core material is only in the concave portion of the first sheet layer, thereby achieving the wrapping.

At S2, the filling amount of the core material is related to the volume of the concave part of the first layer (i.e. the volume of the convex structure on the upper punching surface of the three-layer tablet machine). Specifically, the volume of the concave part of the first tablet layer needs to be designed according to the weight and the bulk density of the tablet core material.

In the actual industrial production, after the prescription of the core-spun tablets is determined, the bulk density and the filling amount of the core-spun tablets are relatively fixed. The volume of the concave part of the upper surface of the first tablet layer (namely the volume of the convex structure on the upper surface of the three-tablet press) is equal to the volume of the tablet core material. Even if the filling amount of the tablet core materials has small difference, the fine adjustment can be carried out by the stirring speed of the charging hopper. Under the condition of consistent tabletting speed, the stirring speed of the hopper is higher, and the filling amount is relatively larger.

In S2, after the tablet core layer is pressed and formed, the upper punch inserts the first tablet layer and the tablet core layer into a middle mold, and the lower punch position is adjusted, so that the first layer and the tablet core layer are not or hardly stressed, which is beneficial to the press forming of the final core-spun tablet.

In S3, based on the difference of the material of the wrapping layer adopted by the core-spun sheet, a person skilled in the art can adjust and control the hardness of the third sheet layer according to common knowledge.

At S3, the undershoot lifts the first sheet layer and core layer into position for subsequent coating material dosing prior to filling the coating material at the third feeding location, as is known in the art.

In the invention, the core-spun sheet comprises a coating layer and a core sheet, and the formula composition of the coating layer and the core sheet is determined according to the actual prescription. For example, the coating material and core material used to prepare the core tablet may be conventional in the art.

In S1 and S3, the wrapping material is made of the same material and can be determined according to the actual prescription of the core-spun sheet. The form of the coating material can be one or more of granules, powder and pellets.

The mass ratio of the wrapping material in the S1 to the wrapping material in the S3 can be 4: 6-6: 4.

In S2, the core material may be determined according to the actual prescription of the core-spun tablet. The form of the core material can be one or more of granules, powder and pellets.

The invention provides a core-spun tablet prepared by the preparation method of the core-spun tablet.

In the present invention, the upper surface of the core-spun sheet includes a concave portion and a horizontal portion;

wherein the total area of the concave parts accounts for 10-95% of the total area of the upper surface of the core-spun sheet; the depth of the concave part is 0.5-5 mm; the edge of the concave part is not less than 0.8mm away from the edge of the upper surface of the core-spun sheet.

Preferably, the total area of the concave parts accounts for 35-65%, for example 35% or 43%, of the total area of the upper surface of the core-spun sheet.

Preferably, the depth of the concave part is preferably 1.5-3.5 mm, such as 2.0mm or 2.5 mm.

Preferably, the edge of the concave part is not less than 1.5mm, such as 1.5mm or 2.0mm, from the edge of the upper surface of the core-spun sheet.

The structure of the concave part can be one or more of various shapes such as a circle, an ellipse, a heart, a capsule, a water drop, a rectangle and a polygon.

The number of the concave parts may be one or more, and preferably one. Correspondingly, the core tablet of the core-spun tablet can be one or more.

On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.

The reagents and starting materials used in the present invention are commercially available.

The positive progress effects of the invention are as follows:

the upper punch surface of the conventional three-layer tablet press is reasonably designed and used for preparing the core-spun tablets. Compared with the core-spun tablet prepared by adopting a core-spun tablet tabletting machine, the core tablet does not need to be pressed in advance, and the process is simple and easy to operate; and the adopted equipment is a conventional three-layer tablet press, the equipment cost is low (the price of the production type three-layer tablet press is only about 160 ten thousand yuan per table), the applicability is wide, and the method is suitable for large-scale industrial production.

The core-coated tablet of the invention has the functions of the conventional core-coated tablet, such as delayed administration, releases the medicine at a specific time after the medicine is taken to achieve the treatment purpose, for example, the core-coated tablet can be taken before sleeping at night, releases the medicine in the next morning, and is more suitable for treating diseases with circadian rhythm characteristics, such as hypertension, angina pectoris and the like. The embodiment of the present invention is illustrated by using a delayed release sustained release tablet of captopril, a drug for treating hypertension and heart failure, but does not represent that the present invention is only applied to the drug and does not represent that the present invention is only applied to a delayed administration system.

Drawings

Fig. 1 is a schematic structural diagram of a core-spun sheet of embodiment 1.

Fig. 2 is a schematic structural diagram of the core-spun sheet of embodiment 2.

Fig. 3 is a release profile of the core-coated tablet of example 1 and the tablet of comparative example 1.

Fig. 4 is a release profile of the core tablets of examples 1 and 2.

Detailed Description

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.

The raw materials used in the following examples are commercially available.

In the following examples, a three-layer tablet press, model GZPL-1060, three-layer tablet press, available from Xinlongli technologies, Inc., Beijing, was used. In each example, the tablet press was identical for all other devices except for the differences in the upper punch configuration.

Comparative example 1 used a tablet press machine model ZP19 available from newtork technologies ltd, beijing.

Example 1

Captopril delayed release sustained release tablet (Specification 12.5mg)

TABLE 1

The preparation method comprises the following steps:

s1, sieving captopril through a 100-mesh sieve, uniformly mixing the captopril with hydroxypropyl methylcellulose K100M and lactose, and adding magnesium stearate (1) to be uniformly mixed;

dry granulating the mixture by a dry granulator for later use to obtain a tablet core material;

s2, uniformly mixing hydroxypropyl methylcellulose K4M, microcrystalline cellulose KG802, colloidal silicon dioxide sieved by a 40-mesh sieve and magnesium stearate (2) to obtain a wrapping material;

s3, loading the materials into a three-layer tablet press, and adopting circular punching tablets with the diameter of 11.5 mm.

In the three-layer tablet press, 1 circular raised structure is arranged in the middle of the surface of an upper punch, and the total area of the raised structures accounts for 43 percent of the total area of the surface of the upper punch; the height of the protruding structure is 2.0 mm; the edge of the raised structure is 2.0mm away from the surface edge of the upper punch; the surface of the upper punch, which is not covered by the raised structure, is a horizontal surface.

155mg of coating material in the first layer; 25mg of the core layer material in the second layer (core layer) and 120mg of the wrapping layer material in the third layer to obtain the captopril delayed release sustained release tablet (10000 tablets). The position of the upper punch can be adjusted according to the amount in the compression molding process. The preparation method comprises the following steps:

s31, filling 155mg of wrapping material at a first feeding position of the three-layer tablet press, and forming a first layer by punching and pressing; the upper surface of the first sheet layer includes a recessed portion and a horizontal portion; the recessed portions are formed by pressing the raised structures of the upper punch surface and the horizontal portions are formed by pressing the surface of the upper punch surface that is not covered by the raised structures.

The first sheet layer can be a low-hardness sheet layer or loose sheet, so that the finally formed core-spun sheet has good friability and is not easy to separate.

S32, at a second feeding position, downwards punching to jack up the first sheet layer to enable the horizontal part of the first sheet layer to be flush with the upper surface of a middle die of a three-layer sheet tablet machine, so that the tablet core material is only in the concave part of the first sheet layer, 25mg of the tablet core material is filled in the concave part of the first sheet layer, and the tablet core layer is formed through upwards punching and pressing;

after the tablet core layer is pressed and formed, the upper punch inserts the first tablet layer and the tablet core layer into the middle mold, and the lower punch position is adjusted, so that the first layer and the tablet core layer are basically not stressed or are slightly stressed, and the final compression forming of the core-spun tablet is facilitated.

And S33, punching the first sheet layer and the core layer to proper positions at the third feeding position, filling 120mg of wrapping material, and pressing and forming by punching.

Wherein the total area of the recessed portions of the upper surface accounts for 43% of the total area of the upper surface. The upper surface is concave, and the distance from the deepest part to the upper surface is 2.0 mm. The edge of the concave part of the surface is 2.0mm away from the edge of the upper surface. The core-spun sheet is shown in figure 1.

Example 2

Captopril delayed release sustained release tablet (specification 25mg)

TABLE 2

The preparation method comprises the following steps:

s1, sieving captopril through a 100-mesh sieve, uniformly mixing the captopril with hydroxypropyl methylcellulose K100M and lactose, and uniformly mixing the captopril with magnesium stearate (1);

s3, filling the materials into a three-layer tablet press, and punching oval-shaped tablets with the diameter of 20 x 10 mm.

In the three-layer tablet press, 2 heart-shaped convex structures are arranged in the middle of the surface of an upper punch, and the total area of the convex structures accounts for 35% of the total area of the surface of the upper punch; the height of the protruding structure is 2.5 mm; the edge of the raised structure is 1.5mm away from the surface edge of the upper punch; the surface of the upper punch, which is not covered by the raised structure, is a horizontal surface.

The first sheet layer was wrapped with 310mg of the layer material; 50mg of the core layer material in the second layer (core layer) and 240mg of the wrapping layer material in the third layer to obtain the captopril delayed release sustained release tablet (10000 tablets). The position of the upper punch can be adjusted according to the amount in the compression molding process. The preparation method comprises the following steps:

s31, filling a wrapping material of 310mg at a first feeding position of a three-layer tablet press, and forming a first layer by punching and pressing; the upper surface of the first sheet layer includes a recessed portion and a horizontal portion; the recessed portions are formed by pressing the raised structures of the upper punch surface and the horizontal portions are formed by pressing the surface of the upper punch surface that is not covered by the raised structures.

S32, at a second feeding position, downwards punching to jack up the first sheet layer to enable the horizontal part of the first sheet layer to be flush with the upper surface of a middle die of a three-layer sheet tablet machine, enabling the tablet core material to be only in the concave part of the first sheet layer, filling 50mg of the tablet core material into the concave part of the first sheet layer, and pressing through an upper punch to form a tablet core layer;

And S33, punching the first sheet layer and the core layer to proper positions at the third feeding position, filling the wrapping material of 240mg, and pressing and forming by punching.

Wherein the total area of the recessed portions of the upper surface accounts for 35% of the total area of the upper surface. The upper surface is concave, and the distance from the deepest part to the upper surface is 2.5 mm. The edge of the concave part of the surface is 1.5mm away from the edge of the upper surface. The core-spun sheet is shown in figure 2.

Comparative example 1

Captopril sustained-release tablet (Standard 12.5mg)

TABLE 3

The preparation method comprises the following steps:

s1, sieving captopril through a 100-mesh sieve, uniformly mixing the captopril with hydroxypropyl methylcellulose K100M and lactose, and uniformly mixing the captopril with magnesium stearate to obtain a mixture;

s2, dry granulating the mixture by using a dry granulator to obtain a mixture before tabletting;

s3, punching the mixture before tabletting into round tablets with the diameter of 5mm to obtain the captopril sustained-release tablets (10000 tablets and conventional tablets with the diameter of 5 mm).

Effect example 1

The release curve of the captopril delayed release sustained release tablets (examples 1 and 2 and comparative example 1) is determined.

Taking the tablets of example 1, example 2 and comparative example 1, the cumulative release amount was measured and calculated by sampling at 1, 2, 4, 6, 9, 12, 16, 20 and 24 hours according to the first method of dissolution test (basket method) of the supplement of the second part of the pharmacopoeia 2015 edition of China, using water as release medium and rotating at 100 rpm, and operating according to the method, and is shown in fig. 3 and fig. 4.

The release result shows that the example 1 has obvious delayed release behavior relative to the comparative example 1, and the release speed of the tablet is delayed for 4-6 hours.

The release results of example 1 and example 2 show that 2 sizes of tablets have similar delayed release behavior.

Claims

1. A three-layer tablet press for preparing core-spun tablets comprises an upper punch, a middle die and a lower punch, and is characterized in that a raised structure is arranged in the middle of the surface of the upper punch, and the total area of the raised structures accounts for 10-95% of the total area of the surface of the upper punch; the height of the protruding structure is 0.5-5 mm; the edge of the convex structure is not less than 0.8mm away from the surface edge of the upper punch;

2. A three-layer tablet press for making core-spun tablets according to claim 1, wherein the structure of the raised structures is one or more of circular, oval, heart-shaped, capsule-shaped, drop-shaped, rectangular and polygonal;

and/or the total area of the raised structures accounts for 35-65% of the total area of the surface of the upper punch.

3. A three-layer tablet press for making core-spun tablets according to claim 2, wherein the total area of the raised structures represents 35% or 43% of the total area of the surface of the upper punch.

4. A three-layer tablet press for making core-spun tablets according to claim 1, wherein the height of the raised structures is 1.5-3.5 mm;

and/or the edge of the raised structure is no less than 1.5mm from the surface edge of the upper punch.

5. A three-layer tablet press for making core-spun tablets according to claim 1, wherein the height of the raised structures is 2.0mm or 2.5 mm;

and/or the edge of the raised formation is 1.5mm or 2.0mm from the surface edge of the upper punch.

6. A method for preparing core-spun tablets by using a three-layer tablet press according to any one of claims 1 to 5, comprising the steps of:

7. The method of claim 6, wherein in S1 and S3, the coating material is in the form of one or more of granules, powder and pellets;

and/or the mass ratio of the wrapping material in S1 to the wrapping material in S3 is 4: 6-6: 4;

and/or, in S2, the form of the core material is one or more of granules, powder and pellets.

8. A core-spun sheet obtained by the method for producing a core-spun sheet according to claim 6 or 7;

the upper surface of the core-spun sheet comprises a concave part and a horizontal part; the total area of the concave parts accounts for 10-95% of the total area of the upper surface of the core-spun sheet; the depth of the concave part is 0.5-5 mm; the edge of the concave part is not less than 0.8mm away from the edge of the upper surface of the core-spun sheet.

9. A core-spun sheet of claim 8, wherein the total area of the recessed portions is 35 to 65% of the total area of the upper surface of the sheet;

and/or the depth of the concave part is 1.5-3.5 mm;

and/or the edge of the concave part is not less than 1.5mm away from the edge of the upper surface of the core-spun sheet.

10. A core-spun sheet of claim 9, wherein the total area of the recessed portions is 35% or 43% of the total area of the upper surface of the sheet;

and/or the depth of the recessed portion is 2.0mm or 2.5 mm;

and/or the edge of the concave part is 1.5mm or 2.0mm away from the edge of the upper surface of the core-spun sheet.