CN216536177U

CN216536177U - Sustained-release tablet

Info

Publication number: CN216536177U
Application number: CN202121691343.9U
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: 2021-07-22
Filing date: 2021-07-22
Publication date: 2022-05-17
Anticipated expiration: 2031-07-22

Abstract

The utility model discloses a sustained release tablet. The sustained release tablet comprises a tablet core and a water-insoluble film; the tablet core comprises a quick-release layer of the medicine and a blocking layer which covers the single side or double sides of the quick-release layer of the medicine; the water-insoluble film surrounds the core; and the surface of the water-insoluble film wrapping the retardation layer is provided with drug release holes, and the drug release holes penetrate through the water-insoluble film and are communicated with the retardation layer. The sustained-release tablet has a simple structure, is suitable for a simple preparation process, does not need a core-spun tablet tabletting machine, and can be prepared into a tablet with a delayed release effect only by using a conventional tabletting machine, a coating machine and a laser drilling machine.

Description

Sustained-release tablet

Technical Field

The utility model relates to a sustained-release tablet.

Background

The sustained-release tablet can control the release speed and time of the drug in vivo by a proper way. More and more drugs are required to be prepared into sustained-release tablets. For example, prednisone is a corticoid drug, and is mainly used for treating adult rheumatoid arthritis, diminishing inflammation, relieving pain and relieving symptoms. The chemical name of the compound is 17 alpha, 21-dihydroxypregna-1, 4-diene-3, 11, 20-trione. Molecular formula C₂₁H₂₆O₅Molecular weight of 358.43, structural formula:

rheumatoid arthritis is an autoimmune disease with circadian rhythmicity, and joint stiffness caused by it is most severe in the early morning due to an increase in the levels of proinflammatory cytokines such as IL-6 and tumor necrosis factor alpha (TNF-a) at 2-4 am. Based on this, the foreign horizons pharmaceutical company developed a prednisone sustained release tablet (trade name Rayos) which consists of a drug core and an inactive shell, was administered before bedtime, released prednisone midnight (delayed by about 4 hours), and optimized the drug effect during the early morning disease exacerbation period, thereby reducing the symptoms of early morning joint stiffness and the like without affecting compliance and benefiting patients.

Rayos is a core-spun tablet, a dry-pressing coating technology is adopted in the preparation method, a medicine-containing quick-release tablet core is firstly pressed, then an inactive shell is pressed outside the quick-release tablet core by a core-spun tablet pressing machine, the inactive shell is not disintegrated at first in the gastrointestinal tract, the medicine is not released, under the conditions of digestive juice erosion and capillary action, the physical strength of the inactive shell is reduced, meanwhile, the quick-release tablet core absorbs water to expand, after about 4 hours, the inactive shell is disintegrated, and the inner quick-release tablet core immediately releases the medicine, so that the effect of delaying the release of the medicine is achieved. However, Rayos is prepared by adopting a press coating technology, a tablet press special for pressing core-spun tablets is required for production, but due to the high price, large research and development investment and few applicable products, research and development companies are generally reluctant to specially purchase expensive equipment for two varieties, and the technology is difficult to popularize and apply in actual production.

Chinese patent application CN201410524731.6 discloses a prednisone pulse release tablet and a preparation method thereof. It consists of a quick release tablet core and a controlled release coating layer. The weight gain rate of the controlled release coating layer relative to the optimized coating of the quick release tablet core is 350-390%. The quick-release tablet core consists of a medicament and inner-layer auxiliary materials, the medicament is prednisone and acetate thereof, and the dosage specification of the medicament is 1-5mg per tablet by 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 also adopts dry press coating technology.

Chinese patent application CN201310610389.7 discloses an oral prednisone time-selecting release preparation and a preparation method thereof. The composition consists of 0.3-5 parts of prednisone and derivatives thereof, 10-50 parts of glyceryl behenate and 3-30 parts of hydroxypropyl cellulose; in addition, the composition can also contain a disintegrant and other pharmaceutically acceptable auxiliary materials. The patent discloses a preparation method of tablets and granules, wherein the preparation method of the tablets comprises the steps of firstly preparing a medicament-containing tablet core by a tablet press, then coating by a coating pan, and attaching a delayed coating film to the medicament-containing tablet core so as to obtain the oral prednisone time-selective release tablet. According to examples 7 to 9, the coating weight is larger than that of the tablet core, which results in very long coating process time, extremely low production efficiency and unsuitability for industrial scale-up, and simultaneously, the appearance of the tablet loses edges and corners due to the large coating weight increment, thus affecting the beauty.

Therefore, it is an urgent need to provide a sustained release tablet with simple preparation process and capable of achieving delayed release effect.

SUMMERY OF THE UTILITY MODEL

The utility model aims to overcome the defects that an expensive core-spun tablet tabletting machine is needed for preparing sustained-release tablets, the coating amount is large, the process efficiency is low and the like in the prior art, and provides the sustained-release tablet which is simple in structure, can be prepared by using a simple process without expensive special equipment and has an excellent delayed release effect.

The utility model provides a sustained-release tablet, which comprises a tablet core and a water-insoluble film; the tablet core comprises a quick-release layer of the medicine and a blocking layer which covers the single side or double sides of the quick-release layer of the medicine; the water-insoluble film surrounds the core; and the surface of the water-insoluble film wrapping the retardation layer is provided with drug release holes, and the drug release holes penetrate through the water-insoluble film and are communicated with the retardation layer.

In the present invention, the drug release hole allows gastrointestinal fluids of the human body to contact the retardation layer therethrough. The area of the drug release hole is based on the area of the retardant layer contacting the gastrointestinal fluid of the human body, so that the retardant layer can release according to the required delayed release effect, preferably 25-90%, more preferably 35-70%, such as 39% or 56% of the area of the retardant layer communicated with the drug release hole. The number of the medicine releasing holes can be one or more, preferably one, so that the process is simpler. The diameter of the drug release hole is preferably 5-6 mm.

In the utility model, the tablet core comprises a quick-release drug layer and a single-sided or double-sided blocking layer covering the quick-release drug layer, and the water-insoluble film wraps the tablet core; and a drug release hole is arranged on the surface of the water-insoluble film wrapping the retardation layer, and the drug release hole penetrates through the water-insoluble film and is communicated with the retardation layer.

In the utility model, the tablet core comprises a quick-release drug layer and a retarding layer covering one side of the quick-release drug layer, and the water-insoluble film wraps the tablet core; 2 drug release holes are formed in the surface, wrapped by the water-insoluble film, of the retardation layer, and the drug release holes penetrate through the water-insoluble film and are communicated with the retardation layer.

In the utility model, the tablet core comprises a quick-release drug layer and a retarding layer covering one side of the quick-release drug layer, and the water-insoluble film wraps the tablet core; 3 drug releasing holes are formed in the surface, wrapped by the water-insoluble film, of the retardation layer, and penetrate through the water-insoluble film to reach the retardation layer.

In the utility model, the tablet core comprises a quick-release drug layer and a double-sided blocking layer covering the quick-release drug layer, and the water-insoluble film wraps the tablet core; the surface of the water-insoluble film wrapping the retardation layer is provided with 2 drug release holes (the 2 drug release holes are respectively positioned on the symmetrical surface of the water-insoluble film), and the drug release holes penetrate through the water-insoluble film and are communicated with the retardation layer.

In the utility model, the quick-release layer of the medicine can quickly release the medicine after the retardation layer is disintegrated. The quick-release layer comprises a medicament and an auxiliary material of the quick-release layer.

The medicament can be prepared into various types of sustained-release tablets, and is generally a medicament with the characteristic of circadian rhythm of the treated diseases, such as prednisone, nifedipine, verapamil or nitrendipine. In the present invention, the amount of the drug is selected in a therapeutically effective amount thereof.

The auxiliary materials of the quick release layer can be various auxiliary materials which are conventionally used for the quick release layer in the field, generally comprise a filling agent, a bonding agent, a disintegrating agent and a lubricating agent, and can also comprise other auxiliary materials such as a coloring agent and/or a flavoring agent and the like according to the needs. The specific types of the above-mentioned various immediate release layer excipients can be selected according to the routine in the field. For example, the filler may be one or more of starch (e.g., corn starch), pregelatinized starch, lactose, dextrin, microcrystalline cellulose, mannitol, and dibasic calcium phosphate dihydrate; the binder can be one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, povidone, polyethylene glycol, sucrose, glucose and fructose; the disintegrant can be one or more of carboxymethyl starch sodium, croscarmellose sodium, low substituted hydroxypropyl cellulose and crospovidone; the lubricant may be one or more of magnesium stearate, talc and stearic acid; the colorant may be red iron oxide. The above-mentioned various adjuvants for the immediate release layer can be selected according to their conventional dosage in the field.

In a preferred embodiment of the present invention, the immediate release layer comprises prednisone, a filler, a binder, a disintegrant, and a lubricant, specifically comprises 0.8-6% prednisone, 60-80% filler, 1-10% binder, 10-30% disintegrant, and 0.5-5% lubricant, preferably comprises prednisone, lactose, povidone, croscarmellose sodium, and magnesium stearate, more preferably comprises 0.8-6% prednisone, 60-80% lactose, 1-10% povidone K30, 10-30% croscarmellose sodium, and 0.5-5% magnesium stearate; wherein the percentage is the mass percentage of each component in the quick release layer of the medicine.

In the present invention, the retardation layer may control the delayed release effect, and preferably, the retardation layer may control the delayed release effect not affected by pH, which may include a water-non-swelling matrix material. The amount of the retarding layer is selected to achieve the desired controlled release effect. Preferably, the drug is prednisone, and the content of the retarding layer is 30-80% of the mass of the sustained release tablet, more preferably 45-65%, such as 53%, 48% or 46%.

Wherein, the water-insoluble swelling framework material can be water-insoluble swelling framework material which is conventional in the field, and is preferably selected from one or more of glyceryl behenate, glyceryl monostearate, cetyl alcohol, stearyl alcohol and carnauba wax, and is more preferably glyceryl behenate. The content of the water-non-swellable matrix material may be selected according to the usual content of water-non-swellable matrix material in the art, preferably 30-50%, such as 42% or 48% of the mass of the retardation layer.

The retardation layer may further include various other auxiliary materials conventionally used in retardation layers in the art, such as fillers, binders, and lubricants, as needed.

In a preferred embodiment of the utility model, the drug is prednisone, and the retarding layer comprises a filler, a binder, a lubricant and a glidant, more specifically comprises 30-50% of the filler, 0.1-1% of the glidant, 1-10% of the binder and 1-10% of the lubricant, preferably comprises calcium hydrogen phosphate dihydrate, colloidal silicon dioxide, povidone and magnesium stearate, more preferably comprises 30-50% of the calcium hydrogen phosphate dihydrate, 0.1-1% of the colloidal silicon dioxide, 1-10% of povidone K30 and 1-10% of the magnesium stearate; wherein the percentage is the mass percentage of each component in the retardation layer.

In the present invention, the water-insoluble film prevents the drug from being released from the surface of the immediate drug release layer which is not covered with the retardation layer. The water-insoluble film includes a water-insoluble film-forming material and a plasticizer. The mass of the water-insoluble film, when not perforated, may be 7-30%, preferably 12-20%, for example 17% or 13% of the mass of the tablet core. Preferably, the water-insoluble film can remain unbroken for at least 4 hours in vivo.

Wherein the water-insoluble film-forming material may be a water-insoluble film-forming material conventional in the art, preferably selected from one or more of cellulose acetate, ethyl cellulose, ewing RL and ewing RS, more preferably cellulose acetate, or ethyl cellulose and cellulose acetate. The content of the water-insoluble film-forming material may be selected as required according to the conventional content of the water-insoluble film-forming material in the art, and is preferably 16 to 18% by mass, for example 17% by mass of the sustained-release tablet.

Wherein the plasticizer can be a plasticizer conventional in the art, and can be triethyl citrate and/or diethyl phthalate. The plasticizer content may be selected as is conventional in the art, and is preferably from 5 to 30%, preferably from 8 to 20%, for example 11% or 14% by weight of the water-insoluble film-forming mass.

In a preferred embodiment of the utility model, the drug is prednisone, and the water-insoluble film comprises 16-18% of water-insoluble film-forming material and 5-30% of plasticizer; the water-insoluble film-forming material is preferably cellulose acetate, or ethyl cellulose and cellulose acetate; the plasticizer is preferably triethyl citrate and/or diethyl phthalate; wherein the percentage is the mass percentage of each component in the water-insoluble film-forming material.

In the present invention, the shape of the sustained-release agent may be a shape conventional to those of sustained-release tablets in the art, such as a circle or a special shape (ellipse, capsule, hexagonal, butterfly, etc.).

The utility model also provides a preparation method of the sustained release tablet, which comprises the following steps: tabletting according to the structure of the tablet core and the materials to prepare the tablet core, and coating to ensure that the water-insoluble film coats the tablet core; and (3) punching medicine releasing holes on the surface of the water-insoluble film wrapping the retardant layer, and enabling the medicine releasing holes to penetrate through the water-insoluble film to reach the retardant layer.

Wherein the tableting may be performed in a manner and under conditions conventional in the art. The tabletting can be completed by adopting conventional equipment, a double-layer tablet tabletting machine can be adopted to prepare the tablet core of which the retardation layer covers one side of the quick-release layer of the medicament, and a three-layer tablet tabletting machine can also be adopted to prepare the tablet core of which the retardation layer covers two sides of the quick-release layer of the medicament.

Wherein the coating may be performed in a manner and under conditions conventional in the art. The coating can be accomplished using conventional equipment, such as a coating machine.

Wherein, the punching can be carried out according to the conventional mode and conditions in the field, and a laser punching machine can be adopted for punching.

The above preferred conditions may be combined arbitrarily to obtain preferred embodiments of the present invention without departing from the general knowledge in the art.

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

The positive progress effects of the utility model are as follows: the sustained-release tablet has a simple structure, is suitable for a simple preparation process, does not need a core-spun tablet tabletting machine, and can be prepared into a tablet with a delayed release effect only by using a conventional tabletting machine, a coating machine and a laser drilling machine.

Drawings

FIG. 1 is a cross-sectional view of a single-hole, double-layered disc-shaped tablet of example 4.

Figure 2 is a top view of a single-well, double-layered wafer tablet of example 4.

Fig. 3 is a cross-sectional view of a dual-well, dual-layer disc-like tablet of example 5.

Fig. 4 is a top view of the dual-well, dual-layer disc tablet of example 5.

Fig. 5 is a cross-sectional view of a three-hole, double-layered wafer-shaped tablet of example 6.

Fig. 6 is a top view of a three-hole, double-layered wafer-shaped tablet of example 6.

Figure 7 is a cross-sectional view of a two-well, three-layer disk tablet of example 7.

Figure 8 is a top view of the two-well, three-layer disc tablet of example 7.

FIG. 9 is a graph showing the effect of delayed release measured in effect example 1.

Description of reference numerals:

water-insoluble film: 1

The quick-release layer of the medicine: 2

A retardation layer: 3

Drug release holes: 4.

Detailed Description

The utility model is further illustrated by the following examples, which are not intended to limit the scope of the utility model. 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.

Example 1

Prednisone sustained-release tablets (specification 5mg)

TABLE 1

The preparation method comprises the following steps:

s1, weighing a quick release layer material of a tablet medicament; dissolving polyvidone K30 in purified water to obtain binder; mixing prednisone, lactose, croscarmellose sodium and iron oxide red in a wet granulator, wet granulating with povidone K30 water solution, wet granulating with a conical granulator, fluidized bed drying, dry granulating with a conical granulator, and mixing with magnesium stearate to obtain prednisone medicine layer granule;

s2, weighing materials of a retardation layer; uniformly mixing calcium hydrogen phosphate dihydrate, polyvidone K30 and glyceryl behenate (888ATO) in a wet granulator, wet granulating with purified water as wetting agent, wet granulating with a conical granulator, drying with a fluidized bed, dry granulating with the conical granulator, and mixing with colloidal silicon dioxide and magnesium stearate to obtain retardant layer granule;

s3, filling the materials into a double-layer tablet press, and pressing the double-layer tablet core by using a circular punch with the diameter of 8 mm. The first layer is a prednisone-containing medicine quick-release layer, and the second layer is a retardation layer;

s4, weighing a water-insoluble membrane material; dissolving cellulose acetate and diethyl phthalate in acetone and isopropanol to obtain coating solution; putting the double-layer tablet core into a coating pan, preheating, controlling the air outlet temperature within a proper range, and spraying coating liquid to obtain a coated tablet;

s5, drilling a hole on one side of the white surface (a blocking layer and a drug quick-release layer which are red) of the double-layer tablet by adopting a laser drilling machine to obtain the prednisone sustained-release tablet (10000 tablets) with the hole diameter of 6 mm.

Example 2

Prednisone sustained-release tablets (Specification 1mg)

TABLE 2

The preparation method comprises the following steps:

s1, weighing a quick-release layer of a medicine; dissolving polyvidone K30 in purified water to obtain binder; mixing prednisone, lactose, croscarmellose sodium and iron oxide red in a wet granulator, wet granulating with povidone K30 water solution, wet granulating with a conical granulator, fluidized bed drying, dry granulating with a conical granulator, and mixing with magnesium stearate to obtain prednisone medicine layer granule;

s2, weighing materials of a retardation layer; uniformly mixing calcium hydrogen phosphate dihydrate, polyvidone K30 and octadecanol in a wet granulator, wet granulating with purified water as wetting agent, wet granulating with a conical granulator, fluidized bed drying, dry granulating with the conical granulator, and uniformly mixing with colloidal silicon dioxide and magnesium stearate to obtain retardant layer granules for later use;

s3, filling the materials into a double-layer tablet press, and pressing the double-layer tablet core by using a circular punch with the diameter of 8 mm. The first layer is a prednisone-containing medicine layer, and the second layer is a retarding layer;

s4, weighing a water-insoluble membrane material; dissolving ethyl cellulose, cellulose acetate and triethyl citrate in acetone and isopropanol to obtain coating solution; putting the double-layer tablet core into a coating pan, preheating, controlling the air outlet temperature within a proper range, and spraying coating liquid to obtain a coated tablet;

s5, drilling a hole on one side of the white surface (a blocking layer and a drug quick-release layer which are red) of the coated double-layer tablet by adopting a laser drilling machine, wherein the hole diameter is 5mm, and thus obtaining the prednisone sustained-release tablet (10000 tablets).

Example 3

Prednisone sustained-release tablets (Specification 2mg)

TABLE 3

The preparation method comprises the following steps:

s4, weighing a water-insoluble membrane material; dissolving cellulose acetate and triethyl citrate in acetone and isopropanol to obtain coating solution; putting the double-layer tablet core into a coating pan, preheating, controlling the air outlet temperature within a proper range, and spraying coating liquid to obtain a coated tablet;

s5, perforating one side of the white surface of the double-layer tablet (a blocking layer and a drug quick-release layer are red) by the coated tablet by adopting a laser perforating machine, and obtaining the prednisone slow-release tablet (10000 tablets) with the aperture of 6 mm.

EXAMPLE 4 Single-well, double-layer tablet

Fig. 1 shows a cross-sectional view of a sustained-release tablet, which includes: a water-insoluble membrane 1, a drug quick-release layer 2, a retardation layer 3 and a drug release hole 4; the quick-release layer 2 and the retardation layer 3 are adhered together by a tabletting, the quick-release layer 2 and the retardation layer 3 are wrapped by the water-insoluble film 1, and the drug release holes 4 penetrate through the water-insoluble film 1 and lead to the retardation layer 3.

Fig. 2 shows a top view of a sustained release tablet comprising: a water-insoluble membrane 1 and drug release holes 4.

EXAMPLE 5 double-well, double-layer tablet

Fig. 3 shows a cross-sectional view of a sustained-release tablet, which includes: a water-insoluble membrane 1, a drug quick-release layer 2, a retardation layer 3 and a drug release hole 4; the quick-release layer 2 and the retardation layer 3 are adhered together by a tabletting, the quick-release layer 2 and the retardation layer 3 are wrapped by the water-insoluble film 1, and the drug release holes 4 penetrate through the water-insoluble film 1 and lead to the retardation layer 3.

Fig. 4 shows a top view of a sustained release tablet comprising: a water-insoluble membrane 1 and drug release holes 4.

EXAMPLE 6 three-hole, double-layer tablet

Fig. 5 shows a cross-sectional view of a sustained-release tablet, which includes: a water-insoluble membrane 1, a drug quick-release layer 2, a retardation layer 3 and a drug release hole 4; the quick-release layer 2 and the retardation layer 3 are adhered together by a tabletting, the quick-release layer 2 and the retardation layer 3 are wrapped by the water-insoluble film 1, and the drug release holes 4 penetrate through the water-insoluble film 1 and lead to the retardation layer 3.

Fig. 6 shows a top view of a sustained release tablet comprising: a water-insoluble membrane 1 and drug release holes 4.

EXAMPLE 7 double-well, triple-layer tablet

Fig. 7 shows a cross-sectional view of a sustained-release tablet, which includes: a water-insoluble membrane 1, a drug quick-release layer 2, a retardation layer 3 and a drug release hole 4; the quick-release layer 2 and the retardation layer 3 are adhered together by a tabletting, the quick-release layer 2 and the retardation layer 3 are wrapped by the water-insoluble film 1, and the drug release holes 4 penetrate through the water-insoluble film 1 and lead to the retardation layer 3.

Fig. 8 shows a top view of a sustained release tablet comprising: a water-insoluble membrane 1 and drug release holes 4.

Comparative example 1

A commercially available prednisone sustained release tablet (trade name Rayos, specification 5mg) which is a core-coated tablet and is prepared by adopting a dry press coating technology.

Effect example 1

The release curve of the prednisone sustained-release tablets (example 1 and comparative example 1) of the present invention is measured as shown in fig. 9 and table 4.

Taking the tablets of example 1 and comparative example 1, according to the second method of dissolution determination (paddle method) in the appendix of the second part of the Chinese pharmacopoeia 2020 edition, using water as release medium and a rotation speed of 100 revolutions per minute, the cumulative release was determined and calculated by sampling at 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10 hours operating according to the method.

The release results show that example 1 has the same delayed release behavior relative to comparative example 1, and the release rate of the tablet is delayed by about 4 hours.

TABLE 4

Claims

1. A sustained-release tablet, which is characterized by comprising a tablet core and a water-insoluble film; the tablet core comprises a quick-release layer of the medicine and a blocking layer which covers the single side or double sides of the quick-release layer of the medicine; the water-insoluble film surrounds the core; and the surface of the water-insoluble film wrapping the retardation layer is provided with drug release holes, and the drug release holes penetrate through the water-insoluble film and are communicated with the retardation layer.

2. The sustained-release tablet of claim 1, wherein the area of the drug release holes is 25 to 90% of the area of the retardation layer to which the drug release holes are communicated.

3. The sustained-release tablet of claim 2, wherein the area of the drug release holes is 35 to 70% of the area of the retardation layer to which the drug release holes are communicated.

4. The sustained-release tablet of claim 3, wherein the area of the drug release holes is 39% or 56% of the area of the retardation layer to which the drug release holes are communicated.

5. The sustained-release tablet of claim 1, wherein the number of the drug release holes is one or more.

6. The sustained-release tablet of claim 5, wherein the number of the drug release holes is one.

7. The sustained-release tablet of claim 1, wherein the release holes have a hole diameter of 5 to 6 mm.

8. The sustained-release tablet of any one of claims 1 to 7, wherein the tablet core comprises a drug immediate-release layer and a single-sided or double-sided blocking layer covering the drug immediate-release layer, and the water-insoluble film wraps the tablet core; and a drug release hole is arranged on the surface of the water-insoluble film wrapping the retardation layer, and the drug release hole penetrates through the water-insoluble film and is communicated with the retardation layer.

9. The sustained-release tablet of any one of claims 1 to 7, wherein the core comprises a drug immediate-release layer and a single-sided retarding layer covering the drug immediate-release layer, and the water-insoluble film covers the core; 2 drug release holes are formed in the surface, wrapped by the water-insoluble film, of the retardation layer, and the drug release holes penetrate through the water-insoluble film and are communicated with the retardation layer.

10. The sustained-release tablet of any one of claims 1 to 7, wherein the core comprises a drug immediate-release layer and a single-sided retarding layer covering the drug immediate-release layer, and the water-insoluble film covers the core; 3 drug releasing holes are formed in the surface, wrapped by the water-insoluble film, of the retardation layer, and penetrate through the water-insoluble film to reach the retardation layer.

11. The sustained-release tablet of any one of claims 1 to 7, wherein the tablet core comprises a drug immediate-release layer and a double-sided blocking layer covering the drug immediate-release layer, and the water-insoluble film wraps the tablet core; 2 drug release holes are formed in the surface, wrapped by the water-insoluble film, of the retardation layer, and the drug release holes penetrate through the water-insoluble film and are communicated with the retardation layer.

12. The sustained-release tablet of claim 11, wherein the core comprises an immediate-release layer of the drug and a double-sided retarding layer covering the immediate-release layer of the drug, and the water-insoluble film covers the core; 2 drug release holes are formed in the surface, wrapped by the water-insoluble film, of the retardation layer, the 2 drug release holes are respectively located on the symmetrical surface of the water-insoluble film, and the drug release holes penetrate through the water-insoluble film and are communicated with the retardation layer.