Tongbianning tablets, Tongbianning film-coated tablets and preparation methods thereof

Abstract

The invention discloses a Tongbianning tablet, a Tongbianning film-coated tablet and a preparation method thereof. The preparation method of the Tongbianning tablet comprises: granulating a prescribed amount of white cardamom powder, amomum powder, morning glory seed powder and senna leaf dry paste powder with purified water as a binder to obtain primary granules; granulating with a sucrose solution as a binder to obtain sugar-coated granules; adding silicon dioxide and cross-linked sodium carboxymethyl cellulose, mixing and tableting to obtain Tongbianning tablets. The Tongbianning tablets produced by the preparation method can significantly improve friability, increase hardness, make the mechanical strength of the tablet core meet the requirements of film coating, and significantly shorten the disintegration time limit, thereby improving bioavailability; after coating, the moisture-proof performance is good, the stability of the drug is increased, the product quality is guaranteed, and there is a broad market prospect.

Description

Technical Field

[0001] The present invention belongs to the field of Chinese patent medicine preparations, and more specifically, relates to a Tongbianning tablet, a Tongbianning film-coated tablet and a preparation method thereof. Background Art

[0002] Tongbianning Tablets are included in the eleventh volume of the "Standards for the Conversion of New Drugs to Drug Standards of the Ministry of Health of the People's Republic of China". In 1993, it was approved by the Ministry of Health as a third-category new Chinese medicine. The current implementation standard is the National Drug Standard WS3-03(Z-02)-96(Z)-2017 of the State Food and Drug Administration. It is composed of senna leaves, morning glory seeds, amomum villosum, and white cardamom. It has the effects of relieving stomach discomfort and regulating qi, and purging and relieving constipation. It is suitable for constipation caused by excess heat. The preparation process is: 320g of senna leaf dry powder, 133.4g of morning glory seeds, 13.3g of amomum villosum, and 13.3g of cardamom. For the above four ingredients, take morning glory seeds, amomum villosum, and cardamom, grind them into fine powder, mix them with senna leaf dry powder, granulate them, add an appropriate amount of magnesium stearate, and press them into 1000 tablets. According to many years of production practice, there are certain drawbacks in the production process of Tongbianning Tablets, such as:

[0003] (1) The disintegration time of Tongbianning tablets produced using the legal standard process often fails to meet the standard. The disintegration time is greater than the 60 minutes specified in the Chinese Pharmacopoeia. The failure to meet the standard disintegration time affects the quality and efficacy of the product.

[0004] (2) Tongbianning tablets are plain tablets with strong hygroscopicity. After being put on the market, the tablets are prone to absorbing moisture and turning black, as well as sticking together, posing certain risks to product quality.

[0005] Film coating refers to coating the surface of the drug tablet core with a relatively stable polymer coating. Since the film coating is much thinner than the sugar-coated tablet coating, it is also called film coating. Film-coated tablets have become the development direction of tablet drugs and are recognized by patients. However, the brittleness and core hardness of the Tongbianning tablets produced by the statutory standard process do not meet the mechanical strength requirements of the film-coated tablet core. The coating process has serious problems of loose tablets and disintegration of tablets and cannot be smoothly film-coated. The applicant's project team studied a new preparation method for Tongbianning tablets, which can shorten the disintegration time of Tongbianning tablets to about 40 minutes. However, after the core prepared by the new preparation method was directly film-coated, it failed to be film-coated smoothly, and the problem of Tongbianning tablets absorbing moisture and turning black and sticking could not be solved, and its disintegration time limit was greater than 60 minutes specified in the "Chinese Pharmacopoeia".

[0006] So far, there is no Tongbianning film-coated tablet product on the market. Summary of the invention

[0007] Based on this, the object of the present invention is to provide a Tongbianning tablet, a Tongbianning film-coated tablet and a preparation method thereof.

[0008] The technical solutions for achieving the above-mentioned invention objectives include the following.

[0009] The first aspect of the present invention provides a method for preparing a Tongbianning tablet, comprising the following steps:

[0010] (1) Granulate the prescribed amount of white cardamom powder, amomum villosum powder, morning glory seed powder and senna leaf dry extract powder with purified water as a binder to obtain primary granules;

[0011] (2) Granulating with a sucrose solution containing 5% to 10% of the mass of the initial granules as a binder to obtain sugar-coated granules; the sucrose solution is prepared according to a ratio of sucrose to boiling water of 1:4 to 1:6;

[0012] (3) Add silicon dioxide and cross-linked sodium carboxymethyl cellulose to the sugar-coated granules, mix and compress the mixture into tablets to obtain Tongbianning tablets; the amount of silicon dioxide used is 0.5% to 2% of the mass of the sugar-coated granules; the amount of cross-linked sodium carboxymethyl cellulose used is 3% to 5% of the mass of the sugar-coated granules.

[0013] The second aspect of the present invention provides Tongbianning tablets prepared by the above preparation method.

[0014] The third aspect of the present invention provides a Tongbianning film-coated tablet, which is prepared by using the above-mentioned Tongbianning tablet as the tablet core and spray-coating the outer surface with a water-soluble film coating material; the water-soluble film coating material is a gastric-soluble film coating powder; the mass concentration of the water-soluble film coating material is 12% to 16%; the amount of the water-soluble film coating material is 4% to 5% of the weight of the tablet core.

[0015] In the present invention, qualified primary granules are first subjected to secondary granulation and syrup coating, and then mixed with cross-linked sodium carboxymethyl cellulose and silicon dioxide for tableting. The core of the Tongbianning tablet produced by the preparation method can significantly improve the friability and hardness, so that the mechanical strength of the core meets the requirements of film coating, and the disintegration time is significantly shortened, thereby improving the bioavailability; after coating, the moisture-proof performance is good, the stability of the drug is increased, the product quality is guaranteed, and the market prospect is broad. DETAILED DESCRIPTION

[0016] In order to facilitate the understanding of the present invention, the present invention will be described more fully below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0017] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used in the present invention includes any and all combinations of one or more of the related listed items.

[0018] The experimental methods in the following examples where specific conditions are not specified are generally carried out under conventional conditions, such as those described in Green and Sambrook et al., Molecular Cloning: A Laboratory Manual (2013), or according to the conditions recommended by the manufacturer. The various commonly used chemical reagents used in the examples are all commercially available products.

[0019] The preparation method of the Tongbianning tablets of the present invention is prepared by the following steps: firstly, white cardamom powder, amomum powder, morning glory seed powder and senna leaf dry paste powder are mixed, and granules are prepared in one step to obtain primary granules; the primary granules are secondary granulated with 5% to 10% sucrose syrup to obtain sugar-coated granules; the sugar-coated granules are uniformly mixed with 3% to 5% of cross-linked carboxymethyl cellulose sodium and 0.5% to 2% of silicon dioxide, and then tabletted to obtain the Tongbianning tablets. The Tongbianning tablets prepared by the preparation method of the present invention have a sucrose adhesive solution that increases the surface tension and negative pressure suction between particles, and the silicon dioxide can adsorb the oily and insoluble components in the seed of the morning glory raw material. Therefore, the hardness of the tablet core is greatly improved, the brittleness is significantly improved, and the mechanical strength of the tablet core can meet the requirements of film coating (the Tongbianning tablets are spray-coated with a water-soluble film coating material to obtain the Tongbianning film-coated tablets); and because a layer of sucrose coating is evenly coated on the surface of the qualified primary particles, the sucrose coating layer is combined with the cross-linked carboxymethyl cellulose and silicon dioxide added later. A dissolution layer channel is formed. After the dissolution layer channel contacts water, sucrose dissolves rapidly, the volume of the cross-linked carboxymethyl cellulose expands rapidly, and the particles quickly disperse, thereby significantly shortening the disintegration time (the disintegration time of the Tongbianning tablets produced by the legal standard process is often more than 60 minutes, and the disintegration time of the Tongbianning film-coated tablets produced by the preparation method of the present invention is shortened to 38-45 minutes, which meets the requirement of the Chinese Pharmacopoeia of "complete disintegration within 1 hour"), improving bioavailability, and at the same time, the moisture-proof performance after coating is good, which increases the stability of the drug and ensures product quality.

[0020] In some embodiments of the present invention, a method for preparing a Tongbianning tablet is disclosed, comprising the following steps:

[0021] (1) Granulate the prescribed amount of white cardamom powder, amomum villosum powder, morning glory seed powder and senna leaf dry extract powder with purified water as a binder to obtain primary granules;

[0022] (2) Granulating with a sucrose solution containing 5% to 10% of the mass of the initial granules as a binder to obtain sugar-coated granules; the sucrose solution is prepared according to a ratio of sucrose to boiling water of 1:4 to 1:6;

[0023] (3) Add silicon dioxide and cross-linked sodium carboxymethyl cellulose to the sugar-coated granules, mix and compress the mixture to obtain tablet cores; the amount of silicon dioxide is 0.5% to 2% of the mass of the sugar-coated granules; the amount of cross-linked sodium carboxymethyl cellulose is 3% to 5% of the mass of the sugar-coated granules.

[0024] In some embodiments, the amount of the sucrose solution in step (2) is 8% to 10% of the mass of the primary particles.

[0025] In some of the embodiments, the amount of silicon dioxide used in step (3) is 1% to 2% of the mass of the sugar-coated granules.

[0026] In some of the embodiments, the amount of cross-linked sodium carboxymethyl cellulose used in step (3) is 4% to 5% of the mass of the sugar-coated granules.

[0027] In some of the embodiments, during the granulation process in step (1) and step (2), the material temperature is controlled at 40-75° C., and after the binder is sprayed, the material is dried to a moisture content of 2%-4%.

[0028] In some embodiments, during the granulation process of step (1), sampling is taken to check that the particle size of the particles is 16-60 mesh and the percentage is more than 90%, and the spraying of purified water is stopped.

[0029] In some embodiments, step (2) further comprises the step of dividing the sugar-coated granules into two parts, 40-60 mesh and 16-40 mesh.

[0030] In some of the embodiments, in step (3), the silicon dioxide is first mixed with the 40-60 mesh sugar-coated particles, and then the 16-40 mesh sugar-coated particles and the cross-linked sodium carboxymethyl cellulose are added.

[0031] In other embodiments of the present invention, the Tongbianning tablets prepared by the above preparation method are disclosed.

[0032] In other embodiments of the present invention, a Tongbianning film-coated tablet is disclosed, which is prepared by using the above-mentioned Tongbianning tablet as the tablet core and spray-coating a water-soluble film coating material on the outside; the water-soluble film coating material is a gastric-soluble film coating powder; the mass concentration of the water-soluble film coating material is 12% to 16%; the amount of the water-soluble film coating material is 4% to 5% of the weight of the tablet core.

[0033] The equipment and testing instruments used in the following examples are: ZB-1E intelligent disintegrator, CS-1 friability tester, YD-3 hardness tester, HZD800B automatic lifting hopper mixer, HTD-400 column hopper mixer, FL-200 boiling drying granulator, YK-160A swing granulator, GZPL40C high-speed rotary tablet press. The pressure adjustment in the following examples will be different for different instruments, and the qualified particle size range can be ensured by adjusting the pressure and the amount of water spray.

[0034] The present invention is described in detail below with reference to specific embodiments.

[0035] Example 1

[0036] The preparation method of the Tongbianning tablet provided in this embodiment comprises the following steps:

[0037] (1) Mixing

[0038] Weigh the prescribed amount of white cardamom powder and amomum powder, mix them evenly by hand, pass through a 14-mesh sieve, and place in an HTD-400 column hopper mixer; place the prescribed amount of morning glory seed powder and senna leaf dry paste powder in an HTD-400 column hopper mixer. Mix at a speed of 10 rpm for 30 minutes, and crush with a hammer mill. After the crushed powder is passed through a 14-mesh sieve, place in an HTD-400 column hopper mixer, and mix at a speed of 10 rpm for 30 minutes to obtain a Tongbianning mixed powder.

[0039] (2) Preparing primary particles

[0040] Add Tongbianning mixed powder to FL-200 boiling drying granulator, start FL-200 boiling drying granulator according to the operation process, adjust the appropriate air intake to preheat the material, when the exhaust temperature reaches ≥35℃, spray purified water for granulation, the material temperature in the production process is controlled at 40~75℃, start granulation by spraying water at a low speed, adjust the water spraying speed after the material has granules, take samples to check the particle size of 16~60 mesh particles to more than 90% during the granulation process, stop spraying water, dry until the moisture content of the particles is 2~4%, and get the primary granules. If there is agglomeration during the granulation process, use YK-160A swing granulator (14~16 mesh) to disassemble the granules and re-granulate.

[0041] (3) Sugar-coated granules

[0042] Add the primary granules into the FL-200 boiling drying granulator, start the FL-200 boiling drying granulator according to the operating procedures, adjust the appropriate air intake to preheat the material, and when the exhaust temperature reaches ≥35°C, spray 10% sucrose solution (configured as sucrose: boiling water = 1:4-1:6) into the granules. During the production process, the material temperature is controlled at 40-75°C, and the sucrose solution is sprayed evenly at a low speed until it is sprayed. Dry to 2-4% moisture to obtain sugar-coated granules, which are divided into two parts: 40-60 mesh and 16-40 mesh.

[0043] (4) Mixed tableting

[0044] 2% silicon dioxide is passed through a 40-mesh sieve and added to 40-60-mesh granules. After being fully mixed, the mixture is placed in a HZD800B automatic lifting hopper mixer. 16-40-mesh granules and 5% cross-linked sodium carboxymethyl cellulose are added and mixed for 15 minutes. The mixture is compressed using a GZPL40C high-speed rotary tablet press to obtain Tongbianning tablets.

[0045] The Tongbianning film-coated tablets provided in this embodiment are prepared by using the above-mentioned Tongbianning tablets as the tablet core and spray-coating the water-soluble film coating material on the outside. The specific steps of coating are as follows:

[0046] Use gastric soluble film coating powder excipients (Yicai gastric soluble film coating powder (YCW-C-080587); batch number: 220116; manufacturer: Anhui Shanhe Pharmaceutical Excipients Co., Ltd.), add water to prepare a 12% coating suspension, the dosage is 4% of the weight of the tablet core. Preheat the drum, pour the tablet core to be coated, and preheat the tablet core to about 45-55℃. Adjust the nozzle of the spray gun to make the spray liquid into a suitable atomization state. During the coating process, the speed of the coating cylinder is controlled at 3 to 6 rpm. The outlet air temperature during the coating process should be controlled at 45-73℃, and the inlet air temperature is generally ≤100℃. The main principle is that the outlet air temperature is within the control range. After spraying the prepared film coating suspension, stop the machine, turn off the hot air, turn on the exhaust to slowly reduce the temperature of the coated tablets to room temperature, and you will get the Tongbianning film-coated tablets.

[0047] Example 2

[0048] The preparation method of Tongbianning tablets and Tongbianning film-coated tablets provided in this embodiment has the same specific operation steps as those in Example 1, except that: (3) in the step of preparing sugar-coated granules, 5% sucrose (prepared into a sucrose solution according to the ratio of sucrose to boiling water = 1:4-1:6) is sprayed into the granules.

[0049] Example 3

[0050] The preparation method of Tongbianning tablets and Tongbianning film-coated tablets provided in this embodiment has the same specific operation steps as those in Example 1, except that: (4) in the mixing and tableting step, the amount of silicon dioxide used is 0.5%, and the amount of cross-linked sodium carboxymethyl cellulose used is 5%.

[0051] Example 4

[0052] The preparation method of Tongbianning tablets and Tongbianning film-coated tablets provided in this embodiment has the same specific operation steps as those in Example 1, except that: (4) in the mixing and tableting step, the amount of silicon dioxide used is 2% and the amount of cross-linked sodium carboxymethyl cellulose used is 3%.

[0053] Comparative Example 1

[0054] The preparation method of Tongbianning tablets and Tongbianning film-coated tablets provided in this comparative example has the same specific operation steps as Example 1, except that: (4) in the mixing and tableting step, only 2% silicon dioxide is used, and no cross-linked sodium carboxymethyl cellulose is used.

[0055] Comparative Example 2

[0056] The preparation method of Tongbianning tablets and Tongbianning film-coated tablets provided in this comparative example has the same specific operation steps as Example 1, except that: (4) in the mixing and tableting step, 0.5% magnesium stearate is used, and silicon dioxide and cross-linked sodium carboxymethyl cellulose are not used.

[0057] Comparative Example 3

[0058] The preparation method of Tongbianning tablets and Tongbianning film-coated tablets provided in this comparative example has the same specific operation steps as Example 1, except that: (4) in the mixing and tableting step, 0.5% magnesium stearate and 5% cross-linked sodium carboxymethyl cellulose are used, and silicon dioxide is not used.

[0059] Comparative Example 4

[0060] The specific operation steps of the preparation method of Tongbianning tablets and Tongbianning film-coated tablets provided in this comparative example are basically the same as those of Example 1, except that: the step (3) of preparing sugar-coated granules is not performed.

[0061] Comparative Example 5

[0062] The preparation method of Tongbianning tablets and Tongbianning film-coated tablets provided in this comparative example has the same specific operation steps as Example 1, except that the primary granulation step uses sucrose solution as a binder for one-step granulation, and does not perform the sugar-coated granulation step. The primary granulation step is specifically as follows:

[0063] Add the Tongbianning mixed powder into the FL-200 boiling drying granulator, start the FL-200 boiling drying granulator according to the operating procedures, adjust the appropriate air intake to preheat the material, and when the exhaust temperature reaches ≥35°C, spray 10% sucrose (prepared into a sucrose solution according to sucrose: boiling water = 1:4-1:6) into the Tongbianning mixed powder for one-step granulation. During the production process, the material temperature is controlled at 40-75°C, and the adhesive solution is sprayed evenly at a low speed until it is sprayed. After spraying, take samples to check that the particle size of 16-60 mesh particles reaches more than 90%, and stop granulation; if the particle size of 16-60 mesh particles does not reach more than 90%, continue to granulate with purified water until the particle size of 16-60 mesh particles reaches more than 90%. If there is agglomeration during the granulation process, use a swing granulator (14 mesh) to disassemble the particles and granulate again.

[0064] Comparative Example 6

[0065] This comparative example is to prepare the Tongbianning tablet core according to the legal standard process, and then film-coat the tablet core. The specific operation is as follows:

[0066] (1) Mixed

[0067] Weigh the prescribed amount of white cardamom powder and amomum powder and mix them evenly by hand, then add the morning glory seed powder and mix them evenly by hand, and mix them in an automatic lifting hopper for 10 minutes; then add the prescribed amount of senna leaf dry paste powder and mix them in an automatic lifting hopper for 10 minutes; disperse through a 14-18 mesh sieve to obtain the Tongbianning mixed powder.

[0068] (2) Granulation

[0069] Add the mixed powder to the FL-200 boiling drying granulator, start the FL-200 boiling drying granulator according to the operating procedures, adjust the appropriate air intake to preheat the material, and when the exhaust temperature reaches ≥35℃, spray purified water for granulation. The material temperature during the production process is controlled at 40-75℃. Start granulation by spraying water at a low speed. After the material has granules, increase the water spraying speed. During the granulation process, take samples to check the particle size of 20-60 mesh particles. If the particle size reaches 60%-80%, stop spraying water, dry to 4-5% moisture, and pass through a 12-14 mesh sieve. If there is agglomeration during the granulation process, use a swing granulator (14 mesh) to disassemble the granules and granulate again.

[0070] (3) Mixed tableting

[0071] Place the Tongbianning granules in an automatic lifting hopper mixer, add (85±10)% ethanol and mix evenly, pass through a 14-16 mesh sieve. Place it in an automatic lifting hopper mixer again, add 0.5% magnesium stearate (pass through a 40 mesh sieve), mix for 30 minutes, and press into tablets to obtain the Tongbianning film-coated tablet cores.

[0072] (4) Coating

[0073] Use gastric soluble film coating powder excipients (Yicai gastric soluble film coating powder (YCW-C-080587); batch number: 220116; manufacturer: Anhui Shanhe Pharmaceutical Excipients Co., Ltd.), add water to prepare a 12% coating suspension, the dosage is 4% of the weight of the tablet core. Preheat the drum, pour the tablet core to be coated, and preheat the tablet core to about 45-55°C. Adjust the nozzle of the spray gun to make the spray liquid into a suitable atomization state. During the coating process, the speed of the coating cylinder is controlled at 3-6 rpm. The outlet air temperature during the coating process should be controlled at 45-73°C, and the inlet air temperature is generally ≤100°C. The main principle is that the outlet air temperature is within the control range. After spraying the prepared film coating suspension, stop the machine, turn off the hot air, turn on the exhaust to slowly reduce the temperature of the coated tablets to room temperature, and you will get the Tongbianning film-coated tablets.

[0074] Comparative Example 7

[0075] This comparative example is a preparation method of Tongbianning tablet core according to a new preparation method of Tongbianning tablet (patent publication number CN107335002A), and then film coating the tablet core. The specific operation is as follows:

[0076] (1) First granulation

[0077] The invention relates to a method for preparing the following steps: weighing a prescribed amount of Pharbitidis seed powder, Amomum villosum powder and Cardamom powder, placing the powder in an FL-200 fluidized bed drying granulator, starting the FL-200 fluidized bed drying granulator, adjusting the induced draft pressure to 27 MPa, setting the inlet air temperature to 60° C., circulating the materials for uniform mixing, and mixing for 10 minutes; then adjusting the induced draft pressure to 48 MPa, spraying purified water after the inlet air temperature reaches 75° C., suspending the spraying of purified water when the exhaust air temperature is lower than 38° C., and continuing to spray purified water after the temperature rises; sampling and measuring the particle size range of the obtained particles during the water spraying process, and stopping the water spraying until particles with a particle size between 20 and 60 meshes account for 60% of the total particles.

[0078] (2) Second granulation

[0079] The first granules and the prescribed amount of senna leaf dry powder are placed alternately in a FL-200 fluidized bed drying granulator in batches, the FL-200 fluidized bed drying granulator is started, the induced draft pressure is adjusted to 27 MPa, the inlet air temperature is set to 60° C., the materials are circulated and mixed evenly, and the mixing time is 10 minutes; then the induced draft pressure is adjusted to 48 MPa, and after the inlet air temperature reaches 75° C., purified water is sprayed in, and when the exhaust air temperature is lower than 38° C., the spraying of purified water is stopped, and the spraying of purified water can be continued after the temperature rises; during the water spraying process, samples are taken to determine the particle size range of the obtained particles, and the water spraying is stopped until the particles with a particle size between 20 and 60 meshes account for 60% of the total particles, and the drying is continued for 5 minutes before discharging the material, and the particles are sieved through a 14-mesh sieve to obtain the second granules.

[0080] (3) Tableting

[0081] 0.5% magnesium stearate is added to the granules after granulation, mixed evenly, and pressed into tablets to obtain the core of the Tongbianning tablets.

[0082] (4) Coating

[0083] Use gastric soluble film coating powder excipients (Yicai gastric soluble film coating powder (YCW-C-080587); batch number: 220116; manufacturer: Anhui Shanhe Pharmaceutical Excipients Co., Ltd.), add water to prepare a 12% coating suspension, the dosage is 4% of the weight of the tablet core. Preheat the drum, pour the tablet core to be coated, and preheat the tablet core to about 45-55°C. Adjust the nozzle of the spray gun to make the spray liquid into a suitable atomization state. During the coating process, the speed of the coating cylinder is controlled at 3-6 rpm. The outlet air temperature during the coating process should be controlled at 45-73°C, and the inlet air temperature is generally ≤100°C. The main principle is that the outlet air temperature is within the control range. After spraying the prepared film coating excipient suspension, stop the machine, turn off the hot air, turn on the exhaust to slowly reduce the temperature of the coated tablets to room temperature, and you will get the Tongbianning film-coated tablets.

[0084] Test Example: Determination of Indexes of Tongbianning Film-Coated Tablets

[0085] The hardness (YD-3 hardness tester), friability (CS-1 friability tester), and disintegration time (ZB-1E intelligent disintegrator) of the core of the Tongbianning tablets prepared in Examples 1 to 4 and Comparative Examples 1 to 7 were measured; the coating condition and disintegration time of the Tongbianning film-coated tablets were also measured. The results are shown in Table 1.

[0086] Table 1

[0087]

[0088]

[0089] As can be seen from Table 1, the Tongbianning film-coated tablets (Comparative Example 6) prepared by the statutory standard process (adding 0.5% magnesium stearate tableting after one-step granulation) are coated, and the friability and core hardness of the tablets do not meet the mechanical strength requirements of the film-coated tablets, and the coating process has the problem of cracking and disintegration of the tablets. The film-coated tablets are easy to adhere to the baffle pump, and the disintegration time exceeds 60 minutes. After spraying 5% to 10% sucrose solution on the surface of the primary granules to prepare sugar-coated granules, and then mixed with 0.5% to 2% silicon dioxide and 3% to 5% cross-linked carboxymethyl cellulose for tableting, and then coated with the Tongbianning film-coated tablets (Examples 1 to 4), the disintegration time of the tablet core is significantly shortened, the hardness is greatly improved, the friability is reduced, the film coating process has no cracking and disintegration phenomenon, the color of the tablets is uniform, there are no defects such as pitting and collapse, and the disintegration time of the coated tablets meets the "complete disintegration within 1 hour" stipulated in the Chinese Pharmacopoeia. It is speculated that the disintegration mechanism of the Tongbianning film-coated tablets of the present invention is: a layer of sugar coating is evenly coated on the surface of the qualified primary particles, and the sugar coating layer forms a dissolution layer channel with the cross-linked carboxymethyl cellulose and silicon dioxide that are added later. After the dissolution layer channel contacts water, sucrose dissolves rapidly, the volume of the cross-linked carboxymethyl cellulose expands rapidly, and the particles quickly spread apart, thereby shortening the disintegration time. Among them, the Tongbianning film-coated tablets prepared in Example 1 have the best comprehensive performance.

[0090] Compared with Example 1, the Tongbianning film-coated tablets of Comparative Example 1 did not use cross-linked sodium carboxymethyl cellulose during the tableting process; the hardness of the tablet core was greatly reduced, the friability was slightly reduced, the disintegration time was significantly prolonged, and although there were no defects in the film coating process, the film-coated tablets occasionally adhered to the baffle pump, and the disintegration time exceeded 60 minutes. The Tongbianning film-coated tablets of Comparative Example 2 did not use silicon dioxide and cross-linked sodium carboxymethyl cellulose during the tableting process; the hardness of the tablet core was greatly reduced, the friability was slightly reduced, and the disintegration time was significantly prolonged. Although there were no defects in the film coating process, the disintegration time was significantly prolonged. The Tongbianning film-coated tablets of Comparative Example 3 did not use silicon dioxide during the tableting process; the hardness of the tablet core was greatly reduced, the friability was slightly reduced, and the disintegration time was significantly prolonged. The Tongbianning film-coated tablets of Comparative Example 4 did not undergo the step of preparing sugar-coated granules; the hardness of the tablet core was greatly reduced, the friability was reduced, the disintegration time was significantly prolonged, the film coating process showed the phenomenon of flakes and tablet collapse, the film-coated tablets were easily adhered to the baffle pump, and the disintegration time exceeded 60 minutes. Therefore, in the preparation process of the Tongbianning film-coated tablets, any one of the auxiliary materials of sucrose, cross-linked carboxymethyl cellulose and silicon dioxide was lacking, the tablet core hardness and friability would deteriorate, the disintegration time would increase to varying degrees, the film-coated tablets occasionally adhered to the baffle during the coating process, and the disintegration time exceeded 60 minutes.

[0091] Compared with Example 1, in Comparative Example 5, sucrose solution is used as a binder for one-step granulation, and the step of preparing sugar-coated granules is not performed. The hardness and brittleness of the core of the Tongbianning film-coated tablets of Comparative Example 5 are comparable to the core performance of the Tongbianning film-coated tablets of Example 1. The disintegration time of the core tablets is about 38 minutes for most tablets, but occasionally a piece of sticking to the baffle plate extends the disintegration time to 55 minutes; there is no cracking or disintegration of the tablets during the film coating process, the tablet color is uniform, there are no defects such as pockmarks and broken edges, and occasionally the film-coated tablets stick to the baffle pump, and the disintegration time exceeds 60 minutes. The result shows that the combination of 5% to 10% sucrose, 3% to 5% cross-linked carboxymethyl cellulose and 0.5% to 2% silicon dioxide is positive for shortening the disintegration time of Tongbianning tablets. The reason why Comparative Example 5 has a long disintegration time may be that sucrose is used as a binder for one-step granulation, and the material powder is mutually aggregated into particles through the bridging effect of sucrose solution, so more sucrose is needed to increase the surface tension and negative pressure suction between particles. The amount of 10% sucrose is relatively insufficient, and there is an occasional unqualified disintegration time of the tablet. While Example 1 first uses water as a binder to prepare particles, and the particles increase the surface tension and negative pressure suction between particles by the bridging effect of sucrose solution, and 10% sucrose is enough to greatly improve the hardness and brittleness of the tablet core. Therefore, in the preparation method of the present invention, after granulating with pure water first, the step of "carrying secondary granulation and sugar coating on qualified particles" is added, so that the specific surface area can be reduced, the amount of auxiliary materials required is reduced, and the three auxiliary materials play a role of disintegration in a concentrated manner.

[0092] Comparative Example 7 is a new preparation method for Tongbianning tablets, which can shorten the disintegration time of Tongbianning tablets to about 40 minutes. However, the brittleness and hardness of the tablet cores prepared by the new preparation method do not meet the mechanical strength requirements of the tablet cores for film coating. Flakes and tablet disintegration problems occur during the coating process. After film coating, the disintegration time limit is greater than 60 minutes specified in the "Chinese Pharmacopoeia", and the film coating cannot be successfully performed. Therefore, it is also impossible to solve the problem that Tongbianning tablets are prone to moisture absorption, blackening, and adhesion.

[0093] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0094] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A method for preparing Tongbianning film-coated tablets, characterized in that: The following steps are involved: (1) Granulate the prescribed amount of white cardamom powder, amomum powder, morning glory seed powder and senna leaf dry extract powder with purified water as a binder to obtain primary granules; the water content of the primary granules is 2% to 4%; the prescribed amount is: 320g of senna leaf dry extract powder, 133.4g of morning glory seed, 13.3g of amomum, and 13.3g of cardamom per 1000 tablets of Tongbianning film coating; (2) Granulating with a sucrose solution of 5% to 10% of the mass of the initial granules as a binder to obtain sugar-coated granules, and dividing the sugar-coated granules into 40-60 mesh and 16-40 mesh; the sucrose solution is prepared according to the ratio of sucrose to boiling water = 1:4 to 1:6; the water content of the sugar-coated granules is 2% to 4%; (3) First, silicon dioxide is mixed with 40-60 mesh sugar-coated granules, and then 16-40 mesh sugar-coated granules and cross-linked sodium carboxymethyl cellulose are added, and the mixture is compressed into tablets to obtain tablet cores; the amount of silicon dioxide used is 0.5% to 2% of the mass of the sugar-coated granules; the amount of cross-linked sodium carboxymethyl cellulose used is 3% to 5% of the mass of the sugar-coated granules.

2. The method for preparing the Tongbianning film-coated tablets according to claim 1, characterized in that: The amount of sucrose solution used in step (2) is 8% to 10% of the mass of the primary particles.

3. The method for preparing the Tongbianning film-coated tablets according to claim 1, characterized in that: The amount of silicon dioxide used in step (3) is 1% to 2% of the mass of the sugar-coated granules.

4. The method for preparing the Tongbianning film-coated tablets according to claim 1, characterized in that: The amount of cross-linked sodium carboxymethyl cellulose used in step (3) is 4% to 5% of the mass of the sugar-coated granules.

5. The method for preparing the Tongbianning film-coated tablets according to any one of claims 1 to 4, characterized in that: During the granulation process in step (1) and step (2), the material temperature is controlled at 40-75°C.

6. The method for preparing the Tongbianning film-coated tablets according to any one of claims 1 to 4, characterized in that: During the granulation process of step (1), sampling is performed to check if the particle size of the particles is 16-60 mesh and the particle size is more than 90%, and the spraying of purified water is stopped.

7. The method for preparing the Tongbianning film-coated tablets according to any one of claims 1 to 4, characterized in that: The method further comprises the step of spray coating the tablet core of step (3) with a water-soluble film coating material; the water-soluble film coating material is a gastric-soluble film coating powder; the mass concentration of the water-soluble film coating material is 12% to 16%; and the amount of the water-soluble film coating material is 4% to 5% of the weight of the tablet core.

8. Tongbianning film-coated tablets prepared by the preparation method according to any one of claims 1 to 7.

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