Dry granulation process of bismuth potassium citrate tablets

Abstract

The invention discloses a preparation method of bismuth potassium citrate tablets through dry granulation and tabletting, and belongs to the technical field of pharmaceutical preparations. The preparation method of the bismuth potassium citrate tablet comprises the following steps: uniformly mixing bismuth potassium citrate with a diluent, a disintegrating agent, an adhesive, a lubricant and the like, putting the mixture into a dry type granulator, adjusting the process parameters of the dry type granulator, extruding the mixture into a blank tablet, and carrying out granule finishing and screening, so as to obtain the bismuth potassium citrate tablet. And uniformly mixing the whole granules with additional auxiliary materials, tabletting and coating to obtain the bismuth potassium citrate tablets. Bismuth potassium citrate particles obtained through a dry granulation process are uniform in particle size, good in fluidity and good in compressibility, then the disintegration property and the dissolution rate of the product are improved to a great extent, the amplification effect is low when the process is put into production, the intra-batch and inter-batch difference of the product is small, and the process is stable and good in reproducibility.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a preparation method of bismuth potassium citrate tablets by dry granulation and tableting. Background Art

[0002] Potassium bismuth citrate is a bismuth-containing complex of indefinite composition. It is a drug for treating gastric and duodenal ulcers. It is also used for combined ulcers, multiple ulcers, anastomotic ulcers, erosive gastritis, and chronic superficial gastritis. It can be used in combination with antibiotics to eradicate Helicobacter pylori. Currently, the bismuth-based quadruple therapy (bismuth + acid inhibitor + two antibiotics) is widely used in clinical practice as a first-line treatment. Potassium bismuth citrate is a white powder that is easily soluble in water and very slightly soluble in ethanol. The drug has a unique mode of action. In the acidic environment of the stomach, it can form a diffuse protective layer on the ulcer surface, thereby preventing gastric acid, enzymes and food from invading the ulcer surface. It can also inhibit the activity of pepsin, increase mucus and bicarbonate secretion, and promote the release of epithelial growth factor and prostaglandin E2 (PGE2). PGE2 is an important cell protective factor that can inhibit gastric acid secretion, thereby protecting the gastric mucosa.

[0003] Bismuth potassium citrate preparations were first developed by Gist-Brocadis (now Astellas Pharma Inc.) of the Netherlands, with the trade name De-nol. In July 2015, Astellas announced that it would stop supplying De-nol from December 31, 2015. Currently, the reference preparation announced by NMPA is the bismuth potassium citrate tablets marketed in Spain by Tora Laboratories SL, with the trade name GASTRODENOL and a specification of 120 mg (in terms of Bi2O3).

[0004] The potassium citrate preparations produced in China now usually adopt a wet granulation process. CN114129532A (patent applicant: Livzon Group) discloses a potassium citrate preparation, the preparation method of which is wet granulation, followed by capsule filling or granulation. The inventor of the present application repeated the preparation method disclosed in the patent and found that potassium citrate is very soluble in water, and it will harden and produce a strong ammonia smell after contacting water, which may cause the production process to be irritating, and the wet granulation process is cumbersome, the free bismuth is high, and the safety is poor. There are also related studies using a powder direct tableting process. CN112263553A (patent applicant: Beijing Xinkaiyuan Pharmaceutical Technology Co., Ltd.) discloses a method for preparing potassium citrate tablets and their application, and the preparation method is dry powder direct tableting. The inventor of the present application repeated the preparation method disclosed in the patent and found that the potassium citrate raw material itself has extremely poor fluidity, resulting in poor fluidity of the total mixed material, and a large weight difference in the tablets during the tableting process. Therefore, it is very necessary to provide a method for preparing potassium bismuth citrate tablets that can reduce the irritation of the production process, improve material fluidity, and simultaneously increase product stability. Summary of the invention

[0005] In view of the deficiencies in the above-mentioned prior art, the object of the present invention is to provide a method for preparing potassium bismuth citrate tablets, so that the prepared particles have a more uniform particle size and good material fluidity, and ensure the dissolution uniformity and weight difference of the tablets.

[0006] To solve the above problems, the technical solution adopted by the present invention is as follows:

[0007] In a first aspect, the present invention provides a bismuth potassium citrate tablet. Taking the total mass of the bismuth potassium citrate tablet as 100%, the bismuth potassium citrate tablet comprises the following components in percentage by mass:

[0008] Bismuth Potassium Citrate 40%-70%

[0009] Thinner 10%-60%

[0010] Disintegrant 1%~10%

[0011] Adhesive 1%~10%

[0012] Lubricant 0.1%~5%

[0013] A preferred embodiment is that, based on the total mass of the bismuth potassium citrate tablets as 100%, the bismuth potassium citrate tablets include the following components in percentage by mass:

[0014] Bismuth Potassium Citrate 40%-70%

[0015] Corn starch 10%-60%

[0016] Polacrilin potassium 2%~6%

[0017] Povidone K30 2%~6%

[0018] Polyethylene glycol 6000 0.5%~5%

[0019] Magnesium stearate 0.5%~5%

[0020] Preferably, in any of the above schemes, the diluent includes at least one of corn starch, microcrystalline cellulose, mannitol and lactose.

[0021] Preferably, in any of the above schemes, the disintegrant comprises at least one of polacrilin potassium, sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose.

[0022] Preferably, in any of the above schemes, the adhesive comprises at least one of povidone K30, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and sodium carboxymethyl cellulose.

[0023] Preferably, in any of the above schemes, the lubricant includes at least one of polyethylene glycol 6000, magnesium stearate, sodium stearyl fumarate, talc, and colloidal silicon dioxide.

[0024] In a second aspect, the present invention provides a method for preparing the potassium bismuth citrate tablets according to the first aspect, which is prepared according to the following steps:

[0025] The potassium bismuth citrate is crushed;

[0026] Weigh bismuth potassium citrate, diluent, disintegrant, binder and lubricant according to the prescribed amount;

[0027] Premixing the potassium bismuth citrate with a diluent, a disintegrant, a binder and a lubricant in a mixer to obtain a premixed material;

[0028] The obtained premixed material is put into a dry granulator, and granulated, sized and sieved to obtain sized granules;

[0029] The whole granules and the added lubricant are mixed in a mixer to obtain a mixed material;

[0030] The total mixed material is compressed into tablets using a rotary tablet press to obtain bismuth potassium citrate tablets;

[0031] Preferably, any of the above schemes has the following process parameters for dry granulation: extrusion pressure is 3MPa-12MPa, extrusion into embryonic flakes with a thickness of 0.5mm-2.0mm, crushing into granules through 18-20 mesh whole granulation, selecting granules with a particle size below 100 mesh less than 5%-30%; screening above 100 mesh intercepting 70%-95%.

[0032] Preferably, in any of the above schemes, in the step of using a rotary tablet press to tablet to obtain bismuth potassium citrate tablets, the tablet core hardness is controlled to be 5kg / cm 2 ~12kg / cm 2 .

[0033] Preferably, any of the above schemes further comprises coating the potassium bismuth citrate tablets after the step of tableting using a rotary tablet press, and controlling the weight gain of the coating layer to be 0.5% to 3%.

[0034] The preparation method of the potassium bismuth citrate tablets provided by the present invention is a dry granulation tableting process, which has good process reproducibility and high safety. The prepared potassium bismuth citrate tablets have small weight difference, rapid disintegration, and low free bismuth, and have good similarity compared with a reference preparation. DETAILED DESCRIPTION

[0035] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention clearer, the present invention is described in detail below in conjunction with some embodiments, but the present invention is not limited to the following embodiments. Any method and material similar or equivalent to the described content can be applied to the method of the present invention. The preferred implementation methods and materials described in the text are for demonstration purposes only.

[0036] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially. Unless otherwise defined, all professional and scientific terms used in the text have the same meanings as those familiar to those skilled in the art.

[0037] The present invention is described in detail below with reference to specific embodiments.

[0038] Example 1

[0039] Bismuth potassium citrate tablets, specification: 120 mg / tablet (calculated as Bi2O3), including the following ingredients in percentage by mass:

[0040] Material Name Weight ratio (%) effect Bismuth Potassium Citrate 70 Active ingredients Corn starch 18 Thinner Polacrilin Potassium 3 Disintegrants Povidone K30 6 Adhesives Polyethylene glycol 6000 1.5 Lubricants Magnesium Stearate 1.5 Lubricants

[0041] The preparation process is a dry granulation tableting process, which includes the following steps:

[0042] (1) pulverizing bismuth potassium citrate;

[0043] (2) Weigh bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, polyethylene glycol 6000, and magnesium stearate according to the prescription;

[0044] (3) The bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, and polyethylene glycol 6000 are premixed in a mixer for 10 minutes, and then the premixed materials are put into a dry granulator for dry granulation and granulation. The equipment parameters of the dry granulation are as follows: the extrusion pressure is 12 MPa, the embryo sheets with a thickness of 1.0 mm are extruded, and the sheets are crushed into granules through 18 mesh granulation. The selected particles have a particle size of less than 100 mesh and a particle size of less than 5% to 30%; the particles with a particle size of more than 100 mesh are screened and retained by 70% to 95%.

[0045] (4) The potassium citrate bismuth granules obtained by dry granulation and magnesium stearate are mixed in a mixer for 15 minutes to obtain a mixed material.

[0046] (5) Use a rotary tablet press to compress the total mixed material into tablets, and control the tablet core hardness to 5 kg / cm 2 ~12kg / cm 2 Obtain bismuth potassium citrate tablets.

[0047] Example 2

[0048] Bismuth potassium citrate tablets, specification: 120 mg / tablet (calculated as Bi2O3), including the following ingredients in percentage by mass:

[0049] Material Name Weight ratio (%) effect Bismuth Potassium Citrate 43 Active ingredients Corn starch 48 Thinner Polacrilin Potassium 6 Disintegrants Povidone K30 2 Adhesives Polyethylene glycol 6000 0.5 Lubricants Magnesium Stearate 0.5 Lubricants

[0050] The preparation process is a dry granulation tableting process, which includes the following steps:

[0051] (1) pulverizing bismuth potassium citrate;

[0052] (2) Weigh bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, polyethylene glycol 6000, and magnesium stearate according to the prescription;

[0053] (3) The bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, and polyethylene glycol 6000 are premixed in a mixer for 10 minutes, and then the premixed materials are put into a dry granulator for dry granulation and granulation. The equipment parameters of the dry granulation are as follows: the extrusion pressure is 3 MPa, the embryo sheets with a thickness of 2.0 mm are extruded, and the sheets are crushed into granules through 20 mesh granulation. The selected particles have a particle size of less than 100 mesh and a particle size of less than 5% to 30%; the particles with a particle size of more than 100 mesh are screened and retained by 70% to 95%.

[0054] (4) The potassium citrate bismuth granules obtained by dry granulation and magnesium stearate are mixed in a mixer for 15 minutes to obtain a mixed material.

[0055] (5) Use a rotary tablet press to compress the total mixed material into tablets, and control the tablet core hardness to 5 kg / cm 2 ~12kg / cm 2Obtain bismuth potassium citrate tablets.

[0056] Example 3

[0057] Bismuth potassium citrate tablets, specification: 120 mg / tablet (calculated as Bi2O3), including the following ingredients in percentage by mass:

[0058] Material Name Weight ratio (%) effect Bismuth Potassium Citrate 57 Active ingredients Corn starch 33 Thinner Polacrilin Potassium 4 Disintegrants Povidone K30 4 Adhesives Polyethylene glycol 6000 1 Lubricants Magnesium Stearate 1 Lubricants

[0059] The preparation process is a dry granulation tableting process, which includes the following steps:

[0060] (1) pulverizing bismuth potassium citrate;

[0061] (2) Weigh bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, polyethylene glycol 6000, and magnesium stearate according to the prescription;

[0062] (3) The bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, and polyethylene glycol 6000 are premixed in a mixer for 10 minutes, and then the premixed materials are put into a dry granulator for dry granulation and granulation. The equipment parameters of the dry granulation are as follows: the extrusion pressure is 8 MPa, the embryo sheets with a thickness of 0.5 mm are extruded, and the sheets are crushed into granules through 18 mesh granulation. The selected particles have a particle size of less than 100 mesh and are less than 5% to 30%; the particles with a particle size of more than 100 mesh are screened and retained by 70% to 95%.

[0063] (4) The potassium citrate bismuth granules obtained by dry granulation and magnesium stearate are mixed in a mixer for 15 minutes to obtain a mixed material.

[0064] (5) Use a rotary tablet press to compress the total mixed material into tablets, and control the tablet core hardness to 5 kg / cm 2 ~12kg / cm 2 Obtain bismuth potassium citrate tablets.

[0065] Example 4

[0066] Bismuth potassium citrate tablets, specification: 120 mg / tablet (calculated as Bi2O3), including the following ingredients in percentage by mass:

[0067] Material Name Weight ratio (%) effect Bismuth Potassium Citrate 72 Active ingredients Corn starch 19 Thinner Polacrilin Potassium 2 Disintegrants Povidone K30 3 Adhesives Polyethylene glycol 6000 2 Lubricants Magnesium Stearate 2 Lubricants

[0068] The preparation process is a dry granulation tableting process, which includes the following steps:

[0069] (1) pulverizing bismuth potassium citrate;

[0070] (2) Weigh bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, polyethylene glycol 6000, and magnesium stearate according to the prescription;

[0071] (3) The bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, and polyethylene glycol 6000 are premixed in a mixer for 10 minutes, and then the premixed materials are put into a dry granulator for dry granulation and granulation. The equipment parameters of the dry granulation are as follows: the extrusion pressure is 8 MPa, the embryo sheets with a thickness of 1.5 mm are extruded, and the sheets are crushed into granules through 18 mesh granulation. The selected particles have a particle size of less than 100 mesh and are less than 5% to 30%; the particles with a particle size of more than 100 mesh are screened and retained by 70% to 95%.

[0072] (4) The potassium citrate bismuth granules obtained by dry granulation and magnesium stearate are mixed in a mixer for 15 minutes to obtain a mixed material.

[0073] (5) Use a rotary tablet press to compress the total mixed material into tablets, and control the tablet core hardness to 5 kg / cm 2 ~12kg / cm 2 Obtain bismuth potassium citrate tablets.

[0074] Comparative Example 1

[0075] Bismuth potassium citrate tablets, specification: 120 mg / tablet (calculated as Bi2O3), including the following ingredients in percentage by mass:

[0076] Material Name Weight ratio (%) effect Bismuth Potassium Citrate 70 Active ingredients Corn starch 18 Thinner Polacrilin Potassium 3 Disintegrants Povidone K30 6 Adhesives Polyethylene glycol 6000 1.5 Lubricants Magnesium Stearate 1.5 Lubricants

[0077] The preparation process is a wet granulation tableting process, which includes the following steps:

[0078] (1) Weigh bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, polyethylene glycol 6000, and magnesium stearate according to the prescription;

[0079] (2) premixing the bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, and polyethylene glycol 6000 in a wet granulator for 10 minutes, adding 80% ethanol to the wet granulator to prepare a soft material, and granulating with a 20-mesh sieve to obtain wet granules;

[0080] (3) placing the wet granules in an oven to dry, and after drying, using a 20-mesh screen to size the granules;

[0081] (4) mixing the whole granules obtained in step (3) with the prescribed amount of magnesium stearate in a mixer for 15 minutes to obtain a mixed material;

[0082] (5) Use a rotary tablet press to compress the total mixed material into tablets, and control the tablet core hardness to 5 kg / cm 2 ~12kg / cm 2 Obtain bismuth potassium citrate tablets.

[0083] Comparative Example 2

[0084] Bismuth potassium citrate tablets, specification: 120 mg / tablet (calculated as Bi2O3), including the following ingredients in percentage by mass:

[0085] Material Name Weight ratio (%) effect Bismuth Potassium Citrate 70 Active ingredients Corn starch 18 Thinner Polacrilin Potassium 3 Disintegrants Povidone K30 6 Adhesives Polyethylene glycol 6000 1.5 Lubricants Magnesium Stearate 1.5 Lubricants

[0086] The preparation process is a dry powder direct tableting process, which includes the following steps:

[0087] (1) Weigh bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, polyethylene glycol 6000, and magnesium stearate according to the prescription;

[0088] (2) premixing the bismuth potassium citrate, corn starch, polacrilin potassium, povidone K30, and polyethylene glycol 6000 in a mixer for 10 minutes to obtain a premixed material;

[0089] (3) adding magnesium stearate to the premixed material, and continuing to mix in a mixer for 10 minutes to obtain a total mixed material;

[0090] (4) Use a rotary tablet press to compress the total mixed material into tablets, and control the tablet core hardness to 5 kg / cm 2 ~12kg / cm 2 Obtain bismuth potassium citrate tablets.

[0091] The powder properties, weight difference and friability of the total mixed granules prepared in Examples 1-4, Comparative Example 1 and Comparative Example 2 were investigated. The results are shown in Table 1.

[0092] Table 1 Summary of powder properties of the total mixed granules and weight differences and friability results during tableting

[0093]

[0094]

[0095] By comparing the powder properties of the total mixed granules prepared in Examples 1-4, Comparative Example 1, and Comparative Example 2 and the weight difference in the tableting process, it can be seen that the total mixed granules prepared in Examples 1-4 have good fluidity; the total mixed granules prepared in Comparative Example 1 and Comparative Example 2 have poor fluidity, and the weight difference of the prepared potassium bismuth citrate tablets exceeds the limit and the friability is large.

[0096] Quality Study of Bismuth Potassium Citrate Tablets:

[0097] Preparation of artificial gastric juice medium: take 234 ml of hydrochloric acid, dilute it to 1000 ml with water, mix well to obtain dilute hydrochloric acid; take 16.4 ml of dilute hydrochloric acid, 800 ml of water and 10 g of pepsin, mix well, then dilute it to 1000 ml with water, stir well to obtain artificial gastric juice.

[0098] Reference preparation: Bismuth potassium citrate tablets, marketed in Spain, licensed by Tora Laboratories SL, trade name GASTRODENOL, specification 120 mg (calculated as Bi2O3). The reference preparations described below are all this preparation.

[0099] (1) Determination of disintegration time in artificial gastric fluid medium

[0100] The hanging basket is suspended on the bracket through the stainless steel shaft at the upper end, immersed in a 1000ml beaker, and the position of the hanging basket is adjusted so that when it drops to the lowest point, the screen is 25mm away from the bottom of the beaker. The beaker contains artificial gastric juice at a temperature of 37℃±1℃. The water level is adjusted so that when the hanging basket rises to the highest point, the screen is 15mm below the water surface, and the top of the hanging basket cannot be immersed in the solution. Take 6 samples of potassium bismuth citrate tablets, place them in the glass tubes of the hanging basket respectively, and start the disintegration instrument for inspection.

[0101] Referring to the above method, the disintegration time of the potassium citrate bismuth tablets prepared in Examples 1-4, Comparative Example 1, and Comparative Example 2 and the reference preparation in artificial gastric juice medium were investigated, and the results are shown in Table 2.

[0102] Table 2 Determination results of disintegration time of Examples 1-4, Comparative Example 1, Comparative Example 2 and reference preparation in artificial gastric fluid medium

[0103] name Disintegration time Example 1 3min48s-4min25s Example 2 3min15s-3min42s Example 3 3min37s-4min02s Example 4 3min50s-4min29s Comparative Example 1 8min12s-8min40s Comparative Example 2 7min55s-8min11s Reference preparation 8min07s-8min33s

[0104] As can be seen from the above table, the disintegration time of Examples 1-4 in the artificial gastric juice medium is significantly faster than that of Comparative Example 1, Comparative Example 2, and the reference preparation, indicating that the potassium bismuth citrate tablets prepared in the present invention disintegrate rapidly.

[0105] (2) Determination of free bismuth

[0106] Step (1), take 20 samples of potassium bismuth citrate tablets, grind them into powder, take about 2.0g of the powder, accurately weigh it, put it in a stoppered conical flask, accurately add 200ml of anhydrous ethanol, seal it, shake it thoroughly for 10 minutes, take the supernatant and filter it, accurately measure 100ml of the filtrate, evaporate it on a water bath, cool it, accurately add 10ml of 2% nitric acid solution to dissolve it, filter it with a 0.45μm microporous filter membrane, and take the filtrate as the test solution.

[0107] Step (2), accurately measure an appropriate amount of a single element bismuth standard solution (1000 μg bismuth per 1 ml), dilute it with a 2% nitric acid solution to prepare a series of bismuth standard solutions containing 1 to 10 μg bismuth per 1 ml as control solutions.

[0108] Step (3), measuring the absorbance of the control solution at a wavelength of 223.1 nm by atomic absorption spectrophotometry, plotting a standard curve with absorbance (Y) as the ordinate and concentration (X) as the abscissa, and obtaining a linear regression equation: Y=0.0140X+0.0.107, R=0.9998; measuring the absorbance of the test solution at a wavelength of 223.1 nm by the above-mentioned atomic absorption spectrophotometry, calculating the free bismuth concentration in the test solution according to the standard curve, and then calculating the free bismuth in the bismuth preparation according to the formula.

[0109] The bismuth single element standard solution used in step (2) has the following model: 100 ml / bottle, element symbol: Bi, serial number: KDZ-230428-01, and mass concentration: 1000 μg / ml.

[0110] The free bismuth of the potassium citrate tablets and the reference preparation prepared in Examples 1-4, Comparative Example 1 and Comparative Example 2 was determined according to the above method. The results are shown in Table 3.

[0111] Table 3 Determination results of free bismuth in Examples 1-4, Comparative Example 1, Comparative Example 2, and Reference Preparation

[0112] name Free bismuth / ppm Example 1 9 Example 2 8 Example 3 8 Example 4 10 Comparative Example 1 32 Comparative Example 2 28 Reference preparation 11

[0113] Calculation formula:

[0114]

[0115] Wherein, C is the concentration of the test solution, μg / ml; 10 is the volume of the test solution, ml; 2 is the multiple; M is the sample weight of the test sample, g.

[0116] It can be seen from the table data that the free bismuth of the potassium citrate tablets prepared in Examples 1-4 is low, which is not much different from the reference preparation, while the free bismuth of the potassium citrate tablets prepared in Comparative Examples 1 and 2 is higher than that of the reference preparation and has poor safety.

[0117] (3) Determination of colloid viscosity

[0118] Step (1), take 2 pieces of potassium bismuth citrate tablets, place them in a beaker, add 200 ml of artificial gastric juice, stir to completely dissolve them, let them stand in a 37°C water bath for 2 hours to allow them to separate, then transfer them to a separatory funnel and let them stand for 10 minutes. After they are separated, separate the colloidal solution at the lower layer.

[0119] Step (2) refers to the third rotational viscometer method of Part IV General Chapter 0633 of the 2020 edition of the Chinese Pharmacopoeia, using rotor No. 61 and a rotation speed of 200 rpm / min to measure the viscosity of the colloidal solution.

[0120] The viscosity of the colloidal solutions formed by Examples 1-4, Comparative Example 1, Comparative Example 2, and the reference preparation in artificial gastric juice medium was measured according to the above method. The measurement results are shown in Table 4.

[0121] Table 4 Viscosity measurement results of colloidal solutions formed by Examples 1-4, Comparative Example 1, Comparative Example 2 and reference preparations in artificial gastric juice medium

[0122] name Viscosity / mPa·s Example 1 4.95 Example 2 5.70 Example 3 4.77 Example 4 5.30 Comparative Example 1 2.15 Comparative Example 2 4.21 Reference preparation 4.71

[0123] As can be seen from the above table, the viscosity of the colloidal solution formed by the potassium citrate bismuth tablets prepared in Examples 1-4 in the artificial gastric juice medium is greater than that of the reference preparation. Viscosity reflects the colloidal properties of the drug. The greater the viscosity, the stronger the protective effect on the ulcer surface. Therefore, the potassium citrate bismuth tablets prepared in the present invention have better therapeutic effects.

[0124] The above are only preferred embodiments of the present invention, and the present invention is not limited thereto. Any non-substantial changes or improvements made on the basis of the present invention should be included in the protection scope of the present invention.

Claims

1. A bismuth potassium citrate tablet, characterized in that: The tablet is composed of potassium citrate bismuth and auxiliary materials, wherein potassium citrate bismuth accounts for 40% to 70% of the tablet core weight. The selected auxiliary materials include any two or more combinations of diluents, disintegrants, adhesives and lubricants.

2. A bismuth potassium citrate tablet according to claim 1, characterized in that: The diluent is selected from at least one of corn starch, pregelatinized starch, mannitol, lactose, microcrystalline cellulose and calcium hydrogen phosphate, accounting for 10% to 60% of the weight of the tablet core.

3. A bismuth potassium citrate tablet according to claim 1, characterized in that: The disintegrant is selected from at least one of polacrilin potassium, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, and cross-linked polyvinylpyrrolidone, accounting for 1% to 10% of the weight of the tablet core.

4. A bismuth potassium citrate tablet according to claim 1, characterized in that: The binder is selected from at least one of hydroxypropyl cellulose, hydroxypropyl methyl cellulose, povidone and sodium carboxymethyl cellulose, accounting for 1% to 10% of the weight of the tablet core.

5. A bismuth potassium citrate tablet according to claim 1, characterized in that: The lubricant is selected from at least one of magnesium stearate, sodium stearyl fumarate, polyethylene glycol, talcum powder and colloidal silicon dioxide, accounting for 0.5% to 5% of the weight of the tablet core.

6. The method for preparing a bismuth potassium citrate tablet according to claim 1, characterized in that: The preparation of the potassium bismuth citrate tablets adopts a dry granulation process, comprising the following steps: (1) pulverizing bismuth potassium citrate; (2) Weigh bismuth potassium citrate, diluent, disintegrant, binder and lubricant according to the prescribed amount; (3) premixing the potassium bismuth citrate with a diluent, a disintegrant, a binder and a lubricant in a mixer to obtain a premixed material; (4) putting the obtained premixed material into a dry granulator, and obtaining granulated particles after granulation, granulation and screening; (5) mixing the whole granules and the added lubricant in a mixer to obtain a mixed material; (6) Using a rotary tablet press, the total mixed material is tableted to obtain bismuth potassium citrate tablets.

7. The method for preparing the bismuth potassium citrate tablet according to claim 6, characterized in that: The particle size of the pulverized potassium bismuth citrate in step (1) is less than 75 μm.

8. The method for preparing the bismuth potassium citrate tablet according to claim 6, characterized in that: The working pressure in step (4) is 3MPa-12MPa, and the embryo sheets with a thickness of 0.5mm-2.0mm are extruded, and the sheets are crushed into granules through 18-mesh or 20-mesh whole grains, and the amount of particles below 100 mesh is controlled to be 5%-30%; the retention amount of particles above 100 mesh is 70%-95%.

9. The method for preparing the bismuth potassium citrate tablet according to claim 6, characterized in that: During the tableting process in step (6), the tablet hardness is controlled to be 5 kg / cm 2 ~12kg / cm 2 10. The method for preparing the bismuth potassium citrate tablet according to claim 6, characterized in that: After the step of tableting using a rotary tablet press, the method further comprises coating the potassium bismuth citrate tablets, and controlling the weight gain of the coating layer to be 0.5% to 3%.

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