WO2018210177A1

WO2018210177A1 - Rapidly disintegrating oral tablet for treating hyperphosphatemia prepared by 3d printing technology, and preparation method therefor

Info

Publication number: WO2018210177A1
Application number: PCT/CN2018/086323
Authority: WO
Inventors: 卜昕; 王鑫桐; 鲁再丰; 赵伟
Original assignee: 西安棣加生物科技有限公司
Priority date: 2017-05-17
Filing date: 2018-05-10
Publication date: 2018-11-22
Also published as: CN107213126B; CN107213126A

Abstract

Disclosed are a rapidly disintegrating oral tablet for treating hyperphosphatemia prepared by 3D printing technology, and a preparation method therefor. The preparation method involves: thoroughly mixing medical-grade raw material powder lanthanum carbonate and auxiliary materials until uniform, and preparing same into tablets by powder and liquid 3D printing technology and by using a mixed solution of an ethanol aqueous solution, glycerin, polysorbate and copovidone S-630. The amount of drug loaded in the prepared tablet is high, and the tablet disintegrates easily, can improve patient compliance, and is suitable for the precisely dosed treatment of hyperphosphatemia in patients with chronic renal failure.

Description

Oral rapid disintegrating tablet for treating hyperphosphatemia prepared by 3D printing technology and preparation method thereof

Technical field

The invention belongs to the field of medicine, and particularly relates to an oral rapid disintegrating tablet for treating hyperphosphatemia prepared by a 3D printing technology and a preparation method thereof.

Background technique

3D printing originated in the United States at the end of the 19th century, but it did not develop until the 1980s. 3D printing technology was originally applied in the fields of manufacturing, aerospace and industrial design. With the development and maturity of 3D printing technology, this emerging technology has entered the field of medicine, and in the manufacture of medical models, tissue regeneration, and clinical repair treatment. And a series of research results have been achieved in drug development experiments. On July 31, 2015, the US Food and Drug Administration approved Aprecia Pharmaceuticals' first Spritam (Levilatacetam) instant tablet prepared by 3D printing technology for use in combination with other anti-epileptic drugs for adults or A seizure, a myoclonic episode, and a primary generalized seizure in a child patient. This means that 3D printing technology will further advance into the pharmaceutical field after printing human organs.

3D printing technology pharmaceuticals use layer-by-layer powder printing, and the prepared tablets are in a network structure; the method uses an aqueous fluid to combine a multi-layer powder mixture to produce a porous water-soluble matrix, which has a good disintegration effect. To solve the problem of swallowing for the patient. Spritam is made into a porous structure by 3D printing technology, and the powder is bonded without compression, and the proportion of the main powder is improved.

In 2004, the US FDA approved cesium carbonate for the treatment of hyperphosphatemia. Barium carbonate is a new generation of phosphorus and binder containing no aluminum and calcium developed by Shire Pharmaceuticals of the United Kingdom. The marketing of strontium carbonate provides a more effective treatment for patients with advanced kidney disease. At present, the clinical use of strontium carbonate drugs mainly consists of chewable tablets, but it has the disadvantages of poor mouthfeel, difficulty in swallowing, cumbersome production process, and the like, and it is difficult for some patients to take.

Although there have been reports of different 3D printed tablets and commercial products available, there are no reports on the formulation of cesium carbonate 3D printing drugs and printing processes for treating hyperphosphatemia. The development of individualized precise dose therapy of strontium carbonate 3D tablets is currently an urgent problem to be solved.

Summary of the invention

One of the objects of the present invention is to provide a rapid disintegrating tablet for treating hyperphosphatemia prepared by a 3D printing technique, which has the characteristics of large drug loading, high hardness and easy disintegration of the oral cavity; and the second object of the present invention is to provide the object Preparation method of oral rapid disintegrating tablets.

In order to achieve the above object, the present invention adopts the following technical solutions:

A rapid disintegrating tablet for treating hyperphosphatemia prepared by a 3D printing technique, the oral disintegrating tablet comprising a pharmaceutical grade raw powder component and a binder, the pharmaceutical grade raw powder component by mass percentage 30 to 75% of strontium carbonate, 5 to 30% of disintegrant, 2 to 40% of filler, 0 to 20% of diluent, 0 to 25% of sweetener, and 1 to 25% of adhesion a composition of 0.3 to 3% of a lubricant and 0.05 to 2% of a flavoring agent; or the pharmaceutical grade raw powder component comprises the above components in mass percentage; the amount of the binder in the tablet is medicinal 0.01 to 0.1 times the weight of the raw powder component;

The following technical solutions are also available:

A rapid disintegrating tablet for treating hyperphosphatemia prepared by a 3D printing technique, characterized in that the oral disintegrating tablet comprises a pharmaceutical grade raw powder component and a binder, and the pharmaceutical grade raw powder group According to the mass percentage, 25 to 80% of barium carbonate, 1 to 35% of disintegrant, 1 to 40% of filler, 0 to 30% of diluent, 0 to 25% of sweetener, 0.5 to 35% of the binder, 0.1 to 5% of the lubricant and 0.01 to 5% of the flavoring agent; the amount of the binder in the tablet is 0.01 to 1 times the weight of the pharmaceutical grade raw powder component.

Preferably, the disintegrant is selected from the group consisting of microcrystalline cellulose, dry starch or alginic acid; the filler is selected from the group consisting of starch, dextrin, mannitol or sorbitol; the diluent is selected from the group consisting of lactose; The agent is selected from the group consisting of sucrose; the binder is selected from the group consisting of povidone, copovidone, hydroxypropyl cellulose, hydroxypropyl methyl cellulose or ethyl cellulose; the lubricant is selected from magnesium stearate, fine powder Silica gel or talc; the flavoring agent is selected from the group consisting of sucralose or powdered sugar; the binder is selected from the group consisting of aqueous ethanol solution, starch solution or addition of povidone, copovidone, glycerin, polysorbate, hydroxypropyl An aqueous solution of at least one of cellulose and hydroxypropylmethylcellulose; preferably, the aqueous ethanol solution has a volume percentage of ethanol of 5 to 60%.

Preferably, the disintegrant is selected from the group consisting of microcrystalline cellulose, dry starch, alginic acid, protein powder, sodium sea oxalate, low-substituted hydroxypropyl cellulose, crospovidone, calcium carboxymethyl cellulose and/or carboxylate. One or more of sodium cellulose and the like; the filler is selected from one or more of starch, dextrin, mannitol, and/or sorbitol; and the diluent is selected from the group consisting of lactose and calcium hydrogen phosphate. One or more of calcium carbonate and/or calcium sulfate; the sweetener is selected from one or more of sucrose and/or acesulfame; and the binder is selected from the group consisting of povidone One or more of copolyvidone, gelatin, methyl ether cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and/or ethyl cellulose; the lubricant is selected from the group consisting of hard fat One or more of magnesium acid, fine powder silica gel and/or talc powder; the flavoring agent is selected from one or more of sucralose and/or rock sugar powder; and the binder is selected from the group consisting of Sucrose solution, sodium alginate solution, aqueous ethanol solution, aqueous methanol solution, starch solution, aqueous methyl cellulose solution, aqueous sodium carboxymethyl cellulose solution and/or added Povidone, copovidone, glycerin, polysorbate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, at least one aqueous solution of ethanol.

Preferably, the disintegrant is selected from the group consisting of microcrystalline cellulose; the filler is selected from the group consisting of mannitol; the binder is selected from the group consisting of copolyvidone; the lubricant is selected from the group consisting of silica gel; the flavoring agent is selected from the group consisting of sucralose; The aqueous solution of glycerol, polysorbate, and copolyvidone is preferably added in an amount of 0.2 to 4%, 0.1 to 2%, or 1 to 5% by mass of the aqueous solution of glycerin, polysorbate, and copolyvidone.

Preferably, the copovidone is selected from the group consisting of Plasdone S-630, the disintegrant is selected from the group consisting of microcrystalline cellulose PH101, the cesium carbonate is selected from the group consisting of micronized cesium carbonate, and the polysorbate is selected from the group consisting of polysorbate 80.

The tablet of the orally rapidly disintegrating tablet has a weight of 1 to 2.5 g, and the proportion of strontium carbonate is 40 to 70%.

Preferably, the orally rapidly disintegrating tablet has a tablet weight of 0.5 to 4 g, wherein the strontium carbonate ratio is 25 to 80%.

The oral rapid disintegrating tablet is made by using a pharmaceutical grade original powder and a binder by using a liquid 3D printing method, as follows:

A 3D printing technology for preparing an oral rapid disintegrating tablet for treating hyperphosphatemia, comprising the following steps:

1) 30 to 75% of strontium carbonate, 5 to 30% of disintegrant, 2 to 40% of filler, 0 to 20% of diluent, 0 to 25% of sweetener, 1 to 1 by mass fraction 25% of the binder, 0.3 to 3% of the lubricant and 0.05 to 2% of the flavoring agent are uniformly mixed to obtain the powder for printing;

2) preparing a binder, wherein the binder is selected from the group consisting of aqueous ethanol solution, starch solution or added with povidone, copovidone, glycerin, polysorbate, hydroxypropylcellulose, hydroxypropylmethylcellulose At least one aqueous solution of ethanol; in ethanol aqueous solution, the volume percentage of ethanol is 5 to 60%;

3) Software design of 3D printing tablets: design the size of cylindrical orally disintegrating tablets (such as the diameter of the tablets in the range of 15 to 22 mm) and the number of parameters by computer CAD software or Magics software, and convert them into 3D printers. (LTY-200 type) identifiable files in STL format, imported into the 3D printer software system;

4) Using powder 3D printing method, the layer-by-layer powder is made into a three-dimensional structure tablet by using a binder, and the relevant parameters are as follows: the height of the layer is 0.1-0.6 mm, and the number of layers is 10-77. Layer, the number of times of spraying a single layer of liquid is 1 or 2 times, and the amount of the binder is 0.01 to 0.1 times the weight of the powder required for a single tablet;

5) The tablet is naturally left to stand for 15 to 60 minutes; then placed in an oven at 30 to 70 ° C for 1 to 2.5 hours to obtain an orally rapidly disintegrating tablet for treating hyperphosphatemia.

Can also be as follows:

1) 25 to 80% of strontium carbonate, 1 to 35% of disintegrant, 1 to 40% of filler, 0 to 30% of diluent, 0 to 25% of sweetener, 0.5 to 0.5% by mass. 35% of the binder, 0.1 to 5% of the lubricant and 0.01 to 5% of the flavoring agent are uniformly mixed to obtain the powder for printing;

2) preparing a binder, wherein the binder is selected from the group consisting of a sucrose solution, a sodium alginate solution, an aqueous ethanol solution, an aqueous methanol solution, a starch solution, an aqueous methylcellulose solution, an aqueous sodium carboxymethylcellulose solution, and/or a polyaddition An aqueous solution of at least one of ketene, copolyvidone, glycerin, polysorbate, hydroxypropylcellulose, hydroxypropylmethylcellulose;

3) software design of three-dimensional printing tablet: design the relevant parameters of the strontium carbonate orally disintegrating tablet by computer software, convert it into a file readable by the 3D printer, and import it into the 3D printer software system; wherein the printing parameter Including the shape, size and number of strontium carbonate orally disintegrating tablets.

4) Using powder 3D printing method, the layer-by-layer powder is made into a three-dimensional structure tablet by using a binder, and the relevant parameters are as follows: the height of the layer is 0.01 to 1 mm, and the number of layers is 10 to 80 layers. The number of times of spraying the single layer of the adhesive is 1 to 5 times, and the amount of the binder is 0.01 to 1 times the weight of the powder required for the individual tablets;

5) The tablet is naturally aired for a period of time; then placed in an oven for a period of time to obtain an orally rapidly disintegrating tablet for treating hyperphosphatemia.

Preferably, the binder is prepared by dissolving glycerin, polysorbate and copovidone in the aqueous ethanol solution with a preferred mass fraction of 5 to 60% aqueous ethanol as a solvent, preferably glycerin in the binder. The mass fraction of polysorbate and copolyvidone is 0.2 to 4%, 0.1 to 2%, and 1 to 5%, respectively.

Preferably, the cerium carbonate and mannitol are sieved before mixing, preferably 100-200 mesh, and the cerium carbonate is dried in an oven for a period of time before sieving, preferably in an oven at 30-70 ° C for 5-40 minutes. .

The beneficial effects of the present invention are embodied in:

The content ratio of the oral rapid disintegrating tablet formula of the invention effectively controls the drug loading amount as well as the hardness and disintegration, and the added flavoring agent makes the drug have a good mouthfeel when taken. The oral rapid disintegrating tablet is made by a 3D printing process, and has a simple preparation process and a high single tablet amount compared with the conventional tableting process. The tablet has a porous water-soluble matrix and can be quickly dissolved in water, and the disintegration time limit is in accordance with the pharmacopoeia. Requires that the disintegration time is 2 to 60 seconds, bringing a new oral experience to patients. Through experiments, the hardness of the orally rapidly disintegrating tablet of the present invention is up to about 10 kg, and the hardness is effectively ensured while having a high drug loading amount, and the foundation for individualized and precise medicine is laid, and the market has a very high market. Application prospects.

DRAWINGS

Fig. 1 is a schematic view showing the positive (a) and reverse (b) sides of a strontium carbonate 3D printed tablet.

detailed description

The invention is further described in conjunction with the accompanying drawings and embodiments, which are merely illustrative and not restrictive.

Example 1:

(1) prescription (tablet)

Note: The amount of each component added in the prescription is ±0.1g based on the current amount.

(2) 3D printing process:

1) The cesium carbonate raw material (micronized cerium carbonate raw material) and mannitol are weighed through a 150 mesh sieve before the viscous powder (mainly strontium carbonate) is placed in a 50 ° C oven before sieving. 5 to 20 minutes, preferably 15 minutes, to facilitate mixing of the more viscous powder;

2) Mix the prepared powder, mix well and mix to obtain the drug powder, ready to print;

3) Preparation of binder (spray solution): 10% ethanol + (1.0% glycerol, 0.5% polysorbate 80) + 2% Plasdone S-630 as binder; ie binder in 10% by volume of ethanol The aqueous solution is a solvent, and glycerin, polysorbate 80, and Plasdone S-630 are dissolved therein, and the mass fractions of glycerin, polysorbate 80, and Plasdone S-630 in the binder are 1.0%, 0.5%, and 2%, respectively;

4) Software design for 3D printing tablets:

The parameters such as the size and number of the strontium carbonate orally disintegrating tablets are designed by computer software, and converted into files in a format recognizable by the 3D printer, and imported into the 3D printer software system;

Preferably, the size and quantity of the cylindrical orally disintegrating tablet are designed by computer CAD software or Magics software, and converted into a file of the STL format recognizable by the 3D printer (LTY-200 type), and imported into the 3D printer software system. ;

5) Adding adhesive to the liquid jet cartridge, using 3D printing technology, layer by layer printing to make three-dimensional structure tablets (ie layer-by-layer powder coating, spraying adhesive at the interlayer production position), layer height 0.13mm a single layer of liquid spray 2 times, the number of layers of 42; the amount of the binder in a single tablet is 0.01 to 1 times, preferably 0.01 to 0.1 times the weight of the drug powder;

6) printing formed tablets are left open for 30 minutes; then placed in an oven at 50 ° C, drying time is 0.5 ~ 2h, preferably 1.5 ~ 2h;

7) Packing after drying the tablets; see Figure 1, the structural characteristics of the tablets are as follows:

Front: The surface is smooth (due to the last time the powder is sprayed with adhesive) and is not easily broken.

The reverse side: the porous substrate bottom layer, the whole tablet is a network structure; when placed in a small amount of water, the tablet can be quickly disintegrated by utilizing the capillary phenomenon.

After testing: the tablet weight was 0.98g (close to 1g), the hardness of the tablet was measured by YD-II hardness tester was 0.78kg, and the time limit of disintegration measured by ZB-1C intelligent disintegrator was: 4~10 seconds.

Example 2:

(1) prescription (tablet)

(2) 3D printing process

The conditions are the same as in the first embodiment;

Tested: the tablet weight is 1.08g, the hardness is 3.48kg, and the disintegration time limit is: 3-7 seconds.

Example 3:

(1) prescription (tablet)

(2) 3D printing process

The same as Embodiment 1 except for the following conditions:

1 single layer spray 2 times, the number of layers is 61;

Tested: the tablet weight is 1.62g, the hardness is 4.71kg, and the disintegration time limit is: 4~5 seconds.

Example 4:

(1) prescription (tablet)

(2) 3D printing process

The conditions are the same as in the first embodiment;

Tested: tablet weight 1.16g, hardness 2.36kg, disintegration time limit: 4 ~ 7 seconds.

Example 5:

(1) prescription (tablet)

(2) 3D printing process

The same as Embodiment 1 except for the following conditions:

The number of layers is 61, and the single layer is sprayed twice;

Tested: tablet weight 1.56g, hardness 3.32kg, disintegration time limit: 7 ~ 9 seconds.

The strontium carbonate 3D printing tablet of the present invention is used orally.

Experiments show that the strontium carbonate 3D printing tablet of the invention has a large drug loading amount (25 to 80% of the main material of strontium carbonate in a single tablet), is easy to disintegrate, has high hardness, and is convenient to take and tastes good. It can maintain rapid disintegration performance even under high dose load, and can completely disintegrate within 60 seconds, which meets the Chinese Pharmacopoeia's disintegration time limit (Chinese Pharmacopoeia's measurement standard: all disintegration within 15 minutes) . It is suitable for the treatment of hyperphosphatemia in patients with chronic renal failure.

It is to be understood that the above description of the specific embodiments is in no way intended to be construed as limiting the scope of the invention.

Claims

A rapid disintegrating tablet for treating hyperphosphatemia prepared by a 3D printing technique, characterized in that the oral disintegrating tablet comprises a pharmaceutical grade raw powder component and a binder, and the pharmaceutical grade raw powder group According to the mass percentage, 30 to 75% of strontium carbonate, 5 to 30% of disintegrant, 2 to 40% of filler, 0 to 20% of diluent, 0 to 25% of sweetener, 1 to 25% of the binder, 0.3 to 3% of the lubricant and 0.05 to 2% of the flavoring agent; the amount of the binder in the tablet is 0.01 to 0.1 times the weight of the pharmaceutical grade raw powder component.
A rapid disintegrating tablet for treating hyperphosphatemia prepared by a 3D printing technique, characterized in that the oral disintegrating tablet comprises a pharmaceutical grade raw powder component and a binder, and the pharmaceutical grade raw powder group The mass percentage includes: 30 to 75% strontium carbonate, 5 to 30% disintegrant, 2 to 40% filler, 0 to 20% diluent, 0 to 25% sweetener, 1 to 25% of the binder, 0.3 to 3% of the lubricant and 0.05 to 2% of the flavoring agent; the amount of the binder in the tablet is 0.01 to 0.1 times the weight of the pharmaceutical grade raw powder component.
A rapid disintegrating tablet for treating hyperphosphatemia prepared by a 3D printing technique, characterized in that the oral disintegrating tablet comprises a pharmaceutical grade raw powder component and a binder, and the pharmaceutical grade raw powder group According to the mass percentage, 25 to 80% of barium carbonate, 1 to 35% of disintegrant, 1 to 40% of filler, 0 to 30% of diluent, 0 to 25% of sweetener, 0.5 to 35% of the binder, 0.1 to 5% of the lubricant and 0.01 to 5% of the flavoring agent; the amount of the binder in the tablet is 0.01 to 1 times the weight of the pharmaceutical grade raw powder component.
The orally rapidly disintegrating tablet according to claim 1 or 2 or 3, wherein the disintegrating agent is selected from the group consisting of microcrystalline cellulose, dry starch or alginic acid; and the filler is selected from the group consisting of starch, dextrin, mannitol or Sorbitol; the diluent is selected from the group consisting of lactose; the sweetener is selected from the group consisting of sucrose; and the binder is selected from the group consisting of povidone, copovidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or ethyl a cellulose; the lubricant is selected from the group consisting of magnesium stearate, micronized silica gel or talc; the flavoring agent is selected from the group consisting of sucralose or powdered sugar; the binder is selected from the group consisting of aqueous ethanol solution, starch solution or added poly An aqueous solution of at least one of ketene, copolyvidone, glycerin, polysorbate, hydroxypropylcellulose, and hydroxypropylmethylcellulose; preferably, the aqueous ethanol solution has a volume percentage of ethanol of 5 to 60%.
The orally rapidly disintegrating tablet according to claim 1 or 2 or 3, wherein the disintegrating agent is selected from the group consisting of microcrystalline cellulose, dry starch, alginic acid, protein powder, sodium sea oxalate, low-substituted hydroxypropyl cellulose, One or more of crospovidone, carboxymethylcellulose calcium and/or sodium carboxymethylcellulose; the filler is selected from the group consisting of starch, dextrin, mannitol and/or sorbitol Or a plurality of; the diluent is selected from one or more of the group consisting of lactose, calcium hydrogen phosphate, calcium carbonate and/or calcium sulfate; and the sweetener is selected from the group consisting of sucrose and/or acesulfame. One or more; the binder is selected from the group consisting of povidone, copovidone, gelatin, methyl ether cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and/or ethyl cellulose. One or more; the lubricant is selected from one or more of magnesium stearate, fine powder silica gel and/or talc powder; the flavoring agent is selected from the group consisting of sucralose and/or rock sugar powder, etc. One or more of the binders; the binder is selected from the group consisting of a sucrose solution, a sodium alginate solution, an aqueous ethanol solution, an aqueous methanol solution, a starch solution, and an aqueous methyl cellulose solution. An aqueous solution of sodium carboxymethylcellulose and/or an aqueous solution of ethanol added with at least one of povidone, copolyvidone, glycerin, polysorbate, hydroxypropylcellulose, and hydroxypropylmethylcellulose.
The orally rapidly disintegrating tablet according to claim 1 or 2 or 3, wherein the disintegrant is selected from the group consisting of microcrystalline cellulose; the filler is selected from the group consisting of mannitol; the binder is selected from the group consisting of copolyvidone; Self-micronized silica gel; the flavoring agent is selected from the group consisting of sucralose; the binder is selected from the group consisting of aqueous solutions of ethanol added with glycerin, polysorbate and copolyvidone, preferably the final concentration of glycerol, polysorbate, copovidone by mass fraction It is 0.2 to 4%, 0.1 to 2%, and 1 to 5% in this order.
The orally rapidly disintegrating tablet according to claim 4 or 5 or 6, wherein the copovidone is selected from the group consisting of Plasdone S-630, the disintegrant is selected from the group consisting of microcrystalline cellulose PH101, and the cesium carbonate is selected from the group consisting of micronized Barium carbonate, polysorbate is selected from polysorbate 80.
The orally rapidly disintegrating tablet according to claim 1 or 2 or 3, wherein the orally disintegrating tablet has a tablet weight of 1 to 2.5 g, and the strontium carbonate ratio is 40 to 70%.
The orally rapidly disintegrating tablet according to claim 1 or 2 or 3, wherein the orally disintegrating tablet has a tablet weight of 0.5 to 4 g, and the strontium carbonate ratio is 25 to 80%.
The orally rapidly disintegrating tablet according to claim 1 or 2 or 3, wherein the orally disintegrating tablet is produced by using a pharmaceutical grade raw powder and a binder by a powder liquid 3D printing method.
A method for preparing a rapid disintegration tablet for treating hyperphosphatemia by using a 3D printing technique, comprising: the following steps:

1) 30 to 75% of strontium carbonate, 5 to 30% of disintegrant, 2 to 40% of filler, 0 to 20% of diluent, 0 to 25% of sweetener, 1 to 1 by mass fraction 25% of the binder, 0.3 to 3% of the lubricant and 0.05 to 2% of the flavoring agent are uniformly mixed to obtain the powder for printing;

2) preparing a binder, wherein the binder is selected from the group consisting of aqueous ethanol solution, starch solution or added with povidone, copovidone, glycerin, polysorbate, hydroxypropylcellulose, hydroxypropylmethylcellulose At least one aqueous solution of ethanol; preferably, in an aqueous ethanol solution, the volume percentage of ethanol is 5 to 60%;

3) Using powder 3D printing method, the powder layered by layer is made into three-dimensional structure tablets by using adhesive, and the relevant parameters are as follows: the height of the layer is 0.1-0.6mm, and the number of layers is 10-77. Layer, the number of times of spraying a single layer of liquid is 1 or 2 times, and the amount of the binder is 0.01 to 0.1 times the weight of the powder required for a single tablet;

4) The tablet is naturally left to stand for 15 to 60 minutes; then placed in an oven at 30 to 70 ° C for 1 to 2.5 hours to obtain an orally rapidly disintegrating tablet for treating hyperphosphatemia.
A method for preparing a rapid disintegration tablet for treating hyperphosphatemia by using a 3D printing technique, comprising: the following steps:

1) 25 to 80% of strontium carbonate, 1 to 35% of disintegrant, 1 to 40% of filler, 0 to 30% of diluent, 0 to 25% of sweetener, 0.5 to 0.5% by mass. 35% of the binder, 0.1 to 5% of the lubricant, and 0.01 to 5% of the flavoring agent are uniformly mixed to obtain the powder for printing;

2) preparing a binder, wherein the binder is selected from the group consisting of a sucrose solution, a sodium alginate solution, an aqueous ethanol solution, an aqueous methanol solution, a starch solution, an aqueous methylcellulose solution, an aqueous sodium carboxymethylcellulose solution, and/or a polyaddition An aqueous solution of at least one of ketene, copolyvidone, glycerin, polysorbate, hydroxypropylcellulose, hydroxypropylmethylcellulose;

3) Using powder 3D printing method, the layer-by-layer powder is made into a three-dimensional structure tablet by using a binder, and the relevant parameters are as follows: the height of the layer is 0.01 to 1 mm, and the number of layers is 10 to 80 layers. The number of times of spraying the single layer of the adhesive is 1 to 5 times, and the amount of the binder is 0.01 to 1 times the weight of the powder required for the individual tablets;

4) The tablet is naturally aired for a period of time; then placed in an oven for a period of time to obtain an orally rapidly disintegrating tablet for treating hyperphosphatemia.
The method according to claim 11 or 12, wherein the disintegrant is selected from the group consisting of microcrystalline cellulose, dry starch or alginic acid; the filler is selected from the group consisting of starch, dextrin, mannitol or sorbitol; Selected from lactose; the sweetener is selected from sucrose; the binder is selected from the group consisting of povidone, copovidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or ethylcellulose; the lubricant is selected from magnesium stearate , micronized silica gel or talc; the flavoring agent is selected from the group consisting of sucralose or powdered sugar; the binder is selected from the group consisting of glycerin, polysorbate and copolyvidone in ethanol, preferably glycerol, polysorbate, copovidone The final concentration is 0.2 to 4%, 0.1 to 2%, and 1 to 5% in terms of mass fraction.
The method according to claim 11 or 12, wherein the disintegrant is selected from the group consisting of microcrystalline cellulose, dry starch, alginic acid, protein powder, sodium alginate, low-substituted hydroxypropyl cellulose, and cross-linked polycondensation. One or more of ketene, carboxymethylcellulose calcium and/or sodium carboxymethylcellulose; the filler is selected from one or more of starch, dextrin, mannitol and/or sorbitol; One or more of lactose, calcium hydrogen phosphate, calcium phosphate and/or calcium sulfate; the sweetener is selected from one or more of sucrose and/or acesulfame; the binder is selected from the group consisting of povidone, One or more of copolyvidone, gelatin, methyl ether cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose or ethyl cellulose; the lubricant is selected from magnesium stearate micro-silica gel and/or One or more of talc powder; the flavoring agent is selected from one or more of sucralose and/or rock sugar powder; and the binder is selected from the group consisting of aqueous solutions of ethanol added with glycerin, polysorbate and copovidone.
The method according to claim 11 or 12, wherein the binder is prepared by dissolving glycerin, polysorbate and copovidone with a preferred mass fraction of 5 to 60% aqueous ethanol as a solvent. In the aqueous ethanol solution, the mass fraction of glycerin, polysorbate, and copolyvidone in the binder is preferably 0.2 to 4%, 0.1 to 2%, or 1 to 5%.
The method according to claim 13 or 14, wherein the cerium carbonate and mannitol are passed through a mesh before mixing, and the cerium carbonate is dried in an oven for a certain period of time before sieving.
The method according to claim 13 or 14, wherein the cerium carbonate and mannitol are passed through a sieve of 100 to 200 mesh before mixing, and the cerium carbonate is placed in an oven at 30 to 70 ° C for 5 to 5 before sieving. 40 minutes.
The method according to claim 11 or 12, wherein the copolyvidone is selected from the group consisting of Plasdone S-630, the microcrystalline cellulose is selected from the group consisting of microcrystalline cellulose PH101, and the cesium carbonate is selected from the group consisting of micronized cesium carbonate. The sorbate is selected from the group consisting of polysorbate 80.