A silicon dioxide-based medicinal blank pill core and preparation method thereof

Abstract

The present invention relates to the field of medical preparations, and discloses a silicon dioxide-based medicinal blank pill core and a preparation method thereof. The preparation method comprises the following steps: S1: mixing precipitated silicon dioxide, microcrystalline cellulose and colloidal silicon dioxide, and adding water to moisten to obtain a mixed powder; S2: mixing colloidal silicon dioxide with water to obtain a colloidal silicon dioxide dispersion; S3: conveying the mixed powder to a centrifugal granulation device, spraying the colloidal silicon dioxide dispersion, performing centrifugal granulation, and drying to obtain a silicon dioxide-based medicinal blank pill core with a silicon dioxide content higher than 70%. The preparation method of the present invention can ensure that the blank pill core has a high mechanical strength, and the silicon dioxide content in the blank pill core obtained by the centrifugal granulation method can reach more than 70%.

Description

Technical Field

[0001] The invention relates to the field of medical preparations, and in particular to a silicon dioxide-based medicinal blank pill core and a preparation method thereof. Background Art

[0002] Micropellets refer to spherical or quasi-spherical oral dosage forms with a diameter of generally about 1 mm and no more than 2.5 mm, which can be used as drug carriers to fill capsules or be pressed into tablets. Blank pellet cores can be used directly as drug carriers, or as mold cores for preparing drug-containing micropellets. Traditional blank pellet cores mainly include sugar pellets, microcrystalline cellulose pellet cores, and starch pellet cores. Their bulk density is relatively high, which makes it difficult to meet the requirements of small-dose drug loading capsules and floating gastric retention drug delivery systems.

[0003] The blank silica pellet core uses silica as the main material, which can reduce the bulk density of the blank pellet core, thereby increasing its drug loading, which is conducive to meeting the requirements of drug-loaded micro-dose capsules, and is also conducive to floating in gastric juice, prolonging the retention time of the drug in the stomach without affecting gastric emptying. However, the bonding between silica particles is weak, and a certain amount of microcrystalline cellulose needs to be added as a binder to make the blank pellet core have sufficient mechanical strength and not easy to break during storage, transportation and drug loading. A higher content of microcrystalline cellulose will cause the following problems: the interaction between microcrystalline cellulose and the API will affect the release rate of the API. For some drugs that need to take effect quickly, a too slow release rate will affect their therapeutic effect; and the interaction between microcrystalline cellulose and some APIs will affect the chemical stability of the API, reducing the shelf life and efficacy of the drug; in addition, due to the surface properties and structural characteristics of microcrystalline cellulose, it may also hinder the uniform adhesion of the coating material on the surface of the pellet core.

[0004] Patent CN114028577A discloses a silica pellet core and a preparation method thereof. After silica and microcrystalline cellulose are mixed and ground, the silica pellet core is made by extrusion, spheronization and fluidized drying. In this patent, the proportion of silica in the silica pellet core is up to 80%. When the proportion of silica is higher than 80%, it will cause excessive brittleness, that is, the mechanical strength of the pellet core is too low. Compared with the granulation method (extrusion, spheronization and fluidization) used in this patent, the centrifugal granulation method has the advantages of fast pelleting speed, good fluidity and compressibility of the prepared pills, high degree of automation, relatively clean operating environment, and low energy consumption. However, when the centrifugal granulation method is used to prepare the silica pellet core, more microcrystalline cellulose needs to be added to form the pellet and have sufficient mechanical strength. At present, according to experiments, when the centrifugal granulation method is used, the proportion of silica in the blank silica pellet core can only reach 70% at most. When the proportion of silica is higher than 70%, the pellet core is very easy to break. Summary of the invention

[0005] In order to solve the above technical problem, that is, when preparing silica-based blank pill cores by centrifugal granulation, more microcrystalline cellulose needs to be added to make the prepared blank pill cores have sufficient mechanical strength, the present invention provides a silica-based blank pill core and a preparation method thereof. The preparation method of the present invention can effectively improve the brittleness of the silica-based blank pill cores, and can ensure that the blank pill cores have high mechanical strength, so that the silica content in the blank pill cores obtained by centrifugal granulation method reaches more than 70%.

[0006] The specific technical scheme of the present invention is:

[0007] In a first aspect, the present invention provides a method for preparing a silica-based medicinal blank pill core, comprising the following steps:

[0008] S1: Mix precipitated silicon dioxide, microcrystalline cellulose and colloidal silicon dioxide, and add water to moisten to obtain a mixed powder;

[0009] S2: mixing colloidal silica with water to obtain a colloidal silica dispersion;

[0010] S3: conveying the mixed powder to a centrifugal granulation device, spraying the colloidal silica dispersion, performing centrifugal granulation, and drying to obtain a silica-based medicinal blank pellet core having a silica content of more than 70%;

[0011] The ratio of the mass of microcrystalline cellulose in step S1, the mass of precipitated silicon dioxide in step S1, and the total mass of colloidal silicon dioxide in steps S1 and S2 is 1:4-17.5:0.5-3;

[0012] The mass ratio of the colloidal silica in step S1 to the mass ratio of the colloidal silica in step S2 is 1:0.1-9.

[0013] The present invention can effectively improve the brittleness of the silica-based blank pill core by introducing colloidal silica into the blank pill core and combining it with a specific preparation method. The content of silica (including precipitated silica and colloidal silica) in the blank pill core obtained by the centrifugal granulation method can reach more than 70% while ensuring that the blank pill core has a high mechanical strength. Specifically:

[0014] (1) During the centrifugal granulation in step S3, the masterbatch is used as the mother core, and the precipitated silica, microcrystalline cellulose and colloidal silica are gradually wrapped around the masterbatch. In this process, the water molecules contained in the mixed powder and the colloidal silica dispersion can promote the hydrogen bonding between silica and microcrystalline cellulose. At the same time, the colloidal silica has a gelling effect, which can enhance the hydrogen bonding and van der Waals force between the raw materials, thereby forming a spherical blank pellet core and making it have a higher mechanical strength.

[0015] (2) The present invention adds colloidal silicon dioxide in two parts. One part is mixed with precipitated silicon dioxide and microcrystalline cellulose to form a mixed powder, and the other part is prepared into a dispersion and sprayed into the pellet during centrifugal granulation. This can provide sufficient wetting for the colloidal silicon dioxide, which is beneficial for the formation of hydrogen bonds and van der Waals forces. At the same time, the colloidal silicon dioxide can be better dispersed in the blank pill core, thereby further improving the mechanical strength of the blank pill core.

[0016] In addition to the characteristics of high silicon dioxide ratio and high mechanical strength, the blank pill core prepared by the method of the present invention also has a lower bulk density, can float in gastric juice and water, and thus can meet the requirements of a floating gastric retention drug delivery system, and can be used to load nutrients required by aquatic animals, and can be suspended in water after being put into water, so that animals can ingest it. In addition, the blank pill core prepared by the present invention also has a higher water absorption. In addition to medicinal use, the blank pill core prepared by the present invention can also be used in the fields of environmental wastewater treatment, aquatic bait, food, pesticides, etc.

[0017] Preferably, in step S2, the temperature of the water is 25-60°C, and the prepared colloidal silica dispersion is kept warm until used in step S3.

[0018] Furthermore, in step S3, during the whole or part of the centrifugal granulation process, the colloidal silica dispersion used is prepared according to the following conditions: in step S2, the temperature of the water is 40-50°C, and the prepared colloidal silica dispersion is kept warm until used in step S3.

[0019] The present invention finds that, compared with using water at room temperature (25°C), within a certain range, by increasing the water temperature, the gel binding force formed by colloidal silica can be made greater, which is beneficial to improving the binding strength between the raw materials, thereby improving the mechanical strength of the blank pill core; but the higher the water temperature, the better the effect. When the water temperature is too high, the colloidal silica dispersion will form a strong binding force before contacting the mixed powder, making it difficult for this part of the colloidal silica to combine well with precipitated silica and microcrystalline cellulose, thus adversely affecting the mechanical strength of the blank pill core. The present invention uses water with a temperature of 40 to 50°C to prepare the colloidal silica dispersion, which can give the blank pill core a higher mechanical strength.

[0020] Preferably, in step S3, during the whole or part of the centrifugal granulation process, the mixed powder and colloidal silica dispersion used are prepared according to the following conditions: the ratio of the mass of the colloidal silica in step S1 to the mass of the colloidal silica in step S2 is 1:0.1-4.

[0021] Furthermore, in step S3, during the whole or part of the centrifugal granulation process, the mixed powder and colloidal silica dispersion used are prepared according to the following conditions: the ratio of the mass of the colloidal silica in step S1 to the mass of the colloidal silica in step S2 is 1:0.25~1.

[0022] The ratio between the two parts of colloidal silica will affect the mechanical strength of the blank pill core. Under the condition of controlling the total amount of colloidal silica unchanged, when too much colloidal silica is added to the mixed powder, the colloidal silica will not be fully wetted, and its effect of improving the bonding strength between the raw materials will be poor, thus causing the blank pill core to have a low mechanical strength; when too much colloidal silica is used to make a dispersion, the colloidal silica in the dispersion will gel and will not be easily dispersed into the blank pill core, which will also cause the blank pill core to have a low mechanical strength. The present invention, on the basis of adding the colloidal silica in two parts, can improve the mechanical strength of the blank pill core to a greater extent by controlling the mass ratio of the two parts of colloidal silica to 1:0.1~4, and the further preferred mass ratio is 1:0.25~1.

[0023] Furthermore, the process of partial centrifugal granulation is: a centrifugal granulation process after the particle size grows to a target particle size, and the target particle size is no more than 500 μm.

[0024] Preferably, in step S1, the ratio of the total mass of the precipitated silica, microcrystalline cellulose and colloidal silicon dioxide to the mass of water is 2-4:1.

[0025] Preferably, in step S3, the mass ratio of the mixed powder to the colloidal silicon dioxide dispersion is 1:0.6-2.

[0026] Preferably, in step S3, during the centrifugal granulation process, the turntable speed is 20-30 Hz, and the air source pressure is 0.1-0.5 MPa; and the drying process is carried out by boiling drying method.

[0027] Preferably, the particle size of the silica-based medicinal blank pellet core is not greater than 2500 μm.

[0028] In a second aspect, the present invention provides a silica-based medicinal blank pill core prepared by the preparation method.

[0029] Compared with the prior art, the present invention has the following advantages:

[0030] (1) The present invention uses precipitated silica, colloidal silica and microcrystalline cellulose in the blank pill core, and adds the colloidal silica in two specific parts, which can effectively improve the brittleness of the silica-based blank pill core. While ensuring that the blank pill core has a high mechanical strength, the silica content in the blank pill core obtained by the centrifugal granulation method exceeds the limit of 70%;

[0031] (2) The present invention can further improve the mechanical strength of the blank pellet core by controlling the ratio between the two parts of colloidal silica and the water temperature used in preparing the colloidal silica dispersion. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is a photo of the blank pellet core prepared in Example 1 taken under a microscope.

[0033] Figure 2 This is a photo of the blank pellet core prepared in Example 2 taken under a microscope. DETAILED DESCRIPTION

[0034] The present invention will be further described below in conjunction with the embodiments.

[0035] A method for preparing a silica-based medicinal blank pill core comprises the following steps:

[0036] S1: Mix precipitated silicon dioxide, microcrystalline cellulose and colloidal silicon dioxide, and add water to moisten to obtain a mixed powder;

[0037] S2: mixing colloidal silica with water to obtain a colloidal silica dispersion;

[0038] S3: conveying the mixed powder to a centrifugal granulation device, spraying the colloidal silica dispersion, performing centrifugal granulation, and drying to obtain a silica-based medicinal blank pellet core having a silica content of more than 70%;

[0039] The ratio of the mass of microcrystalline cellulose in step S1, the mass of precipitated silicon dioxide in step S1, and the total mass of colloidal silicon dioxide in steps S1 and S2 is 1:4-17.5:0.5-3;

[0040] The mass ratio of the colloidal silica in step S1 to the mass ratio of the colloidal silica in step S2 is 1:0.1-9.

[0041] In some specific embodiments, in step S1, the ratio of the total mass of the precipitated silica, microcrystalline cellulose and colloidal silicon dioxide to the mass of water is 2-4:1.

[0042] In some specific embodiments, in step S2, the temperature of the water is 25-60°C, and the prepared colloidal silica dispersion is kept warm until used in step S3.

[0043] In some specific embodiments, in step S3, during the whole or part of the centrifugal granulation process, the colloidal silica dispersion used is prepared according to the following conditions: in step S2, the temperature of the water is 40-50°C, and the prepared colloidal silica dispersion is kept warm until used in step S3. Optionally or preferably, the part of the centrifugal granulation process is a centrifugal granulation process after the particle size grows to a target particle size, and the target particle size is not greater than 500 μm.

[0044] In some specific embodiments, in step S3, the mass ratio of the mixed powder to the colloidal silica dispersion is 1:0.6-2.

[0045] In some specific embodiments, in step S3, in the whole or part of the centrifugal granulation process, the mixed powder and colloidal silica dispersion used are prepared according to the following conditions: the ratio of the mass of colloidal silica in step S1 to the mass of colloidal silica in step S2 is 1:0.1 to 4. Optionally or preferably, the process of partial centrifugal granulation is a centrifugal granulation process after the particle size grows to a target particle size, and the target particle size is not greater than 500 μm.

[0046] In some specific embodiments, in step S3, during the centrifugal granulation process, the turntable speed is 20-30 Hz, and the gas source pressure is 0.1-0.5 MPa.

[0047] In some specific embodiments, in step S3, the drying process is performed by a fluidized bed drying method.

[0048] In some specific embodiments, the particle size of the silica-based pharmaceutical blank pellet core is no greater than 2500 μm.

[0049] In the whole centrifugal granulation process, the present invention can always use the same formula of mixed powder and colloidal silicon dioxide dispersion, or change the formula of mixed powder and colloidal silicon dioxide dispersion as the blank pellet core grows.

[0050] In step S3, a one-step granulation method can be adopted, starting from powder, and directly obtaining blank pill cores with large particle size through centrifugal granulation and drying; or a step-by-step granulation method can be adopted, starting from powder, and obtaining blank pill cores with small particle size through one-step centrifugal granulation and drying, which are stored for standby use, and then the centrifugal granulation and drying process is recycled one or more times, and each centrifugal granulation uses the blank pill core obtained last time as the master particle, and the particle size is enlarged on the basis of the blank pill core to obtain a large particle size blank pill core. There is no obvious difference in the performance of the blank pill cores finally obtained by the above-mentioned one-step granulation and step-by-step granulation methods.

[0051] A silicon dioxide-based medicinal blank pill core prepared by the preparation method.

[0052] The present invention is described below by specific examples. It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of the present invention. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention, and the attached claims and any equivalents thereof are the protection scope of the present invention.

[0053] Unless otherwise defined, all technical terms and scientific terms used in the present invention have the same meanings as those commonly understood by ordinary technicians in the field to which the present disclosure belongs. Unless otherwise specified, the raw materials and equipment used in the present invention are conventional raw materials and equipment in the field and can be obtained from conventional commercial channels; unless otherwise specified, the methods used in the present invention are conventional methods in the field.

[0054] In the following examples and comparative examples, "parts" are all parts by weight.

[0055] Example 1

[0056] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0057] (1) Starting and enlarging ingredients:

[0058] According to the amounts in Table 1, weigh the starting material and the raw materials for primary amplification.

[0059] Table 1 Raw material formula for the starting mother and primary enlargement of Example 1

[0060]

[0061] 65 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 2 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 41 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder I for later use.

[0062] 18 parts of colloidal silica were dispersed in 180 parts of purified water at 25° C. to obtain colloidal silica dispersion I, which was set aside.

[0063] (2) Secondary enlargement ingredients:

[0064] According to the amounts in Table 2, weigh the raw materials for secondary amplification.

[0065] Table 2 Raw material formula for secondary amplification of Example 1

[0066]

[0067] 65.5 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 2 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 40.75 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0068] 17.5 parts of colloidal silica were dispersed in 175 parts of purified water at 25°C to obtain colloidal silica dispersion II, which was used for later use.

[0069] (3) Centrifugal granulation:

[0070] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:1.56, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 1120~2500μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain a wet pellet core.

[0071] (4) Drying:

[0072] The wet pellet cores prepared in step (3) are placed in a fluidized bed dryer, the air inlet temperature is set to 110±5°C, and the drying time is set to 60 min. The heating is turned off and the temperature is automatically lowered. The material is discharged to obtain silica-based medicinal blank pellet cores. The appearance of the blank pellet cores prepared in this example is shown in FIG. Figure 1 .

[0073] Example 2

[0074] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0075] (1) Starting and enlarging ingredients:

[0076] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0077] (2) Secondary enlargement ingredients:

[0078] According to the amounts in Table 3, weigh the raw materials for secondary amplification.

[0079] Table 3 Raw material formula for secondary amplification of Example 2

[0080]

[0081] 85.5 parts of precipitated silicon dioxide, 5 parts of microcrystalline cellulose and 2 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 43.75 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0082] 12.5 parts of colloidal silica were dispersed in 125 parts of purified water at 25° C. to obtain colloidal silica dispersion II, which was used for later use.

[0083] (3) Centrifugal granulation:

[0084] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:1.01, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 710~800μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0085] (4) Drying:

[0086] The wet pellet cores prepared in step (3) are placed in a fluidized bed dryer, the air inlet temperature is set to 110±5°C, and the drying time is set to 60 min. The heating is turned off and the temperature is automatically lowered. The material is discharged to obtain silica-based medicinal blank pellet cores. The appearance of the blank pellet cores prepared in this example is shown in FIG. Figure 2 .

[0087] Example 3

[0088] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0089] (1) Starting and enlarging ingredients:

[0090] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0091] (2) Secondary enlargement ingredients:

[0092] According to the amounts in Table 4, weigh the raw materials for secondary amplification.

[0093] Table 4 Raw material formula for secondary amplification of Example 3

[0094]

[0095] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 2 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 30.7 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0096] 8 parts of colloidal silica were dispersed in 100 parts of purified water at 25° C. to obtain colloidal silica dispersion II, which was set aside.

[0097] (3) Centrifugal granulation:

[0098] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:0.88, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0099] (4) Drying:

[0100] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0101] Example 4

[0102] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0103] (1) Starting and enlarging ingredients:

[0104] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0105] (2) Secondary enlargement ingredients:

[0106] According to the amounts in Table 5, weigh the raw materials for secondary amplification.

[0107] Table 5 Raw material formula for secondary amplification of Example 4

[0108]

[0109] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 5 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 31.7 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0110] 5 parts of colloidal silica were dispersed in 100 parts of purified water at 25° C. to obtain colloidal silica dispersion II, which was set aside.

[0111] (3) Centrifugal granulation:

[0112] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:0.83, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0113] (4) Drying:

[0114] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0115] Example 5

[0116] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0117] (1) Starting and enlarging ingredients:

[0118] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0119] (2) Secondary enlargement ingredients:

[0120] According to the amounts in Table 6, weigh the raw materials for secondary amplification.

[0121] Table 6 Raw material formula for secondary amplification of Example 5

[0122]

[0123] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 8 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 32.7 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0124] 2 parts of colloidal silica were dispersed in 100 parts of purified water at 25° C. to obtain colloidal silica dispersion II, which was set aside.

[0125] (3) Centrifugal granulation:

[0126] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:0.78, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0127] (4) Drying:

[0128] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0129] Example 6

[0130] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0131] (1) Starting and enlarging ingredients:

[0132] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0133] (2) Secondary enlargement ingredients:

[0134] According to the amounts in Table 7, weigh the raw materials for secondary amplification.

[0135] Table 7 Raw material formula for secondary amplification of Example 6

[0136]

[0137] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 9 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 33 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0138] One part of colloidal silica was dispersed in 100 parts of purified water at 25° C. to obtain colloidal silica dispersion II, which was set aside.

[0139] (3) Centrifugal granulation:

[0140] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:0.77, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0141] (4) Drying:

[0142] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0143] Example 7

[0144] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0145] (1) Starting and enlarging ingredients:

[0146] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0147] (2) Secondary enlargement ingredients:

[0148] According to the amounts in Table 5 above, weigh the raw materials for secondary amplification.

[0149] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 5 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 31.7 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0150] 5 parts of colloidal silica were dispersed in 100 parts of purified water at 40°C to obtain colloidal silica dispersion II, which was kept warm for later use.

[0151] (3) Centrifugal granulation:

[0152] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:0.83, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0153] (4) Drying:

[0154] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0155] Example 8

[0156] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0157] (1) Starting and enlarging ingredients:

[0158] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0159] (2) Secondary enlargement ingredients:

[0160] According to the amounts in Table 5 above, weigh the raw materials for secondary amplification.

[0161] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 5 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 31.7 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0162] 5 parts of colloidal silica were dispersed in 100 parts of purified water at 50°C to obtain colloidal silica dispersion II, which was kept warm for later use.

[0163] (3) Centrifugal granulation:

[0164] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:0.83, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0165] (4) Drying:

[0166] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0167] Example 9

[0168] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0169] (1) Starting and enlarging ingredients:

[0170] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0171] (2) Secondary enlargement ingredients:

[0172] According to the amounts in Table 5 above, weigh the raw materials for secondary amplification.

[0173] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 5 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 31.7 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0174] 5 parts of colloidal silica were dispersed in 100 parts of purified water at 60°C to obtain colloidal silica dispersion II, which was kept warm for later use.

[0175] (3) Centrifugal granulation:

[0176] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:0.83, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0177] (4) Drying:

[0178] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0179] Example 10

[0180] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0181] (1) Ingredients:

[0182] Weigh each raw material according to the amount in Table 5 above.

[0183] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 5 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 31.7 parts of purified water at 25° C. were added to moisten the mixture to obtain a mixed powder for later use.

[0184] 5 parts of colloidal silica were dispersed in 100 parts of purified water at 25° C. to obtain a colloidal silica dispersion, which was set aside.

[0185] (2) Centrifugal granulation:

[0186] The turntable of the centrifugal granulator was turned on, the speed was set to 20 Hz, the air source pressure was set to 0.3 MPa, the colloidal silica dispersion was transported to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator. At the same time, the mixed powder was transported to the centrifugal granulator, and the mass ratio of the input mixed powder to the colloidal silica dispersion was controlled to be 1:0.83. Centrifugal granulation was performed until the pellets grew to the target particle size of 600-710 μm, the powder supply and liquid spraying were stopped, polishing was carried out at a main engine speed of 40 Hz for 1 min, and the material was discharged to obtain wet pellet cores.

[0187] (3) Drying:

[0188] The wet pellet core obtained in step (2) is placed in a fluidized bed dryer, the air inlet temperature is set to 110±5°C, and the drying time is set to 60 min. The heating is turned off and the temperature is automatically lowered. The material is discharged to obtain a silica-based medicinal blank pellet core.

[0189] Embodiment 11

[0190] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0191] (1) Preparation of masterbatch:

[0192] In this embodiment, the process of masterbatch batching is the same as the masterbatch preparation and primary amplification batching process in step (1) of embodiment 1. The obtained mixed powder and colloidal silica dispersion are recorded as "mixed powder I" and "colloidal silica dispersion I" for later use.

[0193] The turntable of the centrifugal granulator was turned on, the speed was set to 20 Hz, the air source pressure was set to 0.3 MPa, the colloidal silica dispersion I was transported to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator. At the same time, the mixed powder I was transported to the centrifugal granulator, and the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to a target particle size of 150-250 μm, the powder supply and liquid spraying were stopped, polishing was performed at a main engine speed of 40 Hz for 1 min, and the material was discharged to obtain wet pellet cores and wet masterbatch.

[0194] Place the wet masterbatch in a fluidized bed dryer, set the air inlet temperature to 110±5°C, and set the drying time to 60 minutes. Turn off the heating and cool down automatically. Discharge the material to obtain the silica-based medicinal blank pellet masterbatch, which is stored for later use.

[0195] (2) One-time enlargement of ingredients:

[0196] In this embodiment, the process of one-step scale-up is the same as the process of starting and one-step scale-up in step (1) of embodiment 1. The obtained mixed powder and colloidal silicon dioxide dispersion are recorded as "mixed powder II" and "colloidal silicon dioxide dispersion II" for later use.

[0197] (3) Secondary enlargement ingredients:

[0198] In this embodiment, the process of secondary enlargement and batching is the same as the process of secondary enlargement and batching in step (2) of embodiment 4. The obtained mixed powder and colloidal silicon dioxide dispersion are recorded as "mixed powder III" and "colloidal silicon dioxide dispersion III" for later use.

[0199] (4) Centrifugal granulation:

[0200] The masterbatch prepared in step (1) is placed in a centrifugal granulator, the centrifugal granulator turntable is turned on, the speed is set to 20 Hz, the air source pressure is set to 0.3 MPa, the colloidal silica dispersion II is transported to the spray gun via a peristaltic pump, the liquid in the spray gun is converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder II is transported to the centrifugal granulator at the same time, the mass ratio of the input mixed powder II to the colloidal silica dispersion II is controlled to be 1:1.61, and centrifugal granulation is performed until the pellets grow to a target particle size of 355-500 μm. Then, the input of mixed powder I and colloidal silica dispersion III is stopped, and the mass ratio of the input of mixed powder III and colloidal silica dispersion III is controlled to be 1:0.83, and other conditions remain unchanged until the pellets continue to grow to a target particle size of 600-710 μm, the powder supply and liquid spraying are stopped, and the pellets are polished for 1 min at a main engine speed of 40 Hz, and the pellets are discharged to obtain wet pellet cores.

[0201] (5) Drying:

[0202] The wet pellets prepared in step (4) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0203] Comparative Example 1

[0204] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0205] (1) Ingredients:

[0206] Weigh each raw material according to the amount in Table 8.

[0207] Table 8 Raw material formula of comparative example 1

[0208]

[0209] 70 parts of precipitated silicon dioxide and 30 parts of microcrystalline cellulose were mixed evenly in a mixer, and then 41 parts of purified water at 25° C. were added to moisten the mixture to obtain a mixed powder for later use.

[0210] (2) Centrifugal granulation:

[0211] Turn on the turntable of the centrifugal granulator, set the speed to 20Hz, set the air source pressure to 0.3MPa, and deliver purified water to the spray gun through a peristaltic pump. The compressed air pump converts the liquid in the spray gun into atomized liquid and sprays it into the centrifugal granulator. At the same time, deliver the mixed powder to the centrifugal granulator, control the mass ratio of the input mixed powder to purified water to be 1:1.28, and perform centrifugal granulation until the pellets grow to the target particle size of 600~710μm, stop powder supply and liquid spraying, polish for 1min at a main engine speed of 40Hz, discharge, and obtain wet pellet cores.

[0212] (3) Drying:

[0213] The wet pellet core obtained in step (2) is placed in a fluidized bed dryer, the air inlet temperature is set to 110±5°C, and the drying time is set to 60 min. The heating is turned off and the temperature is automatically lowered. The material is discharged to obtain a silica-based medicinal blank pellet core.

[0214] Comparative Example 2

[0215] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0216] (1) Starting and enlarging ingredients:

[0217] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0218] (2) Secondary enlargement ingredients:

[0219] According to the amounts in Table 9, weigh the raw materials for secondary amplification.

[0220] Table 9 Raw material formula for secondary amplification of Comparative Example 2

[0221]

[0222] 75 parts of precipitated silicon dioxide and 15 parts of microcrystalline cellulose were mixed evenly in a mixer, and then 30 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0223] 10 parts of colloidal silica were dispersed in 100 parts of purified water at 25° C. to obtain colloidal silica dispersion II, which was set aside.

[0224] (3) Centrifugal granulation:

[0225] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and colloidal silica dispersion II were used instead, and the mass ratio of the input of the two was controlled to be 1:0.92, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0226] (4) Drying:

[0227] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0228] Comparative Example 3

[0229] A silica-based pharmaceutical blank pellet core was prepared according to the following steps:

[0230] (1) Starting and enlarging ingredients:

[0231] In this embodiment, the process of preparing the mother and the first-stage amplification is the same as step (1) in embodiment 1, to obtain a mixed powder I and a colloidal silicon dioxide dispersion I for later use.

[0232] (2) Secondary enlargement ingredients:

[0233] According to the amounts in Table 10, weigh the raw materials for secondary amplification.

[0234] Table 10 Raw material formula for secondary amplification of Comparative Example 3

[0235]

[0236] 75 parts of precipitated silicon dioxide, 15 parts of microcrystalline cellulose and 10 parts of colloidal silicon dioxide were mixed uniformly in a mixer, and then 33.3 parts of purified water at 25° C. were added to moisten the mixture to obtain mixed powder II for later use.

[0237] (3) Centrifugal granulation:

[0238] The centrifugal granulator turntable was turned on, the speed was set to 20Hz, the air source pressure was set to 0.3MPa, the colloidal silica dispersion I was delivered to the spray gun via a peristaltic pump, the liquid in the spray gun was converted into atomized liquid by a compressed air pump, and sprayed into the centrifugal granulator, and the mixed powder I was delivered to the centrifugal granulator at the same time, the mass ratio of the input mixed powder I to the colloidal silica dispersion I was controlled to be 1:1.61, and centrifugal granulation was performed until the pellets grew to the target particle size of 355~500μm. Then the input of mixed powder I and colloidal silica dispersion I was stopped, and mixed powder II and purified water were used instead, and the mass ratio of the input of the two was controlled to be 1:0.75, and other conditions remained unchanged until the pellets continued to grow to the target particle size of 600~710μm, the powder supply and liquid spraying were stopped, and the main engine speed was 40Hz for 1min of polishing, and the material was discharged to obtain the wet pellet core.

[0239] (4) Drying:

[0240] The wet pellets prepared in step (3) were placed in a fluidized bed dryer, the air inlet temperature was set to 110±5°C, and the drying time was set to 60 min. The heating was turned off and the temperature was automatically lowered. The material was discharged to obtain silica-based medicinal blank pellets.

[0241] Test Example 1: Physical properties test of blank pellets

[0242] The blank pellet cores prepared according to the methods in the embodiments and comparative examples were tested for performance. The test method is as follows:

[0243] (1) 24-hour swelling rate test method: Use a measuring cylinder to measure 10 mL of the pellet core, record the volume as V1, weigh it, record the weight as W1, add water until the water completely covers the pellet core, leave it for 24 hours, observe the volume of the pellet core, record the volume as V2, pour out the excess water in the measuring cylinder, then use a paper towel to absorb the excess water on the surface of the pellet core, weigh it, record the weight as W2, and calculate the 24-hour swelling rate of the pellet core using the following formula:

[0244] .

[0245] (2) True ball rate detection method: Take a number of pellets and place them under a 40x microscope. Randomly select 60 of them and measure the longest and shortest diameters of the pellets using the two-point method. Calculate the length-to-short diameter ratio of each pellet. Finally, calculate the arithmetic mean of the length-to-short diameter ratios of the 60 pellets.

[0246] (3) Friability test method: Based on the tablet friability test method in the 2020 edition of the Chinese Pharmacopoeia - Part III General Chapter 0923, the pill core and 20 steel balls with a particle size of 3 mm are placed in a cylinder.

[0247] (4) Bulk density test method: Place a stainless steel cup under the chute, and slowly add the powder from a height of 5.1 cm above the funnel into the stainless steel cup through a volume meter (flow down at a suitable speed to prevent blockage. If there is severe blockage on the screen, remove the screen) until the powder overflows. Scrape out the excess powder so that the powder is flush with the cup mouth. Weigh the weight and calculate the bulk density.

[0248] (5) Angle of repose detection method: slowly add the powder from the top of the funnel, and calculate the inclination angle of the conical accumulation formed by the material leaking from the bottom of the funnel on the horizontal plane, which is the angle of repose.

[0249] The performance test results are shown in Table 11.

[0250] Table 11 Physical properties test results of blank pellets

[0251]

[0252] Analyzing the data in Table 11, we can see that:

[0253] (1) According to Examples 1 to 10 and Comparative Example 1, it can be seen that by using the method of the present invention, by adding colloidal silicon dioxide to the blank pill core, it is possible to reduce the amount of microcrystalline cellulose in the blank pill core and increase the proportion of silicon dioxide therein while ensuring that the blank pill core has sufficient mechanical strength (lower friability).

[0254] (2) According to Examples 3 to 6 and Comparative Examples 2 to 3, it can be seen that: while keeping the total amount of colloidal silicon dioxide unchanged, adding it in two parts, one part is mixed with precipitated silicon dioxide and microcrystalline cellulose to form a mixed powder, and the other part is prepared as a dispersion and sprayed into the centrifugal granulation, which can improve the mechanical strength of the blank pill core; and the ratio between the two parts of colloidal silicon dioxide will affect the mechanical strength of the blank pill core. When the ratio is controlled in the range of 1:0.1 to 4, the blank pill core can be given a higher mechanical strength, and more preferably 1:0.25 to 1.

[0255] The reason is analyzed as follows: when the total amount of colloidal silica is controlled unchanged, if too much colloidal silica is added to the mixed powder, or it is only added to the mixed powder without being added in two parts, the colloidal silica will not be fully wetted, and its effect of improving the bonding strength between the raw materials will be poor, thus resulting in lower mechanical strength of the blank pill core; when too much colloidal silica is used to make a dispersion, or it is only prepared into a dispersion without being added in two parts, the colloidal silica in the dispersion will gel and will not be easily dispersed into the blank pill core, thus also resulting in lower mechanical strength of the blank pill core.

[0256] (3) According to Examples 4 and 7-9, it can be seen that when preparing the colloidal silica dispersion, the water temperature used will affect the mechanical strength of the blank pellet cores finally obtained. When the water temperature is 40-50°C, the blank pellet cores can have higher mechanical strength.

[0257] The reason is that within a certain range, by increasing the water temperature, the gel binding force formed by the colloidal silica can be made stronger, which is beneficial to improving the bonding strength between the raw materials, thereby improving the mechanical strength of the blank pill core; but when the water temperature is too high, it will cause the colloidal silica dispersion to form a strong bonding force before it comes into contact with the mixed powder, resulting in this part of the colloidal silica being difficult to combine well with the precipitated silica and microcrystalline cellulose, which will have an adverse effect on the mechanical strength of the blank pill core.

[0258] (4) According to Example 4 and Example 11, it can be seen that: under the same formula, there is no obvious difference in the performance of the blank pill cores finally obtained by using the one-step granulation method (starting from powder, directly preparing blank pill cores with large particle size through centrifugal granulation and drying) and the step-by-step granulation method (starting from powder, preparing blank pill cores with small particle size through the first centrifugal granulation and drying, storing for later use, and then using the blank pill cores with small particle size as masterbatch, and then performing the second centrifugal granulation and drying to obtain blank pill cores with large particle size).

[0259] Test Example 2: Test of the pore distribution of blank pellet core

[0260] The blank pellet core prepared according to the method in Example 4 was tested for pore distribution. The test results are as follows: Using the BET multi-point method (automatic range P / P0=0.0376-0.1987), the specific surface area was measured to be 154.5150 m 2 / g; total pore volume (P / P0=0.990, pore diameter <195.6nm) is 0.7446cm 3 / g; the average pore diameter (4V / A) was measured by BET method to be 17.7525nm; the pore volume and area of ​​each level of pores are shown in Tables 12 and 13.

[0261] Table 12 Test results of pore distribution of blank pellet core (N2 adsorption)

[0262]

[0263] Table 13 Test results of pore distribution of blank pellet core (N2 desorption)

[0264]

[0265] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent transformation made to the above embodiment based on the technical essence of the present invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. A method for preparing SiO2-based medicinal blank pill core, characterized in that: The following steps are involved: S1: Mix precipitated SiO2, microcrystalline cellulose and colloidal SiO2, add water to moisten, and obtain a mixed powder; S2: Mixing colloidal SiO2 with water to obtain a colloidal SiO2 dispersion; S3: conveying the mixed powder to a centrifugal granulation device, spraying the colloidal SiO2 dispersion, centrifugally granulating, and drying to obtain SiO2-based medicinal blank pellet cores with a SiO2 content higher than 70%; The ratio of the mass of microcrystalline cellulose in step S1, the mass of SiO2 prepared by precipitation in step S1, and the total mass of colloidal SiO2 in steps S1 and S2 is 1:4-17.5:0.5-3; The ratio of the mass of colloidal SiO2 in step S1 to the mass of colloidal SiO2 in step S2 is 1:0.1-9.

2. The preparation method according to claim 1, characterized in that: In step S2, the temperature of the water is 25-60°C, and the prepared colloidal SiO2 dispersion is kept warm until used in step S3.

3. The preparation method according to claim 2, characterized in that: In step S3, during the whole or part of the centrifugal granulation process, the colloidal SiO2 dispersion used is prepared according to the following conditions: in step S2, the temperature of the water is 40-50°C, and the prepared colloidal SiO2 dispersion is kept warm until used in step S3.

4. The preparation method according to claim 1, characterized in that: In step S1, the ratio of the total mass of the precipitated SiO2, microcrystalline cellulose and colloidal SiO2 to the mass of water is 2-4:

1.

5. The preparation method according to claim 1, characterized in that: In step S3, the mass ratio of the mixed powder to the colloidal SiO2 dispersion is 1:0.6-2.

6. The preparation method according to claim 1, characterized in that: In step S3, during the centrifugal granulation process, the rotating speed of the turntable is 20-30 Hz, and the air source pressure is 0.1-0.5 MPa.

7. The preparation method according to claim 1, characterized in that: In step S3, the drying process is performed by a fluidized bed drying method.

8. The preparation method according to claim 1, characterized in that: The particle size of the SiO2-based medicinal blank pill core is no more than 2500 μm.

9. A SiO2-based medicinal blank pellet core prepared by the preparation method according to any one of claims 1 to 8.

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