Furosemide tablet and preparation method thereof

Abstract

The invention relates to the technical field of furosemide tablets, in particular to a furosemide tablet and a preparation method thereof. The furosemide tablet is prepared from the following raw materials in parts by weight: 20 to 25 parts of furosemide, 65 to 70 parts of filler, 1.6 to 10 parts of flow aid and 20 to 23 parts of adhesive, the flow aid comprises talcum powder, colloidal silicon dioxide and magnesium stearate. According to the furosemide tablet, the fluidity of furosemide can be improved, the mixing uniformity of the raw materials can be improved, the sticking problem during tabletting can be avoided, the tabletting smoothness can be improved, the dissolution property of the furosemide tablet can be improved, and the dissolution rate of the furosemide tablet can be improved.

Description

Technical Field

[0001] The present invention relates to the technical field of furosemide tablets, and in particular to a furosemide tablet and a preparation method thereof. Background Art

[0002] Furosemide tablets primarily act on the thick ascending limb of the loop of Henle, inhibiting sodium chloride reabsorption and increasing urinary excretion of sodium, potassium, chloride, magnesium, and calcium ions, resulting in a potent diuretic effect. They also dilate renal blood vessels, increasing renal blood flow and providing a protective effect on renal function. The oral absorption rate of furosemide tablets is 60% to 70%. Eating slows absorption but has no effect on absorption or efficacy. In patients with end-stage renal disease, the oral absorption rate drops to 43% to 46%. In patients with edematous conditions such as congestive heart failure and nephrotic syndrome, oral absorption is also reduced due to intestinal edema. In these cases, parenteral administration is often used.

[0003] Chinese patent publication number CN110538157A discloses a furosemide tablet and a preparation method thereof. The furosemide tablet is composed of the following raw materials in parts by weight: 23-25 ​​parts of furosemide, 16-20 parts of corn starch, 50-60 parts of anhydrous lactose, 26-32 parts of purified water, 0.2-2 parts of sodium carboxymethyl starch, and 0.5-1.5 parts of magnesium stearate. The patent does not provide a technical solution for improving the dissolution of furosemide tablets.

[0004] Therefore, providing a furosemide tablet with good solubility and a preparation method thereof is the main technical problem that needs to be solved at present. Summary of the Invention

[0005] In order to solve the above technical problems, the first aspect of the present invention provides a furosemide tablet, wherein the raw materials for its preparation include, by weight, 20-25 parts of furosemide, 65-70 parts of filler, 1.6-10 parts of glidant, and 20-23 parts of binder; the glidant includes talc, colloidal silicon dioxide, and magnesium stearate.

[0006] In one embodiment, the furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0007] In one embodiment, the source of furosemide includes Changzhou Yabang Pharmaceutical Co., Ltd., and the specifications are D90 particle size ≤ 30 μm and D50 particle size ≤ 12 μm.

[0008] In one embodiment, the specific surface area of ​​the talc is 2.41 m 2 / g, with a particle size of 325 meshes. The source of the talc powder includes Guilin Guiguang Talc Development Co., Ltd.

[0009] In order to improve the mixing uniformity of the raw materials, prevent the problem of sticking during tableting, and improve the smoothness of tableting, the inventors found during the experiment that furosemide powder has extremely strong static electricity, is easy to agglomerate, and has no fluidity. In order to improve the mixing uniformity of the raw materials and enhance the dispersion uniformity of furosemide, the inventors found during the experiment that using colloidal silicon dioxide and magnesium stearate as flow aids can improve the fluidity of furosemide and improve the mixing uniformity of the raw materials; using talc as a flow aid can avoid the problem of sticking during tableting and improve the smoothness of tableting.

[0010] In one embodiment, the added amount of magnesium stearate is 0.38-1.25 parts.

[0011] In one embodiment, the added amount of magnesium stearate is 0.75 parts.

[0012] During the experiment, the inventors found that excessive addition of magnesium stearate would increase the disintegration time of furosemide tablets. In order to reduce the disintegration time of furosemide tablets, the inventors found during the experiment that when the addition amount of magnesium stearate was 0.38%-1.25%, the disintegration time of furosemide tablets could be reduced and the dissolution of furosemide tablets could be improved.

[0013] In one embodiment, the filler comprises corn starch and anhydrous lactose.

[0014] In one embodiment, the mass ratio of the corn starch to anhydrous lactose is (0.6-0.8):1.

[0015] During the experiment, the inventors found that corn starch easily absorbs moisture under high humidity conditions, and its dosage has a great influence on the dissolution behavior of furosemide tablets. During the experiment, the inventors creatively discovered that when the mass ratio of corn starch to anhydrous lactose is (0.6-0.8):1, the solubility of furosemide tablets can be improved and the solubility rate of furosemide tablets can be increased; when the proportion of corn starch is high, the amount of sediment when the furosemide tablets are dissolved will increase, thereby reducing the solubility of the furosemide tablets.

[0016] In one embodiment, the filler comprises 27.24 parts of corn starch and 41.92 parts of anhydrous lactose.

[0017] In one embodiment, the glidant comprises 0.6-6.25 parts of talc, 0.63-2.5 parts of colloidal silicon dioxide, and 0.38-1.25 parts of magnesium stearate.

[0018] The glidant comprises 0.63 parts of talc, 2.5 parts of colloidal silicon dioxide, and 0.75 parts of magnesium stearate.

[0019] In one embodiment, the filler consists of corn starch and anhydrous lactose.

[0020] In one embodiment, the adhesive comprises corn starch slurry, the corn starch slurry comprises corn starch and water, and the mass concentration of corn starch in the corn starch slurry is 6%-8%.

[0021] In one embodiment, the binder is corn starch slurry.

[0022] In one embodiment, the corn starch slurry consists of corn starch and water.

[0023] The preparation method of the corn starch slurry comprises the following steps:

[0024] Purified water at 50° C. is added to corn starch and stirred evenly, purified water having a temperature higher than 90° C. is then added and stirred until transparent, and purified water is added to cool the mixture to obtain a corn starch slurry; the amount of purified water added is controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%-8%.

[0025] In one embodiment, the colloidal silica has a particle size of about 15 nm and a specific surface area of ​​200 to 400 m 2 / g.

[0026] A method for preparing furosemide tablets comprises the following steps:

[0027] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0028] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0029] S3 drying, drying the furosemide granules;

[0030] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0031] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0032] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0033] In the S1, furosemide and colloidal silicon dioxide are mixed at a mixing speed of 8-15 rpm and a mixing time of 5-20 min, and are crushed and sieved using a vacuum crushing unit, with a sieve having a mesh size of 60-80.

[0034] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0035] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is (0.6-0.8):1.

[0036] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0037] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 30-40 Hz, the dry mix is ​​added and continued to be mixed for 60 seconds to 130 seconds, and then the adhesive is added to the granulator and stirred and mixed with the mixture for 60 seconds to 130 seconds; the cutter frequency of the granulator is set to 20-40 Hz, and the granulation time is 100-180 seconds.

[0038] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0039] The adhesive is corn starch slurry, which consists of corn starch and water. The mass concentration of corn starch in the corn starch slurry is 6%-8%. The water is purified water.

[0040] The temperature of the binder when added to the granulator is less than 50°C.

[0041] In order to improve the dissolution rate and dissolution rate of furosemide tablets, the inventors discovered during the experiment that a corn starch slurry composed of corn starch and water, wherein the mass concentration of corn starch in the corn starch slurry is 6%-8%; and purified water can improve the dissolution rate and dissolution rate of furosemide tablets. The possible reason is that when the mass concentration of corn starch in the corn starch slurry is maintained at this appropriate concentration, the obtained furosemide granules, after drying, can maintain the material in a particle state, improve the fluidity of the material, and facilitate the subsequent tableting operation, while maintaining a certain looseness, thereby improving the dissolution rate and dissolution rate of the furosemide tablets. However, the mass concentration of corn starch in the corn starch slurry should not be too high. When the mass concentration of corn starch is too high, it will also affect the dissolution rate and dissolution rate of the furosemide tablets.

[0042] In order to improve the dissolution rate and dissolution degree of furosemide tablets, the inventors found during the experiment that when the temperature of the corn starch slurry when added to the granulator is less than 50°C, the dissolution rate and dissolution degree of furosemide tablets can be improved. When the temperature of the corn starch slurry exceeds 50°C, the fluidity of the corn starch slurry will be better, and the furosemide granules obtained when the corn starch slurry is stirred and mixed with the mixture will be denser and firmer, resulting in slower dissolution behavior and reduced dissolution rate of the furosemide tablets.

[0043] The added amount of the adhesive is 20.4%-22.4% of the total mass of the adhesive and the mixture.

[0044] In order to increase the dissolution rate of furosemide tablets, the inventors found during the experiment that when the amount of the binder added is 20.4%-22.4% of the total mass of the binder and the mixture, the dissolution rate of the furosemide tablets can be increased, so that furosemide can be quickly dissolved from the furosemide tablets.

[0045] The total added mass of the binder and the mixture is 34% to 67% of the granulator material loading.

[0046] Granulator material loading capacity = material mass / 0.4 / 2000*100;

[0047] The mass of the material is the total mass of the binder and the mixture, and the bulk density of the material is 0.4 g / mL.

[0048] In one embodiment, the granulator uses a 2L wet granulation pot, and the mixed powder bulk density = 0.4 g / mL is used to calculate the material loading capacity of the granulator; the total mass of the binder and the mixture added is 34%-67% of the material loading capacity of the wet granulation pot of the granulator. In the following examples, the total mass of the binder and the mixture added is used as the material loading capacity of the granulator for description.

[0049] In order to improve the mixing uniformity of the adhesive and the mixture, the inventors found during the experiment that when the total mass of the adhesive and the mixture added is 34%-67% of the material loading capacity of the granulator, the mixing uniformity of the adhesive and the mixture can be improved, and the RSD value of the uniformity of the adhesive and the mixture is less than 3.0%, which can meet the internal control standard and achieve a uniform mixing effect.

[0050] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm.

[0051] The drying temperature in S3 is 60-80° C., and the drying is stopped when the moisture content in the furosemide granules is ≤3.5%.

[0052] The drying temperature in S3 is 68° C. and the drying time is 60 minutes.

[0053] In S4, the furosemide granules dried in S3 are screened and granulated using a 24-mesh stainless steel screen, and then dried to control the moisture content of the furosemide granules to be ≤3.5%. The furosemide granules are then screened and granulated using a 30-mesh stainless steel screen to obtain dry granules.

[0054] When granulating in S4, a 30-mesh stainless steel screen is used to granulate the tablets, so as to control the weight difference of the tablets.

[0055] In S5, when the dry particles and talc are mixed and stirred, the stirring paddle frequency is 35 Hz-40 Hz, and the stirring is performed forward for 30s-60s, reversed for 30s-60s, and then continued to mix for 15 minutes. Then, magnesium stearate is added and stirred and mixed for 8-30 minutes.

[0056] The time for adding magnesium stearate and stirring and mixing includes but is not limited to 8 min, 9 min, 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, 16 min, 17 min, 18 min, 19 min, 20 min, 21 min, 22 min, 23 min, 24 min, 25 min, 26 min, 27 min, 28 min, 29 min, and 30 min.

[0057] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0058] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 30 minutes.

[0059] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 39.4 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0060] The hardness of the furosemide tablets obtained in S6 was 3-6 kg.

[0061] A hardness of 3-6 kg indicates that the furosemide tablets can withstand a pressure of 3-6 kg without breaking or shattering.

[0062] In order to improve the ability of furosemide tablets to maintain a complete tablet shape after transportation and to have good solubility and disintegration, the inventors obtained in the experimental process that the hardness of furosemide tablets is 3-6 kg, which can improve the ability of furosemide tablets to maintain a complete tablet shape after transportation and to have good solubility and disintegration; when the hardness of furosemide tablets is too high, it will affect the friability of furosemide tablets, which will not only reduce the solubility of furosemide tablets, but also be detrimental to the long-term operation of the tablet press, affecting the service life of the tablet press.

[0063] Beneficial effects

[0064] 1. The use of colloidal silicon dioxide and magnesium stearate as glidants in this application can improve the fluidity of furosemide and enhance the mixing uniformity of the raw materials; the use of talc as a glidant can avoid the problem of sticking during tableting and improve the smoothness of tableting.

[0065] 2. The present application uses an addition amount of 0.38%-1.25% of magnesium stearate to reduce the disintegration time of furosemide tablets and improve the dissolution of furosemide tablets.

[0066] 3. When the mass ratio of corn starch and anhydrous lactose used in this application is (0.6-0.8):1, the dissolution of furosemide tablets can be improved and the dissolution rate of furosemide tablets can be increased.

[0067] 4. When the mass concentration of corn starch in the corn starch slurry used in this application is 6%-8%, the dissolution rate and dissolution rate of furosemide tablets can be improved.

[0068] 5. When the amount of binder added in this application is 20.4%-22.4% of the total mass of the binder and the mixture, the dissolution rate of the furosemide tablets can be increased, so that furosemide can be quickly dissolved from the furosemide tablets.

[0069] 6. In this application, when the total mass of the adhesive and the mixture added is 34%-67% of the material loading capacity of the granulator, the mixing uniformity of the adhesive and the mixture can be improved, and the RSD value of the uniformity of the adhesive and the mixture is less than 3.0%, which can meet the internal control standard and achieve a uniform mixing effect.

[0070] 7. The present application limits the hardness of furosemide tablets to 3-6 kg, which can improve the ability of furosemide tablets to maintain the finished tablet shape after transportation and have good solubility and disintegration properties. DETAILED DESCRIPTION

[0071] The sources of the raw materials used in the following examples are shown in Table 1.

[0072] Table 1

[0073]

[0074] Example 1

[0075] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 3.88 parts of a glidant, and 21.4 parts of a binder.

[0076] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.6:1.

[0077] In parts by weight, the glidant consists of 0.63 parts of talc, 2.5 parts of colloidal silicon dioxide, and 0.75 parts of magnesium stearate.

[0078] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0079] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0080] The preparation method of the corn starch slurry comprises the following steps:

[0081] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0082] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0083] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0084] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0085] S3 drying, drying the furosemide granules;

[0086] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0087] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0088] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0089] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0090] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0091] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0092] The binder was added to the granulator at a temperature of 40°C.

[0093] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0094] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0095] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0096] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0097] Example 2

[0098] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 3.88 parts of a glidant, and 21.4 parts of a binder.

[0099] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.8:1.

[0100] In parts by weight, the glidant consists of 0.63 parts of talc, 2.5 parts of colloidal silicon dioxide, and 0.75 parts of magnesium stearate.

[0101] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0102] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0103] The preparation method of the corn starch slurry comprises the following steps:

[0104] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0105] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0106] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0107] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0108] S3 drying, drying the furosemide granules;

[0109] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0110] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0111] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0112] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0113] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0114] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0115] The binder was added to the granulator at a temperature of 40°C.

[0116] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0117] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0118] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0119] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0120] Example 3

[0121] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 0.63 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0122] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0123] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0124] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0125] The preparation method of the corn starch slurry comprises the following steps:

[0126] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0127] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0128] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0129] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0130] S3 drying, drying the furosemide granules;

[0131] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0132] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0133] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0134] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0135] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0136] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0137] The binder was added to the granulator at a temperature of 40°C.

[0138] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0139] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0140] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0141] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0142] Example 4

[0143] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 0.63 parts of talc, 1.25 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0144] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0145] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0146] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0147] The preparation method of the corn starch slurry comprises the following steps:

[0148] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0149] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0150] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0151] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0152] S3 drying, drying the furosemide granules;

[0153] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0154] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0155] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0156] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0157] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0158] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0159] The binder was added to the granulator at a temperature of 40°C.

[0160] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0161] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0162] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0163] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0164] Example 5

[0165] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 0.63 parts of talc, 1.88 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0166] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0167] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0168] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0169] The preparation method of the corn starch slurry comprises the following steps:

[0170] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0171] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0172] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0173] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0174] S3 drying, drying the furosemide granules;

[0175] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0176] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0177] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0178] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0179] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0180] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0181] The binder was added to the granulator at a temperature of 40°C.

[0182] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0183] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0184] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0185] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0186] Example 6

[0187] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 1.25 parts of talc, 1.88 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0188] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0189] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0190] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0191] The preparation method of the corn starch slurry comprises the following steps:

[0192] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0193] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0194] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0195] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0196] S3 drying, drying the furosemide granules;

[0197] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0198] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0199] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0200] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0201] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0202] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0203] The binder was added to the granulator at a temperature of 40°C.

[0204] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0205] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0206] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0207] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0208] Example 7

[0209] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 1.88 parts of talc, 1.88 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0210] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0211] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0212] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0213] The preparation method of the corn starch slurry comprises the following steps:

[0214] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0215] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0216] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0217] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0218] S3 drying, drying the furosemide granules;

[0219] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0220] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0221] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0222] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0223] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0224] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0225] The binder was added to the granulator at a temperature of 40°C.

[0226] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0227] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0228] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0229] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0230] Example 8

[0231] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 3.13 parts of talc, 1.88 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0232] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0233] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0234] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0235] The preparation method of the corn starch slurry comprises the following steps:

[0236] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0237] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0238] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0239] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0240] S3 drying, drying the furosemide granules;

[0241] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0242] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0243] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0244] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0245] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0246] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0247] The binder was added to the granulator at a temperature of 40°C.

[0248] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0249] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0250] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0251] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0252] Example 9

[0253] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 6.25 parts of talc, 1.88 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0254] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0255] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0256] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0257] The preparation method of the corn starch slurry comprises the following steps:

[0258] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0259] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0260] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0261] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0262] S3 drying, drying the furosemide granules;

[0263] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0264] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0265] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0266] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0267] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0268] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0269] The binder was added to the granulator at a temperature of 40°C.

[0270] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0271] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0272] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0273] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0274] Example 10

[0275] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 2.5 parts of talc, 1.88 parts of colloidal silicon dioxide, 0.38 parts of magnesium stearate, and 21.4 parts of a binder.

[0276] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0277] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0278] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0279] The preparation method of the corn starch slurry comprises the following steps:

[0280] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0281] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0282] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0283] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0284] S3 drying, drying the furosemide granules;

[0285] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0286] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0287] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0288] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0289] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0290] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0291] The binder was added to the granulator at a temperature of 40°C.

[0292] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0293] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0294] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0295] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0296] Example 11

[0297] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 2.5 parts of talc, 1.88 parts of colloidal silicon dioxide, 1.25 parts of magnesium stearate, and 21.4 parts of a binder.

[0298] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0299] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0300] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0301] The preparation method of the corn starch slurry comprises the following steps:

[0302] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0303] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0304] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0305] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0306] S3 drying, drying the furosemide granules;

[0307] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0308] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0309] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0310] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0311] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0312] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0313] The binder was added to the granulator at a temperature of 40°C.

[0314] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0315] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0316] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0317] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0318] Example 12

[0319] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 69.16 parts of a filler, 2.5 parts of talc, 1.88 parts of colloidal silicon dioxide, 2.5 parts of magnesium stearate, and 21.4 parts of a binder.

[0320] The filler consists of corn starch and anhydrous lactose, and the mass ratio of the corn starch to the anhydrous lactose is 0.65:1.

[0321] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0322] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0323] The preparation method of the corn starch slurry comprises the following steps:

[0324] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0325] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0326] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0327] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0328] S3 drying, drying the furosemide granules;

[0329] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0330] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0331] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0332] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0333] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0334] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0335] The binder was added to the granulator at a temperature of 40°C.

[0336] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0337] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0338] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0339] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0340] Example 13

[0341] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0342] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0343] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0344] The preparation method of the corn starch slurry comprises the following steps:

[0345] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0346] A second aspect of this embodiment provides a preparation process of furosemide tablets, comprising the following steps:

[0347] S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix;

[0348] S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules;

[0349] S3 drying, drying the furosemide granules;

[0350] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0351] S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules;

[0352] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0353] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0354] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0355] In S2, corn starch and anhydrous lactose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0356] The binder was added to the granulator at a temperature of 40°C.

[0357] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0358] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0359] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0360] In the step S5, the dry particles and talc are mixed and stirred at a stirring frequency of 35 Hz, with forward rotation for 30 seconds, reverse rotation for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0361] Example 14

[0362] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0363] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0364] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0365] The preparation method of the corn starch slurry comprises the following steps:

[0366] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0367] The second aspect of this embodiment provides a preparation process of furosemide tablets, and the specific implementation method is the same as that of Example 13.

[0368] Example 15

[0369] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0370] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0371] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 10%.

[0372] The preparation method of the corn starch slurry comprises the following steps:

[0373] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 10%.

[0374] The second aspect of this embodiment provides a preparation process of furosemide tablets, and the specific implementation method is the same as that of Example 13.

[0375] Example 16

[0376] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0377] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0378] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0379] The preparation method of the corn starch slurry comprises the following steps:

[0380] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0381] The second aspect of this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that the temperature of the binder when added to the granulator is 76.5°C.

[0382] Example 17

[0383] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0384] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0385] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0386] The preparation method of the corn starch slurry comprises the following steps:

[0387] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0388] The second aspect of this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that the temperature of the binder when added to the granulator is 57.0°C.

[0389] Example 18

[0390] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0391] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0392] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0393] The preparation method of the corn starch slurry comprises the following steps:

[0394] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0395] The second aspect of this embodiment provides a preparation process of furosemide tablets. The specific implementation method is the same as that of Example 13, except that the temperature of the binder when added to the granulator is 50.4°C.

[0396] Example 19

[0397] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0398] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0399] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0400] The preparation method of the corn starch slurry comprises the following steps:

[0401] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0402] The second aspect of this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that the temperature of the binder when added to the granulator is 43.8°C.

[0403] Example 20

[0404] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0405] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0406] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0407] The preparation method of the corn starch slurry comprises the following steps:

[0408] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0409] The second aspect of this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that the temperature of the binder when added to the granulator is 37°C.

[0410] Example 21

[0411] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0412] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0413] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0414] The preparation method of the corn starch slurry comprises the following steps:

[0415] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0416] In a second aspect, this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that the total mass of the binder and the mixture added is 34% of the material loading capacity of the granulator.

[0417] Example 22

[0418] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0419] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0420] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0421] The preparation method of the corn starch slurry comprises the following steps:

[0422] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0423] The second aspect of this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that the total mass of the binder and the mixture added is 52% of the material loading capacity of the granulator.

[0424] Example 23

[0425] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 21.4 parts of a binder.

[0426] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0427] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0428] The preparation method of the corn starch slurry comprises the following steps:

[0429] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0430] In a second aspect, this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that the total mass of the binder and the mixture added is 67% of the material loading capacity of the granulator.

[0431] Example 24

[0432] In a first aspect, the present embodiment provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 20.4 parts of a binder.

[0433] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0434] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0435] The preparation method of the corn starch slurry comprises the following steps:

[0436] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0437] The second aspect of this embodiment provides a preparation process of furosemide tablets, and the specific implementation method is the same as that of Example 13.

[0438] Example 25

[0439] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 22.4 parts of a binder.

[0440] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0441] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0442] The preparation method of the corn starch slurry comprises the following steps:

[0443] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0444] The second aspect of this embodiment provides a preparation process of furosemide tablets, and the specific implementation method is the same as that of Example 13.

[0445] Example 26

[0446] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 22.4 parts of a binder.

[0447] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0448] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0449] The preparation method of the corn starch slurry comprises the following steps:

[0450] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0451] A second aspect of this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that in S2, corn starch and anhydrous lactose are sequentially added to a granulator and stirred and mixed for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to mix for 90 seconds, and then the binder is added to the granulator and stirred and mixed with the mixture for 110 seconds. The cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0452] Example 27

[0453] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 22.4 parts of a binder.

[0454] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0455] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0456] The preparation method of the corn starch slurry comprises the following steps:

[0457] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0458] A second aspect of this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that in S2, corn starch and anhydrous lactose are sequentially added to a granulator and stirred and mixed for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to mix for 90 seconds, and then the binder is added to the granulator and stirred and mixed with the mixture for 130 seconds. The cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0459] Example 28

[0460] In a first aspect, the present embodiment provides a furosemide tablet. The raw materials for preparing the tablet include, by weight, 25 parts of furosemide, 29.2 parts of corn starch, 41.92 parts of anhydrous lactose, 2.5 parts of talc, 0.63 parts of colloidal silicon dioxide, 0.75 parts of magnesium stearate, and 22.4 parts of a binder.

[0461] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0462] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 8%.

[0463] The preparation method of the corn starch slurry comprises the following steps:

[0464] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 8%.

[0465] A second aspect of this embodiment provides a preparation process for furosemide tablets. The specific implementation method is the same as that of Example 13, except that in S2, corn starch and anhydrous lactose are sequentially added to a granulator and stirred and mixed for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to mix for 90 seconds, and then the binder is added to the granulator and stirred and mixed with the mixture for 150 seconds. The cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0466] Example 29

[0467] This embodiment provides a furosemide tablet and a preparation method thereof. The specific implementation method is the same as that of Example 13, except that, in S5, when the dry particles and talc are mixed and stirred, the stirring paddle frequency is 35 Hz, the paddle rotates forward for 30 seconds, reverses for 30 seconds, and then continues mixing for 15 minutes, and then magnesium stearate is added and stirred and mixed for 30 minutes.

[0468] The hardness of the furosemide tablets obtained in Examples 1 to 29 was controlled to be 3-6 kg.

[0469] A hardness of 3-6 kg indicates that the furosemide tablets can withstand a pressure of 3-6 kg without breaking or shattering.

[0470] Comparative Example 1

[0471] This comparative example provides a furosemide tablet and a preparation method thereof. The specific implementation manner is the same as that of Example 1, except that the D90 particle size of the furosemide is greater than 30 μm.

[0472] Comparative Example 2

[0473] In a first aspect, the present comparative example provides a furosemide tablet, wherein the raw materials for preparing the tablet include, by weight, 24.07 parts of furosemide, 29.69 parts of corn starch, 21.66 parts of sucrose, 19.25 parts of sodium starch glycolate, 4.81 parts of dextrin, 0.52 parts of magnesium stearate, and 21.4 parts of a binder.

[0474] The furosemide has a D90 particle size of ≤30 μm and a D50 particle size of ≤12 μm.

[0475] The adhesive is corn starch slurry, which consists of corn starch and water; the mass concentration of corn starch in the corn starch slurry is 6%.

[0476] The preparation method of the corn starch slurry comprises the following steps:

[0477] Purified water at 50° C. was added to the corn starch and stirred evenly, purified water at 92° C. was then added and stirred until transparent, and purified water was added to cool the mixture to 50° C. to obtain a corn starch slurry; the amount of purified water added was controlled to adjust the mass concentration of corn starch in the corn starch slurry to 6%.

[0478] The second aspect of this comparative example provides a preparation process of furosemide tablets, comprising the following steps:

[0479] S1 dry-mixing raw materials and excipients: furosemide and dextrin are mixed and then crushed to obtain a dry mix;

[0480] S2 granulation, adding corn starch and sucrose into a granulator and stirring, then adding the dry blend and stirring to obtain a mixture, adding the binder into the granulator and stirring to obtain furosemide granules;

[0481] S3 drying, drying the furosemide granules;

[0482] S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules;

[0483] S5: mixing the dry granules with sodium starch glycolate and magnesium stearate to obtain mixed granules;

[0484] S6 tableting: the total mixed granules are compressed into tablets by a tablet press to obtain furosemide tablets.

[0485] In the S1, furosemide and colloidal silicon dioxide were mixed at a mixing speed of 11 rpm for 10 min, and were crushed and sieved using a vacuum crusher. The sieve used was an 80-mesh sieve.

[0486] The anhydrous lactose is sieved through an 80-mesh sieve; and the sieved anhydrous lactose is mixed with corn starch.

[0487] In S2, corn starch and sucrose are sequentially added to the granulator and stirred for 20 seconds. The air compressor system is turned on, the stirring frequency of the granulator stirring paddle is set to 39.4 Hz, the dry mix is ​​added and continued to be mixed for 90 seconds, and then the adhesive is added to the granulator and stirred with the mixture for 90 seconds; the cutter frequency of the granulator is set to 40 Hz, and the granulation time is 130 seconds.

[0488] The binder was added to the granulator at a temperature of 40°C.

[0489] The total mass of the binder and the mixture added was 50% of the material loading of the granulator.

[0490] During the drying in S3, the furosemide granules are spread evenly and then dried, and the spread thickness of the furosemide granules is less than 8 cm. The drying temperature in S3 is 68° C., and the drying time is 60 min.

[0491] In S4, the furosemide granules dried in S3 are screened and sized using a 24-mesh stainless steel screen, and then dried. Drying is stopped when the moisture content of the furosemide granules is controlled to be ≤3.5%, and then screened and sized using a 30-mesh stainless steel screen to obtain dry granules.

[0492] In the step S5, the dry particles and sodium starch glycolate are mixed and stirred at a stirring frequency of 35 Hz, with the stirring blade rotating forward for 30 seconds, reversed for 30 seconds, and then continued to mix for 15 minutes. Magnesium stearate is then added and stirred and mixed for 8 minutes.

[0493] Comparative Example 3

[0494] This comparative example provides a furosemide tablet and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that sucrose is used instead of anhydrous lactose.

[0495] Comparative Example 4

[0496] This comparative example provides a furosemide tablet and a preparation method thereof. The specific implementation manner is the same as that of Example 1, except that the amount of colloidal silicon dioxide used is 0 parts.

[0497] Performance Testing

[0498] 1. Dissolution test:

[0499] Instruments and equipment: drug dissolution apparatus, UV-visible spectrophotometer, electronic balance;

[0500] Reagents: phosphate buffer (pH 5.8), methanol, furosemide reference

[0501] Phosphate buffer (pH 5.8): Dissolve 68.05 g of potassium dihydrogen phosphate and 1.44 g of sodium hydroxide in water until the solution reaches 10,000 mL. Adjust the pH to within 5.8 ± 0.05.

[0502] Operation method: Dissolution medium: phosphate buffer (pH 5.8) 900 mL, rotation speed: 50 rpm, time: 45 minutes;

[0503] Take the furosemide tablets provided in Example 1-29, and measure them according to the "Standard Operating Procedure for Dissolution and Release Assay SOP-QC42-048" (Method 2). After 45 minutes, take an appropriate amount of dissolution solution, filter, accurately measure 5 mL of the filtrate, place it in a 10 mL measuring flask, dilute to the mark with the dissolution medium, shake well, and use it as the test solution. Separately take about 22 mg of the furosemide reference substance, accurately weigh it, place it in a 100 mL measuring flask, dissolve it in methanol and dilute it to the mark, accurately measure 5 mL, place it in another 100 mL measuring flask, dilute to the mark with the dissolution medium, shake well, and use it as the reference solution. Take the reference solution and the test solution, and measure the absorbance at a wavelength of 277 nm according to the "Standard Operating Procedure for Ultraviolet Visible Spectrophotometry SOP-QC42-040". The absorbance is calculated by the external standard method based on the absorbance. The limit is 85% of the labeled amount, which should meet the requirements.

[0504] Calculation formula:

[0505] r=W 外 / A 对

[0506]

[0507] Where: A 样 —Absorbance of the test solution;

[0508] A 对 —Absorbance of reference solution;

[0509] W 外 —Weighing amount of reference substance (g);

[0510] K-reference substance content (%).

[0511] The dissolution test results of the furosemide tablets provided in Examples 1-20 and Examples 24-29 using pH 4.0 acetate buffer as the dissolution medium are shown in Table 2.

[0512] The dissolution test results of the furosemide tablets provided in Examples 13-20 and Examples 24-26 using pH 5.8 phosphate buffer as the dissolution medium are shown in Table 3.

[0513] 2. Mixing uniformity test:

[0514] The mixing uniformity of the raw materials during the preparation of the furosemide tablets provided in Examples 21-23 was tested. The test results are shown in Table 4.

[0515] The mixing uniformity test method is tested in accordance with the "Technical Guidelines for the Study of Mixing Uniformity and Unit Uniformity of Controlled Doses of Chemical Oral Solid Preparations (Trial)", of which the following test guidelines are provided on page 4: It is recommended to select at least 10 sampling points in the mixing equipment and / or intermediate material container, and take at least 3 samples at each sampling point. The sampling volume of a single sample should generally be in the range of 1-10 times the unit dose, and the entire sample should be used for mixing uniformity testing, and double sampling should be avoided. It is recommended to evaluate the impact of the powder sampling volume. When the sampling volume of a single sample is greater than 3 times the unit dose, it is necessary to demonstrate or scientifically explain it, and provide relevant evidence to ensure that the sampling volume can be used to determine the true mixing uniformity of the mixture. The following test methods are provided on page 6: (I) Acceptance criteria for mixing uniformity 1. Select at least 10 sampling points in the entire batch and take at least 3 samples from each sampling point; 2. Test one sample at each sampling point and calculate the relative standard deviation (RSD) of all samples (n≥10), with all single values ​​within ±10.0% (absolute) of the mean; (1) If RSD≤5.0%, perform the uniformity test of the in-process control dose unit; (2) If RSD>5.0%, test the mixing uniformity of the remaining samples (all untested samples at each sampling point).

[0516] 3. Disintegration time test:

[0517] Testing Method: Turn on the power and heat according to the "ZB-1D Intelligent Disintegration Apparatus Standard Operation, Maintenance, and Service Procedure (SOP-PE16-066). Check the cleanliness of the glass container and fill it with approximately 900 ml of purified water, setting the water temperature to 37°C. Six tablets from each batch of furosemide tablets prepared in Examples 1-10 and Comparative Examples 1-4 were placed in the intelligent disintegration apparatus for disintegration testing. The test results are shown in Table 5.

[0518] 4. Friability test:

[0519] Test Method: Follow the "Fragility Tester Standard Operating Procedure (SOP-PE16-058)" before testing. Adjust the instrument's speed to 25 ± 1 rpm and set the test time to 4 minutes. The tablets should be rolled a total of 100 times. Dosage of the furosemide tablets provided in Examples 1-10 and Comparative Examples 1-4: For each test, remove several tablets of the test sample and remove any powder to a total weight of approximately 6.5 g.

[0520] Inspection method: Place the weighed sample in a circular cylinder and start the motor to test. After the test, remove the sample and inspect it. The sample must not be broken, cracked, or shattered. Take the sample after the test and weigh it on a balance.

[0521] Calculation: Weigh the sample before and after the test. Calculate the weight loss after the test compared to before the test. Calculate the percentage of the weight loss to the pre-test weight. See Table 5 for test results.

[0522] Results and judgment: If no breakage, cracking or crushed pieces are detected and the weight loss does not exceed 1%, it is judged to be in compliance with the regulations. If the weight loss exceeds 1% but no breakage, cracking or crushed pieces are detected, another sample should be taken to repeat the test twice. If the average weight loss of the three tests does not exceed 1%, it is judged to be in compliance with the regulations. If the average weight loss of the three tests exceeds 1%, it is judged to be non-compliant. If the sample is broken, cracked or crushed, it is judged to be non-compliant.

[0523] 5. Hardness Test: The test was performed in accordance with Standard Operating Procedure for Hardness Tester (SOP-PE16-068). Five furosemide tablets from Examples 1-10 and Comparative Examples 1-4 were tested for hardness on any track of each tablet press. The hardness data were recorded. The test results are shown in Table 5.

[0524] 6. Flowability test: The flowability of the furosemide tablets provided in Examples 1-10 and Comparative Examples 1-4 was tested using the angle of repose method.

[0525] 7. Yield Test: The yield of the furosemide tablets provided in Examples 1-10 and Comparative Examples 1-4 was tested. The test results are shown in Table 5.

[0526]

[0527] 8. Disintegration state test:

[0528] The disintegration state of the furosemide tablets provided in Example 10-Example 12 was tested in a pH 4.0 acetate buffer as a dissolution medium. The test results are shown in Table 6.

[0529] The dissolution test results of the furosemide tablets provided in Examples 1-20 and Examples 24-29 using pH 4.0 acetate buffer as the dissolution medium are shown in Table 2.

[0530] Table 2 Dissolution in pH 4.0 acetate buffer

[0531]

[0532] It can be seen from the test data in Table 2 that when the mass concentration of corn starch in Example 1 and Example 2 is increased, the solubility is low in pH 4.0 acetate buffer as the dissolution medium; the higher the temperature of corn starch slurry addition, the more obvious the slowing of dissolution behavior in pH 4.0 acetate buffer as the dissolution medium. It is possible that the higher the temperature of corn starch slurry, the better its fluidity and the stronger the prepared particles, resulting in slower dissolution behavior. Therefore, the temperature of corn starch slurry addition is controlled not to exceed 50°C; when the amount of corn starch slurry added is 20.4-22.4 parts, the solubility is high in pH 4.0 acetate buffer as the dissolution medium, and the dissolution behavior is faster.

[0533] The dissolution test results of the furosemide tablets provided in Examples 13-20 and Examples 24-26 using pH 5.8 phosphate buffer as the dissolution medium are shown in Table 3.

[0534] Table 3 Dissolution of pH 5.8 phosphate buffer

[0535]

[0536]

[0537] The test data in Table 3 show that when the amount of corn starch slurry added in Examples 13-20 and Examples 24-26 is 20.4-22.4 parts and the mass concentration of corn starch in the corn starch slurry is 6%-8%, the obtained furosemide tablets have a high solubility in pH 5.8 phosphate buffer as the dissolution medium, and the dissolution behavior is faster.

[0538] The mixing uniformity of the raw materials during the preparation of the furosemide tablets provided in Examples 21-23 was tested. The test results are shown in Table 4.

[0539] Table 4 Mixing uniformity RSD results

[0540] DETAILED DESCRIPTION Mixing uniformity RSD value Example 21 0.92％ Example 22 0.54％ Example 23 1.32％

[0541] It can be seen from the test data in Table 4 that when the total mass of the corn starch slurry and the mixture added is 34%-67% of the material loading capacity of the granulator, the RSD values ​​obtained when the corn starch slurry and the mixture are mixed are all less than 3.0%, achieving a uniform mixing state.

[0542] The disintegration test results of the furosemide tablets provided in Example 1-10 and Comparative Example 1-4 are shown in Table 5.

[0543] Table 5 Quality inspection after tableting

[0544]

[0545]

[0546] The disintegration state of the furosemide tablets provided in Example 10-Example 12 was tested in a pH 4.0 acetate buffer as a dissolution medium. The test results are shown in Table 6.

[0547] Table 6 Disintegration state in pH 4.0 medium

[0548] Example Disintegration state in pH 4.0 medium Example 10 20-40s collapse Example 11 30-60s disintegration Example 12 60-120s disintegration

[0549] It can be seen from the test data in Table 6 that the disintegration state test of the furosemide tablets provided in Examples 10-12 shows that when the magnesium stearate reaches 2.50 parts, the disintegration time is increased and the dissolution rate is reduced.

Claims

1. A furosemide tablet, characterized in that The raw materials for its preparation include 20-25 parts of furosemide, 65-70 parts of filler, 1.6-10 parts of glidant and 20-23 parts of adhesive by weight; the glidant includes talc, colloidal silicon dioxide and magnesium stearate.

2. The furosemide tablets according to claim 1, wherein The fillers include corn starch and anhydrous lactose.

3. The furosemide tablets according to claim 2, wherein The mass ratio of the corn starch to anhydrous lactose is (0.6-0.8):

1.

4. The furosemide tablets according to claim 1, wherein The adhesive comprises corn starch slurry, which comprises corn starch and water. The mass concentration of corn starch in the corn starch slurry is 6%-8%.

5. A method for preparing the furosemide tablets according to any one of claims 1 to 4, characterized in that: The following steps are involved: S1 dry-mixing raw materials and excipients: furosemide and colloidal silicon dioxide are mixed and then pulverized to obtain a dry mix; S2 granulation, adding the filler into a granulator and stirring, then adding the dry blend and stirring and mixing to obtain a mixture, adding the binder into the granulator and stirring and mixing with the mixture, and granulating to obtain furosemide granules; S3 drying, drying the furosemide granules; S4 granulation: the furosemide granules dried in S3 are granulated using a sifter to obtain dry granules; S5: mixing the dry granules with talc and magnesium stearate to obtain mixed granules; S6 tableting: compressing the total mixed granules into tablets to obtain furosemide tablets.

6. The method for preparing furosemide tablets according to claim 5, wherein: The stirring speed of the adhesive and the mixture in S2 is 250-350 rpm, and the stirring time is 60-200 s.

7. The method for preparing furosemide tablets according to claim 5, wherein: The temperature of the binder added to the granulator is less than 50°C.

8. The method for preparing furosemide tablets according to claim 5, wherein: The stirring speed used in the granulation in S2 is 260 rpm-300 rpm, and the granulation time is 140 s-180 s.

9. The method for preparing furosemide tablets according to claim 5, wherein: The granulation in S4 is performed using a 30-mesh stainless steel sieve.

10. The method for preparing furosemide tablets according to claim 5, wherein: In S5, the dry particles and talc are mixed and stirred at a rotation speed of 35 Hz, a forward rotation time of 30 s, and a reverse rotation time of 30 s. The mixing is continued for 15 min, and magnesium stearate is then added and stirred and mixed for 8-30 min.

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