Indobufen pharmaceutical composition and preparation method thereof

Abstract

The invention discloses an indobufen pharmaceutical composition and a preparation method thereof, and relates to the technical field of medicine preparation. The indobufen pharmaceutical composition is prepared from the following raw materials and auxiliary materials in parts by weight: 36-40 parts of indobufen, 36-40 parts of lactose, 14-18 parts of microcrystalline cellulose, 4-6 parts of carboxymethyl starch sodium, 1-1.5 parts of magnesium dodecyl sulfate and 1.5-2 parts of magnesium stearate, the distribution of particles with the particle size of 75 microns or less is not less than 88%, and the bulk density is 0.50-0.55 g / cm < 3 >. According to the indobufen pharmaceutical composition, by controlling the density and particle size distribution of indobufen particles, the indobufen particles have large particle size distribution, the distribution of large particles with the particle size larger than 250 microns is not lower than 55%, the distribution of fine powder with the particle size smaller than 125 microns is not higher than 30%, the indobufen pharmaceutical composition has a large proportion of coarse particles to fine powder, a chromium nitride plated stamping die is adopted for tabletting, sticking is avoided in the tabletting process, and the indobufen pharmaceutical composition is suitable for large-scale production. The prepared tablet is smooth and beautiful, and the particle size distribution of the carboxymethyl starch sodium has obvious influence on the dissolution stability of the tablet.

Description

Technical Field

[0001] The invention relates to the technical field of drug preparation, in particular to an indobufen drug composition and a preparation method thereof. Background Art

[0002] Indobufen, English name: Indobufen, chemical name: (±) 2-[4-(1-oxo-2-isoindole) phenyl] butyric acid, CAS: 63610-08-2, molecular formula C18H17NO3, indobufen (K3920) was developed as a new platelet aggregation inhibitor in 1980. It can inhibit the release of platelet factors such as ADP, 5-hydroxytryptamine, platelet factor 4, β-thromboglobulin, etc., and play an anti-platelet aggregation role. It does not affect the plasma parameters of blood coagulation, but only prolongs the bleeding time. Therefore, after achieving the therapeutic purpose, stopping the drug can quickly recover and restore abnormal platelet function to normal. On May 5, 1984, Pfizer's indobufen tablets were approved for marketing in Italy under the trade name Ibustrin, with a specification of 200mg, for the prevention of coronary artery bypass vascular occlusion and the treatment of intermittent claudication caused by peripheral arterial occlusive disease.

[0003] Indobufen is a white crystalline powder with high viscosity. The dosage form is relatively large at 200 mg. The API accounts for a large proportion of the dosage form. There is a serious sticking problem during tableting, which poses a great challenge to industrial production. In addition, research has shown that the original preparation Ibustrin has a significantly reduced dissolution problem during accelerated testing, which has an adverse effect on the quality of the product.

[0004] Chinese patent CN114681444A discloses an indobufen pharmaceutical composition, which increases the bulk density and tap density of the powder by adding sodium dodecyl sulfate or magnesium dodecyl sulfate, which is beneficial to improving fluidity, and controls the particle size of indobufen below 100 meshes, thereby increasing the solubility of the product to 95.8%. However, the solubility of the composition still needs to be improved.

[0005] In summary, the preparation of indobufen tablets in the prior art has the following problems: first, there is a sticking problem in the tableting process; second, there is a problem of reduced dissolution during the stability test process, which affects the quality of the sample. Third, the solubility of indobufen needs to be further improved. Therefore, the present invention improves and optimizes the formulation process to solve the above problems of indobufen tablets. Summary of the invention

[0006] In view of the deficiencies in the prior art, the present invention solves the problems of sticking in the tableting process of indobufen tablets, the problem of reduced dissolution during stability investigation and the problem that the solubility of indobufen needs to be further improved in the prior art. The present invention provides an indobufen pharmaceutical composition with simple preparation process, good stability and high solubility and a preparation method thereof.

[0007] To achieve the above objectives, the present invention is implemented by the following technical scheme: an indobufen pharmaceutical composition, comprising the following raw materials and auxiliary materials by weight: 36-40 parts of indobufen, 36-40 parts of lactose, 14-18 parts of microcrystalline cellulose, 4-6 parts of sodium carboxymethyl starch, 1-1.5 parts of lauryl magnesium sulfate, and 1.5-2 parts of magnesium stearate;

[0008] The sodium carboxymethyl starch has the characteristics of fine particle size distribution and low bulk density, the distribution of particles below 75 um is not less than 88%, and the bulk density is 0.50-0.55 g / cm3.

[0009] The second aspect of the present invention provides a method for preparing an indobufen pharmaceutical composition, comprising the following preparation steps:

[0010] Step S1, premixing: adding indobufen, lactose, microcrystalline cellulose, sodium starch glycolate and magnesium lauryl sulfate into an improved wet granulator and mixing to obtain indobufen tablet premix powder.

[0011] Step S2, wet granulation: granulation is performed using purified water as a wetting agent. After the spraying is completed, the obtained granules are wet granulated using a swing granulator with a 16-20 mesh sieve.

[0012] Step S3, dry granulation: fluidized bed drying, the obtained granules are dry granulated using a mobile granulator with a 1.5-2.0 mm screen to obtain indobufen tablet granules.

[0013] Step S4, total mixing and tableting: the indobufen particles and magnesium stearate are uniformly mixed to obtain a total mixed powder, and then tableted.

[0014] Preferably, the wet granulator comprises:

[0015] A frame, used to provide a foundation for the wet granulator as a whole;

[0016] A mixing unit, arranged on the frame and used to ensure that the materials are fully mixed;

[0017] A premixing unit, disposed above the mixing unit and used for premixing the added raw materials;

[0018] A conveying unit, disposed below the mixing unit and used for conveying the mixed materials;

[0019] A granulating unit, which is arranged at the rear end of the conveying unit and is used to granulate the conveyed material;

[0020] The driving unit is arranged at the rear end of the granulating unit and is used to drive the mixing unit, the premixing unit, the conveying unit and the granulating unit to be in a synchronous operation state.

[0021] Preferably, the mixing unit comprises:

[0022] A mixing box is arranged above the frame;

[0023] A mixing and stirring blade is arranged inside the mixing box;

[0024] The second discharge pipe is arranged at the discharge position of the mixing box, and a second solenoid valve is arranged on the second discharge pipe.

[0025] Preferably, the premixing unit comprises:

[0026] A premixing box is arranged above the mixing box, and a nozzle is provided on the premixing box;

[0027] A first feed pipe is arranged between the premixing box and the mixing box, and a first solenoid valve is arranged on the first feed pipe;

[0028] A feed hopper, arranged on the premixing box;

[0029] The premixing stirring rod is arranged inside the premixing box.

[0030] Preferably, the transmission unit comprises:

[0031] A conveying cylinder, arranged on the second feeding pipe;

[0032] The spiral rod is arranged inside the conveying cylinder.

[0033] Preferably, the granulation unit comprises:

[0034] A granulation box is arranged on the conveying cylinder;

[0035] A sieve plate is arranged inside the granulation box;

[0036] The cutter is arranged outside the granulating box.

[0037] Preferably, the driving unit comprises:

[0038] A motor bracket is arranged on the granulation box;

[0039] A driving motor is arranged on the motor bracket;

[0040] A horizontal shaft, arranged at the output end of the driving motor, a first bevel gear is arranged on the horizontal shaft, and the cutter and the spiral rod are fixedly connected to the horizontal shaft;

[0041] A vertical shaft is arranged inside the mixing box and the premixing box, the premixing stirring rod and the mixing stirring blades are fixedly connected to the vertical shaft, and a second bevel gear is arranged on the vertical shaft, and the second bevel gear is meshed with the first bevel gear.

[0042] Preferably, a transmission box is provided on the frame, and the transmission box is used to provide protection for the transmission position of the second bevel gear and the first bevel gear, and a lubrication unit is provided on the transmission box.

[0043] Preferably, the lubrication unit comprises:

[0044] An oil tank is arranged on the side of the transmission box, and a mounting seat for supporting the oil tank is provided on the frame;

[0045] A lubrication nozzle is arranged on the oil tank, and an oil hole is opened inside the lubrication nozzle;

[0046] The guide wheel is arranged on the lubrication nozzle and fits with the oil hole position, and the guide wheel fits with the second bevel gear.

[0047] The present invention discloses an indobufen pharmaceutical composition and a preparation method thereof, which has the following beneficial effects:

[0048] 1. The indobufen pharmaceutical composition controls the density and particle size distribution of indobufen particles so that the indobufen particles have a larger particle size distribution, the distribution of large particles above 250 um is not less than 55%, and the distribution of fine powder below 125 um is not higher than 30%, so that the indobufen particles have a larger ratio of coarse particles to fine powder, and a chromium nitride plated punch is used for tableting, the tableting process does not stick to the punch, and the prepared tablet surface is smooth and beautiful. The particle size distribution of sodium carboxymethyl starch has a significant effect on the dissolution stability of the product. When sodium carboxymethyl starch has a finer particle size distribution and a lower bulk density, the distribution of particles below 75 um is not less than 88%, and the bulk density is 0.50-0.55 g / cm3, the prepared tablet has good dissolution properties and good dissolution stability, and the dissolution does not decrease during the stability study, thereby ensuring the quality stability of the product.

[0049] 2. During the preparation process of the indobufen pharmaceutical composition, the wet granulator is improved by adding a premix before the mixing process to ensure that the materials are mixed more fully and improve the preparation effect of the indobufen pharmaceutical composition. At the same time, through the design of the frame, mixing unit, premixing unit, conveying unit, granulating unit and driving unit, the driving unit is used to synchronously drive the mixing unit, premixing unit, conveying unit and granulating unit to operate. The equipment is stable and reliable during operation, and the material processing process is stable, thereby ensuring the quality stability of the product and meeting the use requirements.

[0050] 3. The indobufen pharmaceutical composition is further provided with a lubrication unit in the wet granulator, so that the transmission position of the second bevel gear and the first bevel gear is safe and reliable. At the same time, the lubrication unit reduces the resistance of the transmission position of the second bevel gear and the first bevel gear, thereby improving the stability of the system and ensuring that the production process of the indobufen pharmaceutical composition is stable and reliable, and the product quality is stable. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0052] Figure 1 Schematic diagram of the dissolution curves at day 0 of the original formulation, examples and comparative examples of the present invention;

[0053] Figure 2 Schematic diagram of accelerated 3-month dissolution curves of the original preparation of the present invention, examples and comparative examples;

[0054] Figure 3 It is a structural schematic diagram of the wet granulator of the present invention;

[0055] Figure 4 is a cross-sectional view of the wet granulator of the present invention;

[0056] Figure 5 For the present invention Figure 4 A magnified view of the structure of part A;

[0057] Figure 6 is a schematic diagram of a nozzle of the present invention;

[0058] Figure 7 It is a schematic diagram of disassembling the horizontal axis and the vertical axis of the present invention;

[0059] Figure 8 It is a structural schematic diagram of the sieve plate of the present invention;

[0060] Fig. 9It is a structural schematic diagram of the lubrication unit of the present invention;

[0061] Fig.10 It is a cross-sectional view of the lubrication unit of the present invention.

[0062] In the figure: 1, frame; 2, mixing unit; 21, mixing box; 22, mixing and stirring blades; 23, second feed pipe; 231, second solenoid valve; 3, premixing unit; 31, premixing box; 311, nozzle; 32, first feed pipe; 321, first solenoid valve; 33, feed hopper; 34, premixing stirring rod; 4, conveying unit; 41, conveying cylinder; 42, screw rod; 5, granulating unit; 51, granulating box; 52, sieve plate; 53, cutter; 6, driving unit; 61, motor bracket; 62, driving motor; 63, horizontal axis; 631, first bevel gear; 64, vertical axis; 641, second bevel gear; 7, transmission box; 8, lubrication unit; 81, oil tank; 82, lubrication nozzle; 821, oil hole; 83, guide wheel; 9, mounting seat. DETAILED DESCRIPTION

[0063] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are clearly and completely described. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0064] The embodiments of the present application provide an indobufen pharmaceutical composition and a preparation method thereof, thereby solving the problems of sticking in the tableting process of indobufen tablets, the problem of reduced dissolution during stability investigation, and the problem that the solubility of indobufen needs to be further improved in the prior art. The present invention provides an indobufen pharmaceutical composition with simple preparation process, good stability and high solubility, and a preparation method thereof.

[0065] In order to better understand the above technical solution, the above technical solution will be described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0066] Embodiment 1:

[0067] The embodiment of the present invention discloses an indobufen pharmaceutical composition, according to the attached Figure 1 To Attachment Fig.10 As shown, the following raw materials and auxiliary materials are included by weight: 36-40 parts of indobufen, 36-40 parts of lactose, 14-18 parts of microcrystalline cellulose, 4-6 parts of sodium starch glycolate, 1-1.5 parts of lauryl magnesium sulfate, and 1.5-2 parts of magnesium stearate;

[0068] Among them, sodium carboxymethyl starch has the characteristics of fine particle size distribution and low bulk density. The distribution of particles below 75um is not less than 88%, and the bulk density is 0.50-0.55g / cm3.

[0069] Indobufen particles have a large particle size distribution, with large particles above 250um being no less than 55% and fine powders below 125um being no more than 30%.

[0070] A tablet containing indobufen, with a formulation composition and mass percentage of 1000 tablets as shown in Table 1:

[0071] Table 1

[0072] Dosage g Proportion% Indobufen 200 38.50 lactose 200 38.50 Microcrystalline Cellulose 81 15.50 Sodium starch glycolate 26 5.00 Magnesium Lauryl Sulfate 5.2 1.00 Magnesium Stearate 7.8 1.50 total 520 100.00

[0073] The preparation method is as follows:

[0074] Step S1, premixing: adding indobufen, lactose, microcrystalline cellulose, sodium starch glycolate and magnesium lauryl sulfate into an improved wet granulator and mixing to obtain indobufen tablet premix powder.

[0075] Step S2, wet granulation: granulation is performed using purified water as a wetting agent. After the spraying is completed, the obtained granules are wet granulated using a swing granulator with a 16-mesh screen.

[0076] Step S3, dry granulation: fluidized bed drying, the obtained granules are dry granulated using a mobile granulator with a 1.5 mm screen to obtain indobufen tablet granules.

[0077] Step S4, total mixing and tableting: the indobufen particles and magnesium stearate are uniformly mixed to obtain a total mixed powder, and then tableted.

[0078] Furthermore, the tableting process uses a chromium nitride plated die.

[0079] Among them, the particle size distribution of sodium carboxymethyl starch is: 91.7% of particles below 75um, and the bulk density is 0.52g / cm3.

[0080] Embodiment 2:

[0081] The formula composition and mass percentage are shown in Table 2:

[0082] Table 2

[0083] Dosage g Proportion% Indobufen 200 38.50 lactose 200 38.50 Microcrystalline Cellulose 78.4 15.00 Sodium starch glycolate 26 5.00 Magnesium Lauryl Sulfate 5.2 1.00 Magnesium Stearate 10.4 2.00 total 520 100.00

[0084] The particle size distribution of sodium carboxymethyl starch is as follows: 88.7% of particles are below 75 um, and the bulk density is 0.55 g / cm3.

[0085] The material properties and preparation process are the same as those in Example 1.

[0086] Comparative Example 1

[0087] The formula composition and mass percentage are shown in Table 3:

[0088] Table 3

[0089]

[0090]

[0091] The particle size distribution of sodium carboxymethyl starch is: 76.5% of particles are below 75 μm, and the bulk density is 0.73 g / cm3. The properties of other auxiliary materials and the preparation process are the same as those in Example 1.

[0092] Comparative Example 2

[0093] The formula composition and mass percentage are shown in Table 4:

[0094] Table 4

[0095] Dosage g Proportion% Indobufen 200 38.50 lactose 200 38.50 Microcrystalline Cellulose 81 15.50 Sodium starch glycolate 26 5.00 Magnesium Lauryl Sulfate 5.2 1.00 Magnesium Stearate 7.8 1.50 total 520 100.00

[0096] The particle size distribution of sodium carboxymethyl starch is: 87.5% of particles are below 75 μm, and the bulk density is 0.68 g / cm3. The properties of other auxiliary materials and the preparation process are the same as those in Example 1.

[0097] Comparative Example 3

[0098] The formula composition and mass percentage are shown in Table 5:

[0099] Table 5

[0100]

[0101]

[0102] The material properties are the same as in Example 1.

[0103] Step S1, premixing: adding indobufen, lactose, microcrystalline cellulose, sodium starch glycolate and magnesium lauryl sulfate into an improved wet granulator and mixing to obtain indobufen tablet premix powder.

[0104] Step S2, wet granulation: granulation is performed using purified water as a wetting agent. After the spraying is completed, the obtained granules are wet granulated using a swing granulator with a 24-mesh screen.

[0105] Step S3, dry granulation: fluidized bed drying, the obtained granules are dry granulated using a mobile granulator with a 1.0 mm screen to obtain indobufen tablet granules.

[0106] Step S4, total mixing and tableting: the indobufen particles and magnesium stearate are uniformly mixed to obtain a total mixed powder, and then tableted.

[0107] Comparative Example 4

[0108] The formula composition and mass percentage are shown in Table 6:

[0109] Table 6

[0110]

[0111]

[0112] The material properties are the same as in Example 1.

[0113] The preparation method is as follows:

[0114] Step S1, premixing: adding indobufen, lactose, microcrystalline cellulose, sodium starch glycolate and magnesium lauryl sulfate into an improved wet granulator and mixing to obtain indobufen tablet premix powder.

[0115] Step S2, wet granulation: granulation is performed using purified water as a wetting agent. After the spraying is completed, the obtained granules are wet granulated using a swing granulator with a 16-mesh screen.

[0116] Step S3, dry granulation: fluidized bed drying, the obtained granules are dry granulated using a mobile granulator with a 1.5 mm screen to obtain indobufen tablet granules.

[0117] Step S4, total mixing and tableting: the indobufen particles and magnesium stearate are uniformly mixed to obtain a total mixed powder, and then tableted.

[0118] The present invention conducted a comparative experiment on the effects of the various embodiments and comparative examples on whether the tablets were sticky or not and the appearance of the tablets. The experimental results are shown in Table 7.

[0119] Table 7 Comparison of indobufen granule size and tableting results in each embodiment and comparative example

[0120]

[0121]

[0122] From the results of the tableting experiment, it can be seen that the indobufen granules in Comparative Example 3 have more fine powder and smaller particle size, and the tableting has the problem of sticking; the indobufen granules in Comparative Example 4 have larger particle size and moderate particles, but the non-chromium nitride-plated punch is used in the tableting process, and the tableting also has the problem of sticking. Since the indobufen raw material has high viscosity and the proportion of raw materials in the preparation is relatively high, it is necessary to control the particle size distribution of indobufen particles and use a chromium nitride-plated punch to ensure that the tableting process of this product does not stick.

[0123] The present invention conducted a comparative experiment on tablet dissolution stability of each embodiment and comparative example, selected pH 6.8 phosphate buffer as the dissolution medium, the medium volume was 1000 ml, the first basket method was adopted, the rotation speed was 100 rpm, and the dissolution rate was measured at 5, 10, 15, 30, 45, and 60 min. The accelerated test conditions were temperature 40°C ± 2°C and relative humidity 75% ± 5%. The experimental results are shown in Table 8.

[0124] Table 8 Comparison of dissolution stability results between examples and comparative examples

[0125]

[0126] It can be seen from the results of the dissolution stability test that the particle size distribution of sodium carboxymethyl starch used in Examples 1 and 2 is: 91.7% of particles below 75 um, and the bulk density is 0.52 g / cm3. The accelerated dissolution of the sample for 3 months is relatively stable. The proportion of particles below 75 um of sodium carboxymethyl starch used in Comparative Examples 1 and 2 is reduced, the bulk density of the particles is increased, and the accelerated dissolution in 3 months is significantly reduced. It can be seen that the particle size distribution of sodium carboxymethyl starch has a significant effect on the dissolution stability of this product. Selecting a suitable particle size distribution of sodium carboxymethyl starch can improve the dissolution stability of the preparation, which is beneficial to the stability of product quality.

[0127] Embodiment 3:

[0128] The second aspect of the present invention provides a method for preparing an indobufen pharmaceutical composition, comprising the following preparation steps:

[0129] Step S1, premixing: adding indobufen, lactose, microcrystalline cellulose, sodium starch glycolate and magnesium lauryl sulfate into an improved wet granulator and mixing to obtain indobufen tablet premix powder.

[0130] Step S2, wet granulation: granulation is performed using purified water as a wetting agent. After the spraying is completed, the obtained granules are wet granulated using a swing granulator with a 16-20 mesh sieve.

[0131] Step S3, dry granulation: fluidized bed drying, the obtained granules are dry granulated using a mobile granulator with a 1.5-2.0 mm screen to obtain indobufen tablet granules.

[0132] Step S4, total mixing and tableting: the indobufen particles and magnesium stearate are uniformly mixed to obtain a total mixed powder, and then tableted.

[0133] The wet granulator comprises a frame 1, a mixing unit 2, a premixing unit 3, a conveying unit 4, a granulating unit 5 and a driving unit 6;

[0134] The frame 1 is used to provide a foundation for the wet granulator as a whole; the frame 1 ensures that the entire wet granulator is stable under stress;

[0135] The mixing unit 2 is arranged on the frame 1 and is used to ensure that the materials are fully mixed; the premixing unit 3 is arranged above the mixing unit 2 and is used to premix the added raw materials; the device is designed so that the materials are premixed together before mixing, thereby improving the material mixing effect;

[0136] The conveying unit 4 is arranged below the mixing unit 2 and is used to convey the mixed material; the granulating unit 5 is arranged at the rear end of the conveying unit 4 and is used to granulate the conveyed material; the device facilitates the conveying of the mixed material to the granulating unit 5 through the design of the conveying unit 4, provides pressure to extrude the material and granulate it;

[0137] The driving unit 6 is arranged at the rear end of the granulating unit 5 and is used to drive the mixing unit 2, the premixing unit 3, the conveying unit 4 and the granulating unit 5 to be in a synchronous operation state. Through the design of the driving unit 6, the mixing unit 2, the premixing unit 3, the conveying unit 4 and the granulating unit 5 have a compact structure and stable transmission, thereby improving the service life of the device.

[0138] The mixing unit 2 comprises:

[0139] The mixing box 21 is arranged above the frame 1; the mixing box 21 is used to mix the premixed materials;

[0140] The mixing blade 22 is disposed inside the mixing box 21, and the mixing blade 22 is used to mix the material;

[0141] The second discharge pipe 23 is arranged at the discharge position of the mixing box 21. A second solenoid valve 231 is provided on the second discharge pipe 23. The second discharge pipe 23 is used to transfer the mixed logistics to the conveying unit 4. The design of the second solenoid valve 231 facilitates the control of the opening and closing of the channel of the second discharge pipe 23.

[0142] The premixing unit 3 comprises:

[0143] The premixing box 31 is arranged above the mixing box 21. A nozzle 311 is arranged on the premixing box 31. The premixing box 31 is used to preliminarily mix the materials to ensure a good subsequent mixing effect of the materials. The nozzle 311 is arranged to spray water, thereby facilitating the control of the humidity of the materials during the premixing process.

[0144] The first feed pipe 32 is disposed between the premixing box 31 and the mixing box 21. The first feed pipe 32 is provided with a first solenoid valve 321. The first feed pipe 32 is used to transfer the material in the premixing box 31 to the inside of the mixing box 21. The first solenoid valve 321 is used to control the opening and closing of the channel of the first feed pipe 32.

[0145] The feed hopper 33 is arranged on the premixing box 31. The design of the feed hopper 33 facilitates the addition of raw materials into the premixing box 31.

[0146] The premixing stirring rod 34 is disposed inside the premixing box 31 . The design of the premixing stirring rod 34 facilitates the addition of raw materials into the premixing box 31 .

[0147] The transmission unit 4 comprises:

[0148] The conveying cylinder 41 is arranged on the second feeding tube 23;

[0149] The screw rod 42 is disposed inside the conveying cylinder 41 . The conveying unit 4 has a simple structure, and the material is pushed by the rotation of the screw rod 42 inside the conveying cylinder 41 .

[0150] The granulation unit 5 comprises:

[0151] The granulation box 51 is arranged on the conveying cylinder 41; the granulation box 51 is used to guide the material;

[0152] The sieve plate 52 is arranged inside the granulation box 51; when the material is transported to the inside of the granulation box 51 through the conveying unit 4 and contacts the sieve plate 52, the thrust exerted on the material will push the material through the sieve plate 52 and squeeze outward, thereby forming a strip shape;

[0153] The cutter 53 is arranged outside the granulating box 51. When the cutter 53 rotates continuously, the cutter 53 cuts the strip material squeezed out of the sieve plate 52 into granules.

[0154] The drive unit 6 comprises:

[0155] The motor bracket 61 is arranged on the granulation box 51;

[0156] A driving motor 62 is disposed on the motor bracket 61;

[0157] A horizontal shaft 63 is provided at the output end of the driving motor 62. A first bevel gear 631 is provided on the horizontal shaft 63. The cutter 53 and the spiral rod 42 are fixedly connected to the horizontal shaft 63.

[0158] A vertical shaft 64 is disposed inside the mixing box 21 and the premixing box 31. The premixing stirring rod 34 and the mixing stirring blade 22 are fixedly connected to the vertical shaft 64. A second bevel gear 641 is disposed on the vertical shaft 64. The second bevel gear 641 is meshed with the first bevel gear 631.

[0159] The driving unit 6 has a compact structure. Through the design of the driving unit 6, it is easy to realize the synchronous movement of the mixing unit 2, the premixing unit 3, the conveying unit 4 and the granulating unit 5;

[0160] The driving unit 6 is powered by a driving motor 62, which drives the horizontal shaft 63 to rotate, and the horizontal shaft 63 drives the cutter 53, the spiral rod 42 and the first bevel gear 631 to rotate; the first bevel gear 631 drives the second bevel gear 641 to rotate, and the second bevel gear 641 drives the vertical shaft 64 to rotate, and the vertical shaft 64 drives the mixing and stirring blades 22 and the premixing and stirring rod 34 to rotate.

[0161] A transmission box 7 is provided on the frame 1, and the transmission box 7 is used to provide protection for the transmission position of the second bevel gear 641 and the first bevel gear 631. A lubrication unit 8 is provided on the transmission box 7, and the transmission box 7 makes the transmission position of the second bevel gear 641 and the first bevel gear 631 safe and reliable. At the same time, the lubrication unit 8 makes the transmission position resistance of the second bevel gear 641 and the first bevel gear 631 small, thereby improving the stability of the system.

[0162] The lubrication unit 8 comprises:

[0163] The oil tank 81 is arranged on the side of the transmission box 7, and the frame 1 is provided with a mounting seat 9 for supporting the oil tank 81;

[0164] A lubrication nozzle 82 is disposed on the oil tank 81, and an oil hole 821 is provided inside the lubrication nozzle 82;

[0165] The guide wheel 83 is disposed on the lubrication nozzle 82 and is in close contact with the oil hole 821 . The guide wheel 83 is in close contact with the second bevel gear 641 .

[0166] The lubrication unit 8 has a compact structure and is easy to use. The lubricating oil is stored in the oil tank 81. The lubricating oil is continuously provided to the surface of the guide wheel 83 through the design of the lubrication nozzle 82 and the oil hole 821. When the second bevel gear 641 rotates, it will drive the guide wheel 83 to rotate, and then the guide wheel 83 transfers the lubricating oil adhered to it to the second bevel gear 641, and then transfers it to the first bevel gear 631 through the second bevel gear 641, so that the first bevel gear 631 and the second bevel gear 641 do not need special lubrication, and the transmission position resistance is small.

[0167] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the existence of other identical elements in the process, method, article or device including the elements.

[0168] The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. It should be understood by those skilled in the art that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention to be protected. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. An indobufen pharmaceutical composition, characterized in that: The following raw materials and auxiliary materials are included by weight: 36-40 parts of indobufen, 36-40 parts of lactose, 14-18 parts of microcrystalline cellulose, 4-6 parts of sodium starch glycolate, 1-1.5 parts of lauryl magnesium sulfate, and 1.5-2 parts of magnesium stearate; The sodium carboxymethyl starch has the characteristics of fine particle size distribution and low bulk density, the distribution of particles below 75 um is not less than 88%, and the bulk density is 0.50-0.55 g / cm3.

2. The method for preparing an indobufen pharmaceutical composition according to claim 1, characterized in that: The method comprises the following preparation steps: Step S1, premixing: adding indobufen, lactose, microcrystalline cellulose, sodium starch glycolate, and magnesium lauryl sulfate into an improved wet granulator and mixing to obtain indobufen tablet premix powder; Step S2, wet granulation: granulation is performed using purified water as a wetting agent. After the spraying is completed, the obtained granules are wet granulated using a swing granulator with a 16-20 mesh sieve; Step S3, dry granulation: fluidized bed drying, using a mobile granulator to dry granulate the obtained granules using a 1.5-2.0 mm screen to obtain indobufen tablet granules; Step S4, total mixing and tableting: the indobufen particles and magnesium stearate are uniformly mixed to obtain a total mixed powder, and then tableted.

3. The method for preparing an indobufen pharmaceutical composition according to claim 2, characterized in that: The wet granulator comprises: A frame (1) for providing a foundation for the wet granulator as a whole; A mixing unit (2) is arranged on the frame (1) and is used to ensure that the materials are fully mixed; A premixing unit (3), arranged above the mixing unit (2) and used for premixing the added raw materials; A conveying unit (4) is arranged below the mixing unit (2) and is used to convey the mixed materials; A granulating unit (5) is arranged at the rear end of the conveying unit (4) and is used to granulate the conveyed material; The driving unit (6) is arranged at the rear end of the granulating unit (5) and is used to drive the mixing unit (2), the premixing unit (3), the conveying unit (4) and the granulating unit (5) to be in a synchronous operation state.

4. The method for preparing an indobufen pharmaceutical composition according to claim 3, characterized in that: The mixing unit (2) comprises: A mixing box (21) is arranged above the frame (1); A mixing and stirring blade (22) is arranged inside the mixing box (21); The second material discharge pipe (23) is arranged at the material discharge position of the mixing box (21), and a second solenoid valve (231) is provided on the second material discharge pipe (23).

5. The method for preparing an indobufen pharmaceutical composition according to claim 4, characterized in that: The premixing unit (3) comprises: A premixing box (31) is disposed above the mixing box (21), and a nozzle (311) is provided on the premixing box (31); A first feed pipe (32) is disposed between the premixing box (31) and the mixing box (21), and a first solenoid valve (321) is provided on the first feed pipe (32); A feed hopper (33) is arranged on the premixing box (31); The premixing stirring rod (34) is arranged inside the premixing box (31).

6. The method for preparing an indobufen pharmaceutical composition according to claim 5, characterized in that: The transmission unit (4) comprises: A conveying cylinder (41) is arranged on the second feeding pipe (23); The spiral rod (42) is arranged inside the conveying cylinder (41).

7. The method for preparing an indobufen pharmaceutical composition according to claim 6, characterized in that: The granulation unit (5) comprises: A granulation box (51) is arranged on the conveying cylinder (41); A sieve plate (52) is arranged inside the granulation box (51); The cutter (53) is arranged outside the granulation box (51).

8. The method for preparing an indobufen pharmaceutical composition according to claim 7, characterized in that: The driving unit (6) comprises: A motor support (61) is arranged on the granulation box (51); A driving motor (62) is arranged on the motor bracket (61); A transverse shaft (63) is arranged at the output end of the driving motor (62), a first bevel gear (631) is arranged on the transverse shaft (63), and the cutter (53) and the spiral rod (42) are fixedly connected to the transverse shaft (63); A vertical shaft (64) is disposed inside the mixing box (21) and the premixing box (31); the premixing stirring rod (34) and the mixing stirring blade (22) are fixedly connected to the vertical shaft (64); a second bevel gear (641) is provided on the vertical shaft (64); and the second bevel gear (641) is meshed with the first bevel gear (631).

9. The method for preparing an indobufen pharmaceutical composition according to claim 8, characterized in that: A transmission box (7) is provided on the frame (1), the transmission box (7) is used to provide protection for the transmission position of the second bevel gear (641) and the first bevel gear (631), and a lubrication unit (8) is provided on the transmission box (7).

10. The method for preparing an indobufen pharmaceutical composition according to claim 9, characterized in that: The lubrication unit (8) comprises: An oil tank (81) is arranged on a side of the transmission box (7), and a mounting seat (9) for supporting the oil tank (81) is provided on the frame (1); A lubrication nozzle (82) is arranged on the oil tank (81), and an oil hole (821) is provided inside the lubrication nozzle (82); The guide wheel (83) is arranged on the lubrication nozzle (82) and is in close contact with the oil hole (821); the guide wheel (83) is in close contact with the second bevel gear (641).

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