Albendazole dispersible tablet and preparation method thereof

Abstract

The invention discloses a preparation method of an albendazole dispersible tablet. The albendazole dispersible tablet is prepared from the following components in parts by weight: 4 parts of albendazole, 2 to 3 parts of a disintegrating agent, 1.2 to 1.8 parts of a filling agent, 0.2 to 0.3 part of a flavoring agent, 0.08 to 0.1 part of a flow aid A, 0.03 to 0.08 part of a flow aid B and 0.2 to 0.3 part of an adhesive. The preparation method of the dispersible tablet comprises the following steps: S1, weighing the filler, the disintegrating agent, the albendazole, the flavoring agent, the flow aid A and the flow aid B, grinding, sieving and drying for later use; dissolving an adhesive in water for later use; s2, wet granulation; s3, after granulation is finished, sieving and drying are performed, and whole granules are sieved, so that whole dry granules are obtained; and S4, totally mixing, tabletting and packaging. According to the invention, high-speed granulation, multi-stage drying and colloidal silicon dioxide modification processes are combined, so that medicine particles are more uniform and fine, the dispersibility is high, the preparation process is simple, the equipment demand is low, the dissolution amount is high, the bioavailability is improved, and the treatment effect is enhanced.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and particularly relates to an albendazole dispersible tablet and a preparation method thereof. Background Art

[0002] Albendazole is a broad-spectrum anti-parasitic drug, belonging to the derivatives of benzimidazoles. It can selectively and irreversibly inhibit the polymerization of the cytoplasmic microtubule system of intestinal parasites and intestinal wall cells, block the uptake and absorption of various nutrients and glucose, cause endogenous sugar depletion in the worms, and can inhibit the fumarate reductase system, prevent the production of adenosine triphosphate, resulting in the inability of the worms to survive and reproduce. It is widely used in the treatment of various parasitic infections. Traditional albendazole tablets have problems such as slow dissolution rate and low bioavailability, which affect their efficacy. In order to improve the dissolution rate and bioavailability of albendazole, researchers have developed albendazole dispersible tablets. However, traditional albendazole tablets still have problems. The dissolution rate is slow. Albendazole has poor water solubility, resulting in a slow dissolution rate in the gastrointestinal tract, affecting drug absorption and bioavailability. Due to poor solubility, the bioavailability of traditional tablets is relatively low, and a higher dose is required to achieve the therapeutic effect. The stability is poor. Traditional tablets are prone to moisture absorption and caking during storage, affecting the stability and efficacy of the drug.

[0003] In the prior art, there are already some preparation methods for albendazole dispersible tablets, but these methods have problems such as complex processes, high costs, and insufficient stability. Although the solubility has been improved, the problems of stability and bioavailability have not been solved, or complex coating technologies and the addition of special excipients are used, increasing the production cost. Therefore, it is of important practical significance to develop an albendazole dispersible tablet with simple process, low cost, fast dissolution rate, good stability and high bioavailability. Summary of the Invention

[0004] In view of the above deficiencies, the present invention provides an albendazole dispersible tablet and a preparation method thereof, which have the advantages of fast dissolution rate, high bioavailability and good stability. The preparation process is simple, the required equipment is less, and the cost is low. The specific technical solutions are as follows:

[0005] A preparation method of an albendazole dispersible tablet, characterized in that the albendazole dispersible tablet comprises, by weight: 4 parts of albendazole, 2 - 3 parts of disintegrant, 1.2 - 1.8 parts of filler, 0.2 - 0.3 parts of flavoring agent, 0.08 - 0.1 part of glidant A, 0.03 - 0.08 part of glidant B, and 0.2 - 0.3 part of binder.

[0006] The preparation method of the albendazole dispersible tablet comprises the following steps:

[0007] S1. Weigh the filler, disintegrant, albendazole, flavoring agent, glidant A, and glidant B, respectively put them into a grinder for grinding, then pass through a 1.2 mm sieve, dry and reserve; Divide the sieved and dried filler and disintegrant into two equal parts respectively, one part as the internal added material and one part as the external added material, reserve; Slowly add the binder to a certain amount of hot purified water while stirring until dissolved to obtain a binder solution, reserve;

[0008] S2. Put the filler as the internal added material, the disintegrant as the internal added material, and the sieved and dried albendazole described in step S1 into a wet granulator, add the binder solution described in step S1 under low-speed granulation conditions, start high-speed granulation for 7 - 12 min after low-speed granulation for 2 - 3 min;

[0009] S3. After granulation, pass through a 5.0×5.0 mm sieve, then carry out drying treatment, end drying when the drying loss rate ≤ 2.5%, and carry out sieving and sizing after drying to obtain the sized dry granules;

[0010] S4. Put the sized dry granules described in step S3, the filler as the external added material, the disintegrant as the external added material, the flavoring agent, and glidant A into a hopper, mix evenly, then add glidant B and mix. After mixing, carry out tabletting and packaging to obtain the albendazole dispersible tablets.

[0011] Preferably, the disintegrant is crospovidone.

[0012] Preferably, the filler is microcrystalline cellulose.

[0013] Preferably, the flavoring agent is selected from one or more of orange flavor essence and saccharin sodium.

[0014] Preferably, the glidant A is modified colloidal silica and the glidant B is magnesium stearate.

[0015] Preferably, the binder is selected from one or more of povidone K30 and Tween - 80.

[0016] Preferably, in step S2, the stirring paddle speed in low-speed granulation is 80 - 100 r / min, and the granulation knife rotation speed is 950 - 1050 r / min; The stirring paddle speed in high-speed granulation is 80 - 100 r / min, and the granulation knife rotation speed is 1400 - 1600 r / min.

[0017] Preferably, the specific steps of the drying treatment are: Set the air inlet volume of the fluidized bed dryer to 2500 - 3000 m 3 / h, the inlet air temperature to 85 - 95 °C, the end temperature to 50 - 60 °C, stop heating after drying for 4 - 6 min, and continue to set the air inlet volume of the fluidized bed dryer to 4000 - 5000 m 3 / h, inlet air temperature is 55 - 65°C, final temperature is 30 - 45°C, drying lasts for 10 - 15 min, start the bag shaking, detect the loss on drying of the granules until it is ≤ 2.5%, and end the drying.

[0018] Preferably, the preparation method of the modified colloidal silica comprises the following steps: Dissolve polylactic acid in ethanol to prepare a 2% - 5% polylactic acid solution, mix colloidal silica and the polylactic acid solution evenly according to the mass ratio of 1 - 2:10, heat and stir at 60 - 70°C for 3 - 5 hours, wash with ethanol after the reaction ends, and dry to obtain the modified colloidal silica.

[0019] The present invention provides an albendazole dispersible tablet prepared by the above preparation method.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] 1. The method of wet granulation of albendazole in the present invention makes the drug granules more uniform and delicate, significantly improves the dispersibility, has a simple preparation process and requires less equipment. The use of the disintegrant cross-linked povidone further accelerates the disintegration speed of the tablets in vivo, ensures that the drug can be rapidly released and dissolved, thereby improving the bioavailability and enhancing the therapeutic effect. The combination of polysorbate 80, povidone K30 and magnesium stearate improves the wettability of albendazole, makes the drug dissolve faster, ensures the mechanical strength of the tablets during the tabletting process, and avoids tablet fragmentation. The division of the present invention into internal feeding and external feeding helps to improve the rapid disintegration and dissolution of the drug, improve the dissolution rate, improve the fluidity of the granules, make the tabletting step smoother, and the tablet weight more stable.

[0022] 2. During the preparation process of the present invention, by controlling the stirring paddle speed and the rotating speed of the granulating knife for low-speed and high-speed granulation, the uniformity and compactness of the granules are ensured. The segmented temperature control technology is adopted during the drying process, which avoids over-drying of the granules or residual moisture, shortens the production cycle, improves the granule quality, avoids surface hardening of the granules and residual internal moisture, and ensures the uniformity and stability of the granules.

[0023] 3. Through the surfactant modification of colloidal silica in the present invention, the dispersibility and wettability of colloidal silica are improved, the granulation process is more stable, the phenomenon of particle sticking to the wall is reduced, the dispersibility and stability of colloidal silica can be significantly improved, and thus the bioavailability of the drug is improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for description in the embodiments. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without creative efforts.

[0025] Figure 1 This is the dissolution test chart of product S230503l obtained in Example 1 of the present invention and the original research chewable tablet 9J8E of Comparative Example 3. Specific embodiments

[0026] The following is a detailed description of the specific embodiments of the present invention, but it should be understood that the protection scope of the present invention is not limited by the specific embodiments. Unless otherwise defined, all professional terms used hereinafter have the same meaning as commonly understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the protection scope of the present invention. Unless otherwise specifically stated, all kinds of raw materials, reagents, instruments and equipment used in the present invention can be obtained through market purchase or can be prepared by existing methods.

[0027] Example 1

[0028] The albendazole dispersible tablets in this example include, by weight: 4 parts of albendazole, 2 parts of crospovidone, 1.2 parts of microcrystalline cellulose, 0.2 part of orange flavor essence, 0.08 part of modified colloidal silica, 0.03 part of magnesium stearate, 0.2 part of povidone K30, and 0.1 part of tween-80.

[0029] The albendazole dispersible tablets in this example specifically include the following steps:

[0030] 1. Premixing. Weigh the raw materials according to the above ratios; put albendazole, crospovidone, microcrystalline cellulose, orange flavor essence, modified colloidal silica, and magnesium stearate into a grinder for grinding respectively, then pass through a 1.2 mm sieve, dry and reserve; divide the dried microcrystalline cellulose and crospovidone into two equal parts respectively, one part as the internal added material and one part as the external added material, reserve; slowly add povidone K30 to 5 times the mass of hot purified water of povidone K30 while stirring, stir until dissolved to obtain a povidone K30 solution, slowly add tween-80 to 5 times the mass of hot purified water of tween-80 while stirring, stir until dissolved to obtain a tween-80 solution, reserve.

[0031] The preparation method of the modified colloidal silica includes the following steps: dissolve polylactic acid in ethanol to prepare a 2% polylactic acid solution, mix colloidal silica and the polylactic acid solution evenly according to a mass ratio of 1:10, heat and stir at 60 °C for 3 hours, wash with ethanol after the reaction, and dry to obtain the modified colloidal silica.

[0032] 2. Granulation. Add microcrystalline cellulose as internal additive, crospovidone as internal additive, and albendazole after sieving and drying into a wet granulator. Set the stirring paddle speed to 90 r / min and the granulation knife speed to 1000 r / min. Add the povidone K30 solution and Tween-80 solution described in step 1, and granulate at low speed for 2 min. Set the stirring paddle speed in high-speed granulation to 90 r / min and the granulation knife speed to 1500 r / min, and granulate at high speed for 10 min. After discharging, screen the granules through a 5.0×5.0 mm sieve and transfer them to a started fluidized bed dryer.

[0033] 3. Drying. Set the air inlet volume of the fluidized bed dryer to 2500 m 3 / h, the inlet air temperature to 85 °C, the end temperature to 50 °C, stop heating after drying for 5 min, and continue to set the air inlet volume of the fluidized bed dryer to 4000 m 3 / h, the inlet air temperature to 55 °C, the end temperature to 30 °C, dry for 10 min, turn on the bag shaking function, detect the loss on drying of the granules until ≤2.5%, end drying, and discharge and screen the granules after continuous bag shaking.

[0034] 4. Screening. Screen the dried granules through a 0.8 mm sieve (rotation speed 600 r / min), and the screened granules enter the hopper to obtain the screened dry granules.

[0035] 5. Total mixing. Add the screened dry granules, microcrystalline cellulose as external additive, crospovidone as external additive, saccharin sodium, orange flavor essence, and modified colloidal silica into the hopper. Set the mixing speed of the mixer to 8 r / min and the mixing time to 20 min, then add magnesium stearate, set the mixing speed of the mixer to 8 r / min and the mixing time to 5 min. After mixing, store the granules for standby.

[0036] 6. Tabletting. Use a special-shaped punch die of Φ=18.0 mm*8.5 mm to tablet the granules in step 5. Feed the granules into the hopper from the upper feed inlet of the tablet press. Set the feeder speed of the tablet press to 50 rpm, the standard pressure to 25 KN, and the tabletting speed to 60 thousand tablets per hour. Debug the tablet press according to the theoretical tablet weight of 0.8500 g / tablet. After tabletting, take samples and weigh the unit tablet weight to be controlled within ±5% (0.8075 g~0.8925 g). The sampled tablets are detected for thickness at 7.6 mm, hardness at 11 kg, and the dispersion uniformity is that all tablets disintegrate within 3 min and pass through a 710 μm sieve, the disintegration time limit is 2.5 min, and the friability is 0.8%. After passing the inspection (thickness 7 - 8 mm, hardness 8 - 16 kg, disintegration time limit < 3 min, friability < 1% is considered qualified), tablet the tablets, and package the pressed plain tablets to obtain the product.

[0037] Example 2

[0038] This albendazole dispersible tablets in this example, by weight, include: 4 parts of albendazole, 3 parts of crospovidone, 1.8 parts of microcrystalline cellulose, 0.3 parts of orange flavor essence, 0.1 parts of modified colloidal silica, 0.08 parts of magnesium stearate, and 0.2 parts of povidone K30.

[0039] The preparation method of this albendazole dispersible tablets in this example specifically includes the following steps:

[0040] 1. Premixing. Weigh the raw materials according to the above ratio; put albendazole, crospovidone, microcrystalline cellulose, orange flavor essence, modified colloidal silica, and magnesium stearate into a grinder for grinding respectively, then pass through a 1.2 mm sieve, dry and reserve; divide the dried microcrystalline cellulose and crospovidone into two equal parts respectively, one part as the internal added material and one part as the external added material, reserve; slowly add povidone K30 to 5 times the mass of hot purified water of povidone K30 while stirring, and stir until dissolved to obtain a povidone K30 solution, reserve.

[0041] The preparation method of modified colloidal silica includes the following steps: dissolve polylactic acid in ethanol to prepare a 5% polylactic acid solution, mix colloidal silica and polylactic acid solution evenly according to a mass ratio of 2:10, heat and stir at 70 °C for 5 hours, wash with ethanol after the reaction ends, and dry to obtain modified colloidal silica.

[0042] 2. Granulation. Add the microcrystalline cellulose as the internal added material, the crospovidone as the internal added material, and the sieved and dried albendazole into a wet granulator, set the stirring paddle speed at 100 r / min and the granulating knife speed at 1050 r / min, add the povidone K30 solution described in step 1, and granulate at low speed for 2 min. Set the stirring paddle speed in high-speed granulation at 90 r / min and the granulating knife speed at 1500 r / min, granulate at high speed for 10 min, and after discharging, screen through a 5.0×5.0 mm sieve and transfer to a started fluidized bed dryer.

[0043] 3. Drying. Set the air inlet volume of the fluidized bed dryer at 3000 m 3 / h, the inlet air temperature at 95 °C, the end temperature at 60 °C, stop heating after drying for 5 min, continue to set the air inlet volume of the fluidized bed dryer at 5000 m 3 / h, the inlet air temperature at 65 °C, the end temperature at 45 °C, dry for 15 min, turn on the shaking bag, detect the loss on drying of the particles until ≤2.5%, end drying, and discharge and screen after continuous shaking bagging.

[0044] 4. Screening. Screen the dried particles through a 0.8 mm sieve (rotation speed 600 r / min), and the screened particles enter the hopper to obtain the screened dry particles.

[0045] 5. Total mixing. Add the granulated dry granules, microcrystalline cellulose as an external additive, crospovidone as an external additive, sodium saccharin, orange flavor essence, and modified colloidal silica into the hopper. Set the mixing speed of the mixer at 8 r / min and the mixing time at 20 min. Then add magnesium stearate, set the mixing speed of the mixer at 8 r / min and the mixing time at 5 min. After mixing, store the granules for standby.

[0046] 6. Tabletting. Use a special-shaped punch die with Φ = 18.0 mm * 8.5 mm to tablet the granules obtained in step 5. Feed the granules into the hopper from the upper feed inlet of the tabletting machine. Set the feeding speed of the tabletting machine feeder at 50 rpm, the standard pressure at 25 KN, and the tabletting speed at 60 thousand tablets per hour. Debug the tabletting machine according to the theoretical tablet weight of 0.8500 g / tablet. After tabletting, take samples and weigh the unit tablet weight to be controlled within ±5% (0.8075 g - 0.8925 g). Test the thickness of the sampled tablets to be 7.5 mm, the hardness to be 13 kg, the dispersion uniformity to be completely disintegrated within 3 min and pass through a 710 μm sieve, the disintegration time limit to be 2.5 min, and the friability to be 0.8%. After passing the tests (the thickness is 7 - 8 mm, the hardness is 8 - 16 kg, the disintegration time limit is < 3 min, and the friability is < 1% for passing the tests), tablet the tablets. Package the pressed plain tablets to obtain the product.

[0047] Example 3

[0048] The albendazole dispersible tablets in this example include, by weight: 4 parts of albendazole, 2 parts of crospovidone, 1.8 parts of microcrystalline cellulose, 0.2 parts of orange flavor essence, 0.1 parts of modified colloidal silica, 0.08 parts of magnesium stearate, and 0.2 parts of Tween - 80.

[0049] The albendazole dispersible tablets in this example specifically include the following steps:

[0050] 1. Premixing. Weigh the raw materials according to the above ratio; put microcrystalline cellulose, crospovidone, orange flavor essence, modified colloidal silica, and magnesium stearate into the grinder for grinding respectively, and then pass through a 1.2 mm sieve. After drying, store them for standby; divide the dried microcrystalline cellulose and crospovidone into two equal parts respectively, one part as the internal additive and one part as the external additive, and store them for standby; slowly add Tween - 80 to 5 times the mass of hot purified water while stirring until it is dissolved to obtain a Tween - 80 solution for standby.

[0051] The preparation method of the modified colloidal silica includes the following steps: Dissolve polylactic acid in ethanol to prepare a 3% polylactic acid solution. Mix colloidal silica and the polylactic acid solution evenly according to a mass ratio of 1.5:10, heat and stir at 65 °C for 4 hours. After the reaction, wash with ethanol and dry to obtain the modified colloidal silica.

[0052] 2. Granulation. Add microcrystalline cellulose as the internal additive, crospovidone as the internal additive, and albendazole after sieving and drying into a wet granulator. Set the stirring paddle speed to 80 r / min and the granulation knife speed to 950 r / min. Add the Tween-80 solution described in step 1 and granulate at low speed for 2 min. Set the stirring paddle speed in high-speed granulation to 90 r / min and the granulation knife speed to 1500 r / min. Granulate at high speed for 10 min. After discharging, screen the granules through a 5.0×5.0 mm sieve and transfer them to a started fluidized bed dryer.

[0053] 3. Drying. Set the air intake of the fluidized bed dryer to 2800 m 3 / h, the inlet air temperature to 90 °C, the end temperature to 55 °C, stop heating after drying for 5 min, and continue to set the air intake of the fluidized bed dryer to 4500 m 3 / h, the inlet air temperature to 60 °C, the end temperature to 40 °C, dry for 12 min, turn on the bag shaking function, detect the loss on drying of the granules until ≤2.5%, end the drying, and discharge the granules after continuous bag shaking for screening.

[0054] 4. Screening. Screen the dried granules through a 0.8 mm sieve (rotation speed 600 r / min), and the screened granules enter the hopper to obtain the screened dry granules.

[0055] 5. Total mixing. Add the screened dry granules, microcrystalline cellulose as the external additive, crospovidone as the external additive, saccharin sodium, orange flavor essence, and modified colloidal silica to the hopper. Set the mixing speed of the mixer to 8 r / min and the mixing time to 20 min. Then add magnesium stearate, set the mixing speed of the mixer to 8 r / min and the mixing time to 5 min. After mixing, store the granules for standby.

[0056] 6. Tabletting. Use a special-shaped punch die of Φ = 18.0 mm * 8.5 mm to tablet the granules in step 5. Feed the granules into the hopper from the upper feed inlet of the tablet press. Set the feeder speed of the tablet press to 30 rpm, the standard pressure to 20 KN, and the tabletting speed to 50 thousand tablets per hour. Debug the tablet press according to the theoretical tablet weight of 0.8500 g / tablet. After tabletting, take samples and weigh the unit tablet weight to be controlled within ±5% (0.8075 g - 0.8925 g). Take samples of the tablets to detect the thickness at 7.4 mm, the hardness at 12 kg, the dispersion uniformity to be completely disintegrated within 3 min and pass through a 710 μm sieve, the disintegration time limit to be 2.4 min, and the friability to be 0.8%. After passing the inspection (thickness 7 - 8 mm, hardness 8 - 16 kg, disintegration time limit < 3 min, friability < 1% is considered qualified), tablet the tablets, and package the produced plain tablets to obtain the product.

[0057] Comparative Example 1

[0058] The difference from Example 1 is that the colloidal silica is not modified.

[0059] Comparative Example 2

[0060] The difference from Example 1 lies in the drying operation, as follows: Set the air intake of the fluidized bed dryer to 2500 m 3 / h, the inlet air temperature to 85 °C, the end temperature to 50 °C, stop heating, continue to blow cold until the discharge temperature reaches 30 °C, turn on the vibrating bag, detect the loss on drying of the granules until it is ≤ 2.5%, and end the drying.

[0061] Comparative Example 3

[0062] This comparative example is the original research chewable tablet 9J8E produced by GlaxoSmithKline (GSK).

[0063] 1. Dissolution test

[0064] Name the product obtained in Example 1 as S230503l, and conduct a dissolution test with the original research chewable tablet 9J8E of Comparative Example 3. Take 6 dispersible tablets for each group, according to the paddle method of the dissolution test method, use 900 mL of 0.1 mol / L hydrochloric acid as the dissolution medium, the rotation speed is 50 r / min. After 30 min, take 10 mL of the solution and filter it through a filter membrane. Take 5 mL of the filtrate and place it in a 250 mL volumetric flask, dilute it to the mark with 0.1 mol / L sodium hydroxide solution, and shake well. Determine according to the ultraviolet-visible spectrophotometry method. Measure the absorbance at the wavelengths of 308 nm and 350 nm respectively, calculate the dissolution of a single tablet, and take the average value as the dissolution of the test sample. The results are as Figure 1 .

[0065] 2. Pharmacokinetic test

[0066] Take 40 healthy male mice, 5 weeks old, with a body weight of 20 - 30 g. Administer the albendazole dispersible tablet suspension prepared in Example 1 and Comparative Examples 1 - 3 to 10 mice in each group by gavage. Fast for 12 h before administration, allow free access to water, and the dosage is 50 mg / kg. Take blood samples to detect the albendazole content at 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, and 36 h after administration respectively. Centrifuge at 4 °C and 12000 rpm for 10 min to separate the plasma, obtain the plasma sample. Take 100 μL of the plasma sample, add 30 μL of 1 μg / mL mebendazole internal standard solution and mix, then add 600 μL of methanol, mix well for 3 min to precipitate proteins, centrifuge at 10000 r / min for 10 min, aspirate the supernatant, and determine the plasma drug concentration. The results are shown in Table 1 below.

[0067] Table 1

[0068]

[0069]

[0070] As can be seen from the above table, the dispersible tablets of the present invention can reach the effective blood drug concentration in a relatively short time, the maximum blood drug concentration is significantly increased, and the maintenance time of the effective blood pressure concentration in the body is longer, indicating that the dispersible tablets prepared by the present invention effectively improve the oral bioavailability of the drug in the body.

[0071] In summary, the method of wet granulation of albendazole in the present invention makes the drug particles more uniform and delicate, and the dispersibility is significantly improved. The preparation process is simple and the equipment requirements are small. The use of the disintegrant crospovidone further accelerates the disintegration speed of the tablets in the body, ensuring that the drug can be rapidly released and dissolved, thereby improving the bioavailability and enhancing the therapeutic effect. The combination of polysorbate 80, povidone K30 and magnesium stearate improves the wettability of albendazole, enables the drug to dissolve faster, ensures the mechanical strength of the tablets during the tabletting process, and avoids tablet fragmentation. The present invention is divided into internal feeding and external feeding, which helps to improve the rapid disintegration and dissolution of the drug, improve the dissolution rate, improve the particle fluidity, make the tabletting step smoother and the tablet weight more stable. During the preparation process of the present invention, by controlling the stirring paddle speed and the granulating knife speed of low-speed and high-speed granulation, the uniformity and compactness of the particles are ensured. During the drying process, the segmented temperature control technology is adopted to avoid over-drying of the particles or moisture residue, shorten the production cycle, improve the particle quality, avoid surface hardening of the particles and internal moisture residue, and ensure the uniformity and stability of the particles. Through the surfactant modification of colloidal silica in the present invention, the dispersibility and wettability of colloidal silica are improved, the granulation process is more stable, the phenomenon of particle sticking to the wall is reduced, the dispersibility and stability of colloidal silica can be significantly improved, and thus the bioavailability of the drug is improved.

[0072] The foregoing description of specific exemplary embodiments of the invention has been presented for purposes of illustration and example. These descriptions are not intended to limit the invention to the precise forms disclosed, and it is apparent that, according to the above teachings, many modifications and variations are possible. The purpose of selecting and describing the exemplary embodiments is to explain the specific principles of the invention and its practical applications, so that those skilled in the art can implement and utilize the various different exemplary embodiments of the invention, as well as various different selections and modifications. The scope of the invention is intended to be defined by the claims and their equivalents.

Claims

1. A method for preparing albendazole dispersible tablets, characterized in that: The albendazole dispersible tablets include, by weight: 4 parts of albendazole, 2-3 parts of disintegrant, 1.2-1.8 parts of filler, 0.2-0.3 parts of flavoring agent, 0.08-0.1 parts of glidant A, 0.03-0.08 parts of glidant B, and 0.2-0.3 parts of binder; The preparation method of the albendazole dispersible tablets comprises the following steps: S1. Weigh filler, disintegrant, albendazole, flavoring agent, glidant A and glidant B, grind them respectively, sieve them, dry them and set them aside; divide the sieved and dried filler and disintegrant into two equal parts, one of which is used as internal additive and the other as external additive for later use; slowly add binder to a certain amount of hot purified water while stirring, stir until dissolved, and obtain binder solution for later use; S2, adding the filler as internal additive, the disintegrant as internal additive, and the sieved and dried albendazole described in step S1 into a wet granulator, adding the binder solution described in step S1 under low-speed granulation conditions, and starting high-speed granulation for 7-12 minutes after low-speed granulation for 2-3 minutes; S3, after granulation, sieve and dry. When the drying loss is ≤2.5%, the drying is completed. After drying, sieve and granulate to obtain dry granules. S4, adding the dry granules after granulation in step S3 and the filler as an external material, the disintegrant as an external material, the flavoring agent, and the glidant A into a hopper and mixing them evenly, then adding the glidant B and mixing, and after mixing, tableting and packaging are performed to obtain the albendazole dispersible tablets.

2. The method for preparing a dispersible albendazole tablet according to claim 1, wherein: The disintegrant is cross-linked polyvinylpyrrolidone.

3. The method for preparing a dispersible albendazole tablet according to claim 1, wherein: The filler is microcrystalline cellulose.

4. The method for preparing a dispersible albendazole tablet according to claim 1, wherein: The flavoring agent is selected from one or more of orange flavor and saccharin sodium.

5. The method for preparing a dispersible albendazole tablet according to claim 1, wherein: The glidant A is modified colloidal silicon dioxide, and the glidant B is magnesium stearate.

6. The method for preparing a dispersible albendazole tablet according to claim 1, wherein: The adhesive is selected from one or more of povidone K30 and Tween-80.

7. The method for preparing a dispersible albendazole tablet according to claim 1, wherein: In step S2, the stirring paddle speed in the low-speed granulation is 80-100 r / min, and the granulating knife speed is 950-1050 r / min; the stirring paddle speed in the high-speed granulation is 80-100 r / min, and the granulating knife speed is 1400-1600 r / min.

8. The method for preparing a dispersible albendazole tablet according to claim 1, wherein: The specific steps of the drying process are as follows: setting the air volume of the boiling dryer to 2500-3000m 3 / h, air inlet temperature 85-95℃, end point temperature 50-60℃, stop heating after drying for 4-6 minutes, and continue to set the air inlet volume of the boiling dryer to 4000-5000m 3 / h, air inlet temperature 55-65℃, end point temperature 30-45℃, drying for 10-15min, and the drying weight loss of the particles is detected to be ≤2.5%, then the drying is finished.

9. The method for preparing a dispersible albendazole tablet according to claim 1, wherein: The preparation method of the modified colloidal silica comprises the following steps: dissolving polylactic acid in ethanol to prepare a 2%-5% polylactic acid solution, uniformly mixing the colloidal silica and the polylactic acid solution at a mass ratio of 1-2:10, heating and stirring at 60-70° C. for 3-5 hours, washing with ethanol after the reaction is completed, and drying to obtain the modified colloidal silica.

10. An albendazole dispersible tablet, characterized in that: The dispersible tablet is prepared by the preparation method according to any one of claims 1 to 9.

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