Tamsulosin hydrochloride sustained-release capsule and preparation method thereof

Abstract

The invention relates to the field of pharmaceutical preparations, and discloses a tamsulosin hydrochloride sustained-release capsule and a preparation method thereof.The sustained-release capsule is prepared from, by mass, 0.1%-0.2% of tamsulosin hydrochloride, 5%-20% of sustained-release framework material and 80%-95% of filler, the sustained-release framework material is methacrylic acid-ethyl acrylate copolymer, and the filler is a filler. The filling agent comprises starch and microcrystalline cellulose; the dissolution behavior of the sustained-release capsule is consistent with that of an original development agent; the starch in the sustained-release capsule can remarkably reduce the dosage of the methacrylic acid-ethyl acrylate copolymer, and the production cost is remarkably reduced while the weight and the sustained-release effect of the sustained-release capsule are not changed; according to the preparation method of the tamsulosin hydrochloride sustained-release capsule, water with the water temperature being greater than or equal to 50 DEG C is selected as a solvent of tamsulosin hydrochloride, so that the pill preparation yield is remarkably improved, the production efficiency is remarkably improved, and the pill uniformity is remarkably improved.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, in particular to a tamsulosin hydrochloride sustained-release capsule and a preparation method thereof. Background Art

[0002] Tamsulosin hydrochloride is a novel α1 receptor blocker that selectively blocks α1 receptors in the smooth muscle of the bladder neck, prostate gland, and prostate capsule, reducing smooth muscle tone and lower urinary tract resistance, thereby improving urinary dysfunction caused by benign prostatic hyperplasia (BPH). It can be used to treat abnormal urination symptoms associated with BPH, such as frequent urination, increased nocturia, and dysuria. It achieves its therapeutic goal by improving smooth muscle function in the urethra, bladder neck, and prostate, rather than shrinking the prostatic hyperplasia. Therefore, it is suitable for patients with mild to moderate BPH and those without severe urinary dysfunction.

[0003] Tamsulosin hydrochloride sustained-release capsule oral preparation was first developed by a Japanese company as an original formulation for the treatment of symptoms of benign prostatic hyperplasia. When adults take a single oral dose of 0.2 mg, the blood concentration reaches its peak after 6.8 hours, the half-life reaches 10 hours, and the drug absorption is low when taken on an empty stomach or after eating. This preparation suffers from problems such as slow absorption, long time to peak blood concentration, and susceptibility to dietary influences. Therefore, to improve the above-mentioned problems, a variety of tamsulosin hydrochloride preparations have been developed in the prior art, such as the tamsulosin hydrochloride sustained-release preparation and preparation method disclosed in publication number CN108096220B. This method applies a double-layer tamsulosin hydrochloride sustained-release coating to a microcrystalline cellulose pellet core to form sustained-release micropellets. This preparation has a sustained-release effect at pH 1 to 6.8, which solves the effect of gastrointestinal pH changes after eating on the absorption of tamsulosin hydrochloride.

[0004] In addition, the solubility of tamsulosin hydrochloride in water at 37°C is 0.5g / L, which is relatively low in solubility. Therefore, the prior art generally adopts an equivalent incremental method to improve the mixing effect, but the production process of this method is complicated and dust-producing, and the yield is low and low-cost. Therefore, in order to improve the above problems, the prior art uses an organic solvent to dissolve tamsulosin hydrochloride. For example, publication number CN102106841B discloses a tamsulosin hydrochloride preparation and a preparation method thereof, in which methanol is used as a solvent. Although the use of an organic solvent can solve the problem caused by the low solubility of tamsulosin hydrochloride, the use of an organic solvent still has the problem that the organic solvent is volatile and easy to remain. Therefore, when using an organic solvent agent, it is necessary to have conditions such as an explosion-proof workshop and organic solvent residual quality control, and the production cost is still relatively high. Therefore, in order to further reduce production costs, it is necessary to further optimize the preparation method of tamsulosin hydrochloride. Summary of the Invention

[0005] The present invention provides a tamsulosin hydrochloride sustained-release capsule. The dissolution behavior of the sustained-release capsule is consistent with that of the original formulation. The production cost of the sustained-release capsule is significantly reduced by adjusting the composition of the sustained-release material.

[0006] The present invention also provides a method for preparing tamsulosin hydrochloride sustained-release capsules. The method uses water as a solvent for tamsulosin hydrochloride, significantly improving the solubility of tamsulosin hydrochloride by controlling the water temperature. At the same time, the content uniformity of the pills prepared by the method is significantly improved, with a standard deviation of less than 1%.

[0007] The specific technical solutions of the present invention are: A tamsulosin hydrochloride sustained-release capsule comprises the following components by mass percentage: 0.1-0.2% tamsulosin hydrochloride, 5-20% sustained-release matrix material, wherein the sustained-release matrix material is methacrylic acid-ethyl acrylate copolymer; and 80-95% filler, wherein the filler comprises starch and microcrystalline cellulose.

[0008] Preferably, the methacrylic acid-ethyl acrylate copolymer is one of Eudragit L30D-55 and Eudragit L100-55.

[0009] Preferably, the sustained-release material further comprises a plasticizer and an anti-adhesive agent.

[0010] Preferably, the plasticizer is one or both of triethyl citrate and PEG400.

[0011] Preferably, the anti-sticking agent is talc.

[0012] The present invention finds that by adding starch to the formulation of pharmaceutical pills, the dosage of methacrylic acid-ethyl acrylate copolymer and plasticizer can be significantly reduced without changing the dissolution effect and weight of the sustained-release capsules, thereby significantly reducing production costs.

[0013] A method for preparing the above-mentioned tamsulosin hydrochloride sustained-release capsules comprises the following steps: (1) The filler and the anti-adhesive agent are mixed evenly, and then the tamsulosin hydrochloride solution is added, and then the methacrylic acid-ethyl acrylate copolymer and the plasticizer are added to prepare a soft material, and the soft material is made into pills; the temperature of the water used for preparing the tamsulosin hydrochloride solution is 50-70°C, (2) Methacrylic acid-ethyl acrylate is dispersed in water and a plasticizer and an anti-sticking agent are added to prepare a coating solution, and the pills are coated with the coating solution to prepare tamsulosin hydrochloride sustained-release capsules.

[0014] Preferably, the soft material is made by a wet mixing granulation device, and the conditions of the wet mixing granulation device are: a stirring speed of 100 to 150 r / min, a cutting speed of 1000 to 1500 r / min, Preferably, the soft material is extruded and spheronized into pharmaceutical pills using an extrusion and spheronization integrated machine with the following parameters: extrusion screen 0.8-1.0 mm, spheronization parameter 400-600 rpm, time 100-200 s.

[0015] Preferably, the particle size of the pills is 16 to 45 meshes.

[0016] Preferably, the coating process adopts fluidized bed bottom spray coating method.

[0017] Preferably, the coating treatment conditions are: the material temperature during coating is 25-35°C, and the curing temperature is 40-50°C.

[0018] Preferably, the coating weight gain is 2.5-4.5% of the pill mass.

[0019] The present invention also provides a method for preparing the aforementioned tamsulosin hydrochloride sustained-release capsules. Tamsulosin hydrochloride typically has a low solubility in water at room temperature. The Japanese Pharmacopoeia indicates that the solubility of tamsulosin hydrochloride in water at 37°C is only above 0.5 g / L. This low solubility results in a low yield of pills per batch during actual processing. However, the present invention finds that the solubility of tamsulosin hydrochloride significantly increases in water at temperatures above 50°C, reaching a solubility of above 20 g / L. Therefore, the present invention selects water with a temperature of ≥50°C as the solvent for tamsulosin hydrochloride. This method significantly improves the yield of pill preparation and production efficiency. Furthermore, the method improves the uniformity of the pills, with the uniformity of the tamsulosin hydrochloride content in a batch of pills being less than 1.0%.

[0020] Compared with the existing technology, this application has the following technical effects: (1) The sustained-release materials in the tamsulosin hydrochloride sustained-release capsules are methacrylic acid-ethyl acrylate copolymer and plasticizer methacrylic acid-ethyl acrylate copolymer. Starch can significantly reduce the amount of methacrylic acid-ethyl acrylate copolymer and plasticizer, thereby significantly reducing production costs without changing the weight of the sustained-release capsules and the sustained-release effect; (2) In the preparation method of the tamsulosin hydrochloride sustained-release capsules, water with a water temperature of ≥50°C is selected as the solvent for tamsulosin hydrochloride, which significantly improves the yield of pill preparation, significantly improves production efficiency, and significantly improves the uniformity of pills. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 The solubility curve of tamsulosin hydrochloride in water is 37.5-90°C.

[0022] Figure 2 The dissolution curves of Examples 1 to 7 and Comparative Examples 1 to 3 in standard medium are shown.

[0023] Figure 3 The dissolution curves of Example 1 and Comparative Example 3 at pH 4.0 for 24 hours are shown.

[0024] Figure 4 The dissolution curves of Example 1 and Comparative Example 3 at pH 6.8 for 8 h are shown. DETAILED DESCRIPTION

[0025] The present invention will be further described below with reference to the embodiments.

[0026] In order to better understand the content of the present invention, the following is further described in conjunction with specific examples. It should be understood that the following examples are only used to illustrate the present invention and are not used to limit the scope of the present invention.

[0027] Example 1: A tamsulosin hydrochloride sustained-release capsule, the composition of each capsule is shown in the following table: A method for preparing the above-mentioned tamsulosin hydrochloride sustained-release capsules comprises the following steps: (1) Add 100 g of water to a stainless steel barrel and heat to 50°C. Then add 2 g of tamsulosin hydrochloride and stir until completely dissolved at a stirring speed of 120 r / min. (2) Add 1104 g of microcrystalline cellulose, 276 g of starch, and 98 g of anti-sticking agent to a wet mixer and stir until uniformly mixed. Stir and mix until uniformly mixed. The stirring speed is 100 r / min and the shear speed is 1200 r / min. Then add tamsulosin hydrochloride solution for 1 to 3 minutes. (3) 100 g of methacrylic acid-ethyl acrylate copolymer and 10 g of plasticizer were added to 1 L of water and mixed uniformly to prepare a polymer solution. The polymer solution was added to a wet mixer and stirred and sheared to prepare a soft material. The mixture was stirred and mixed uniformly at a stirring speed of 100 r / min and a shear speed of 1200 r / min. (4) The soft material was injected into an extrusion spheronizer to form pills. The spheronizer parameters were as follows: the extrusion screen was selected to be 0.8 mm, the spheronization parameter was 600 rpm, the time was 200 s, the pills were dried to a constant weight, and 16-40 mesh pills were selected through screening. Theoretically, 10,000 g of pills could be obtained, and the actual pill yield was more than 95%; (5) 64 g of methacrylic acid-ethyl acrylate copolymer, 6.4 g of plasticizer, and 19.2 g of anti-sticking agent were dissolved in 401.1 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 4% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 3 hours to obtain tamsulosin hydrochloride enteric-coated pills; and the capsules were filled to obtain tamsulosin hydrochloride sustained-release capsules.

[0028] Example 2: A tamsulosin hydrochloride sustained-release capsule, the composition of each capsule is shown in the following table: A method for preparing the above-mentioned tamsulosin hydrochloride sustained-release capsules comprises the following steps: (1) Add 100 g of water to a stainless steel barrel and heat to 50°C. Then add 2 g of tamsulosin hydrochloride and stir until completely dissolved at a stirring speed of 120 r / min. (2) Add 1104 g of microcrystalline cellulose, 276 g of starch, and 98 g of anti-sticking agent to a wet mixer and stir until uniformly mixed. Stir and mix until uniformly mixed. The stirring speed is 100 r / min and the shear speed is 1200 r / min. Then add tamsulosin hydrochloride solution for 1 to 3 minutes. (3) 100 g of methacrylic acid-ethyl acrylate copolymer and 10 g of plasticizer were added to 1 L of water and mixed uniformly to prepare a polymer solution. The polymer solution was added to a wet mixer and stirred and sheared to prepare a soft material. The mixture was stirred and mixed uniformly at a stirring speed of 100 r / min and a shear speed of 1200 r / min. (4) The soft material was injected into an extrusion spheronizer to form pills. The spheronizer parameters were as follows: the extrusion screen was selected to be 0.8 mm, the spheronization parameter was 600 rpm, the time was 200 s, the pills were dried to a constant weight, and 16-40 mesh pills were selected through screening. Theoretically, 10,000 g of pills could be obtained, and the actual pill yield was more than 98%; (5) 64 g of methacrylic acid-ethyl acrylate copolymer, 6.4 g of plasticizer, and 19.2 g of anti-sticking agent were dissolved in 401.1 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 4% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 3 hours to obtain tamsulosin hydrochloride enteric-coated pills; and the capsules were filled to obtain tamsulosin hydrochloride sustained-release capsules.

[0029] Example 3: A tamsulosin hydrochloride sustained-release capsule, the composition of each capsule is shown in the following table: A method for preparing the above-mentioned tamsulosin hydrochloride sustained-release capsules comprises the following steps: (1) Add 100 g of water to a wet mixer and heat to 50°C. Then add 2 g of tamsulosin hydrochloride and stir until completely dissolved. The stirring speed is 120 r / min. (2) Add 1280g of microcrystalline cellulose and 98g of anti-adhesive agent into a wet mixer and stir and mix them evenly. Stir and mix them evenly at a stirring speed of 100r / min and a shear speed of 1200r / min. Then add tamsulosin hydrochloride solution for 1 to 3 minutes. (3) Add 200g of methacrylic acid-ethyl acrylate copolymer and 20g of plasticizer into 1L of water and mix them evenly to prepare a polymer solution. Add the polymer solution into a wet mixer and stir and shear to prepare a soft material. Stir and mix them evenly at a stirring speed of 100r / min and a shear speed of 1200r / min. (4) The soft material was injected into an extrusion spheronizer to form pills. The spheronizer parameters were as follows: the extrusion screen was selected to be 0.8 mm, the spheronization parameter was 400 rpm, the time was 150 s, the pills were dried to a constant weight, and 16-45 mesh pills were selected through screening. Theoretically, 10,000 g of pills could be obtained, and the actual pill yield was more than 98%; (5) 64 g of methacrylic acid-ethyl acrylate copolymer, 12.8 g of plasticizer, and 19.2 g of anti-sticking agent were dissolved in 394.7 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 4% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 3 hours to obtain tamsulosin hydrochloride enteric-coated pills; and the capsules were filled to obtain tamsulosin hydrochloride sustained-release capsules.

[0030] Example 4: A tamsulosin hydrochloride sustained-release capsule, the composition of each capsule is shown in the following table: A method for preparing the above-mentioned tamsulosin hydrochloride sustained-release capsules comprises the following steps: (1) Add 100 g of water to a wet mixer and heat to 50°C. Then add 2 g of tamsulosin hydrochloride and stir until completely dissolved. The stirring speed is 120 r / min. (2) Add 1041.6 g of microcrystalline cellulose, 260.4 g of starch, and 98 g of anti-sticking agent to a wet mixer and stir until uniformly mixed at a stirring speed of 100 r / min and a shear speed of 1200 r / min; then add tamsulosin hydrochloride solution for 1 to 3 minutes; (3) 180 g of methacrylic acid-ethyl acrylate copolymer and 18 g of plasticizer were added to 1 L of water and mixed uniformly to prepare a polymer solution. The polymer solution was added to a wet mixer and stirred and sheared to prepare a soft material. The stirring speed was 100 r / min and the shear speed was 1200 r / min. (4) The soft material was injected into an extrusion spheronizer to form pills. The spheronizer parameters were as follows: the extrusion screen was selected to be 0.8 mm, the spheronization parameter was 500 rpm, the time was 180 s, the pills were dried to a constant weight, and 16-45 mesh pills were selected through screening. Theoretically, 10,000 g of pills could be obtained, and the actual pill yield was more than 95%; (5) 48 g of methacrylic acid-ethyl acrylate copolymer, 9.6 g of plasticizer, and 14.4 g of anti-sticking agent were dissolved in 296 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 3% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 8 hours to obtain tamsulosin hydrochloride enteric-coated pills; and the capsules were filled to obtain tamsulosin hydrochloride sustained-release capsules.

[0031] Example 5: A tamsulosin hydrochloride sustained-release capsule, the composition of each capsule is shown in the following table: A method for preparing the above-mentioned tamsulosin hydrochloride sustained-release capsules comprises the following steps: (1) Add 100 g of water to a wet mixer and heat to 50°C. Then add 2 g of tamsulosin hydrochloride and stir until completely dissolved. The stirring speed is 120 r / min. (2) Add 696 g of microcrystalline cellulose, 696 g of starch, and 98 g of anti-sticking agent to a wet mixer and stir until uniformly mixed at a stirring speed of 100 r / min and a shear speed of 1200 r / min; then add tamsulosin hydrochloride solution for 1 to 3 minutes; (3) 100 g of methacrylic acid-ethyl acrylate copolymer and 10 g of plasticizer were added to 1 L of water and mixed uniformly to prepare a polymer solution. The polymer solution was added to a wet mixer and stirred and sheared to prepare a soft material. The stirring speed was 100 r / min and the shear speed was 1200 r / min. (4) The soft material was injected into an extrusion spheronizer to form pills. The spheronizer parameters were as follows: the extrusion screen was selected to be 0.8 mm, the spheronization parameter was 400 rpm, the time was 120 s, the pills were dried to a constant weight, and 16-45 mesh pills were selected through screening. Theoretically, 10,000 g of pills could be obtained, and the actual pill yield was more than 85%; (5) 48 g of methacrylic acid-ethyl acrylate copolymer, 4.8 g of plasticizer, and 9.6 g of anti-sticking agent were dissolved in 305.6 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 3% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 8 hours to obtain tamsulosin hydrochloride enteric-coated pills; and the capsules were filled to obtain tamsulosin hydrochloride sustained-release capsules.

[0032] Example 6: A tamsulosin hydrochloride sustained-release capsule, the composition of each capsule is shown in the following table: A method for preparing the above-mentioned tamsulosin hydrochloride sustained-release capsules comprises the following steps: (1) Add 100 g of water to a wet mixer and heat to 50°C. Then add 2 g of tamsulosin hydrochloride and stir until completely dissolved. The stirring speed is 120 r / min. (2) Add 1284 g of microcrystalline cellulose, 256.8 g of starch, and 98 g of anti-adherent agent to a wet mixer and stir and mix them evenly at a stirring speed of 100 r / min and a shear speed of 1200 r / min; then add tamsulosin hydrochloride solution for 1 to 3 minutes; (3) Add 180 g of methacrylic acid-ethyl acrylate copolymer and 36 g of plasticizer to 1 L of water and mix them evenly to prepare a polymer solution, and add the polymer solution to a wet mixer and stir and shear to prepare a soft material at a stirring speed of 100 r / min and a shear speed of 1200 r / min; (4) The soft material was injected into an extrusion spheronizer to form pills. The spheronizer parameters were as follows: the extrusion screen was selected to be 1.0 mm, the spheronization parameter was 480 rpm, the time was 150 s, the pills were dried to a constant weight, and 16-45 mesh pills were selected through screening. Theoretically, 10,000 g of pills could be obtained, and the actual pill yield was more than 85%; (5) Dissolve 48 g of methacrylic acid-ethyl acrylate copolymer and 4.8 g of plasticizer in 315.2 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 3% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 8 hours to obtain tamsulosin hydrochloride enteric-coated pills; and the capsules were filled to obtain tamsulosin hydrochloride sustained-release capsules.

[0033] Example 7: A tamsulosin hydrochloride sustained-release capsule, the composition of each capsule is shown in the following table: A method for preparing the above-mentioned tamsulosin hydrochloride sustained-release capsules comprises the following steps: (1) Add 100 g of water to a wet mixer and heat to 50°C. Then add 2 g of tamsulosin hydrochloride and stir until completely dissolved. The stirring speed is 120 r / min. (2) Add 1284 g of microcrystalline cellulose, 256.8 g of starch, and 98 g of an anti-sticking agent to a wet mixer and stir until uniformly mixed at a stirring speed of 100 r / min and a shear speed of 1200 r / min; then add tamsulosin hydrochloride solution for 1 to 3 minutes; (3) 180 g of methacrylic acid-ethyl acrylate copolymer and 36 g of plasticizer were added to 1 L of water and mixed uniformly to prepare a polymer solution. The polymer solution was added to a wet mixer and stirred and sheared to prepare a soft material. The stirring speed was 100 r / min and the shear speed was 1200 r / min. (4) The soft material was injected into an extrusion spheronizer to form pills. The spheronizer parameters were as follows: the extrusion screen was selected to be 1.0 mm, the spheronization parameter was 480 rpm, the time was 150 s, the pills were dried to a constant weight, and 16-45 mesh pills were selected through screening. Theoretically, 10,000 g of pills could be obtained, and the actual pill yield was more than 85%; (5) 48 g of methacrylic acid-ethyl acrylate copolymer, 4.8 g of plasticizer, and 9.6 g of anti-sticking agent were dissolved in 305.6 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 3% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 8 hours to obtain tamsulosin hydrochloride enteric-coated pills; and the capsules were filled to obtain tamsulosin hydrochloride sustained-release capsules.

[0034] Comparative Example 1: Comparative Example 1 Compared with Example 1, the water temperature when dissolving tamsulosin hydrochloride is 37° C., comprising the following steps: (1) Add 100 g of water to a wet mixer and heat to 37°C, then add 0.5 g of tamsulosin hydrochloride and stir to disperse at a stirring speed of 120 r / min; (2) Add 1024 g of microcrystalline cellulose, 256 g of starch, and 153 g of an anti-sticking agent to a wet mixer and stir until uniformly mixed at a stirring speed of 100 r / min and a shear speed of 1200 r / min for 10 minutes; then add tamsulosin hydrochloride solution for 1 to 3 minutes; (3) 150 g of methacrylic acid-ethyl acrylate copolymer and 1.5 g of plasticizer were added to 1 L of water and mixed uniformly to prepare a polymer solution. The polymer solution was added to a wet mixer and stirred and sheared to prepare a soft material. The stirring speed was 100 r / min and the shear speed was 1200 r / min. (4) The soft material was injected into an extrusion spheronization machine to form pills. The spheronization machine parameters were as follows: the extrusion screen was selected to be 1.0 mm, the spheronization parameter was 600 rpm, and the time was 200 s. The pills were dried to a moisture content of ≤3.0% (rapid moisture meter, 105°C, AUTO), and 16-45 mesh pills were selected through screening. Theoretically, 2500 pills could be obtained, and the actual pill yield was 98%; (5) 64 g of methacrylic acid-ethyl acrylate copolymer, 12.8 g of plasticizer, and 19.2 g of anti-sticking agent were dissolved in 394.7 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 4% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 3 hours to prepare tamsulosin hydrochloride enteric-coated pills; and after capsule filling, tamsulosin hydrochloride sustained-release capsules were obtained.

[0035] Comparative Example 2: Comparative Example 2 Compared with Example 1, the water temperature when dissolving tamsulosin hydrochloride is 70° C., comprising the following steps: (1) Add 100 g of water to a wet mixer and heat to 70°C. Then add 2 g of tamsulosin hydrochloride and stir until completely dissolved. The stirring speed is 120 r / min. (2) Add 1024 g of microcrystalline cellulose, 256 g of starch, and 153 g of an anti-sticking agent to a wet mixer and stir until uniformly mixed at a stirring speed of 100 r / min and a shear speed of 1200 r / min for 10 minutes; then add tamsulosin hydrochloride solution for 1 to 3 minutes; (3) 150 g of methacrylic acid-ethyl acrylate copolymer and 1.5 g of plasticizer were added to 1 L of water and mixed uniformly to prepare a polymer solution. The polymer solution was added to a wet mixer and stirred and sheared to prepare a soft material. The stirring speed was 100 r / min and the shear speed was 1200 r / min. (4) The soft material was injected into an extrusion spheronizer to form pills. The spheronizer parameters were as follows: 1.0 mm extrusion screen, 600 rpm, and 200 s s spheronization. The pills were dried to a moisture content of ≤ 3.0% (rapid moisture meter, 105°C, AUTO). 16-45 mesh pills were screened and the pill yield was 9%. (5) 64 g of methacrylic acid-ethyl acrylate copolymer, 12.8 g of plasticizer, and 19.2 g of anti-sticking agent were dissolved in 394.7 g of water to prepare a coating solution; (6) The pills were coated with a coating solution according to a 4% weight gain of the pills. The coating was carried out using a fluidized bed bottom spray coating method. The conditions for the fluidized bed bottom spray coating were: material temperature 30±3°C, atomization pressure 1.0 bar; after coating, the pellets were transferred to an oven at 50°C for curing for 3 hours to prepare tamsulosin hydrochloride enteric-coated pills; and after capsule filling, tamsulosin hydrochloride sustained-release capsules were obtained.

[0036] Comparative Example 3: Comparative Example 3 is the reference preparation of tamsulosin hydrochloride sustained-release capsules, which is the original preparation "Hal".

[0037] Test example: Test the solubility of tamsulosin hydrochloride in water at a temperature of 37.5 to 90°C. Figure 1 .

[0038] The dissolution curves of Examples 1 to 7 and Comparative Examples 1 to 3 were tested under standard medium conditions and a test period of 2 to 8 hours. The test results are shown in FIG. Figure 2 .

[0039] The dissolution curves of Comparative Example 3 and Example 1 were tested at pH 4.0 for 24 hours. The test period was 6 to 24 hours. The test results are shown in Table 1. Figure 3 .

[0040] The dissolution curves of Comparative Example 3 and Example 1 were tested at pH 6.8 for 8 hours. The test period was 2 to 8 hours. The test results are shown in Figure 4 .

[0041] like Figure 1 As shown, Figure 1 The figure shows the solubility of tamsulosin hydrochloride in water at different temperatures. It can be seen from the figure that when the water temperature reaches 50°C, the solubility of tamsulosin hydrochloride in water increases extremely significantly. Thereafter, the solubility of tamsulosin hydrochloride increases with increasing temperature, but the rate of increase is slow.

[0042] like Figure 2 As shown, the similarity factors f2 of the dissolution curves of Examples 1 to 7 and the dissolution curve of Comparative Example 3 (original formulation) are all greater than 50, indicating that the dissolution of the tamsulosin hydrochloride sustained-release capsules prepared in the present invention is consistent with that of the original formulation.

[0043] Comparative Example 2 is a technical solution for dissolving tamsulosin hydrochloride in water at 70°C. The results show that the display factor of the dissolution curve of Comparative Example 2 and the dissolution curve of Comparative Example 3 is less than 50, which indicates that when the water temperature exceeds 70°C, the dissolution performance of the prepared tamsulosin hydrochloride sustained-release capsules cannot be consistent with the original formulation and cannot meet the consistency requirements. After analysis, it was found that the problem caused by the above-mentioned reason is that the starch used to assist in sustained release has gelatinized. The gelatinized starch will cause the sustained-release performance of the tamsulosin hydrochloride sustained-release capsules to change significantly, thereby significantly changing the dissolution performance of the sustained-release agent.

[0044] like Figure 3 As shown, Figure 3 The dissolution curves of Example 1 and Comparative Example 3 at different pH values ​​are shown in the figure. The results show that the tamsulosin hydrochloride sustained-release capsules prepared in the present invention have stable sustained-release properties in an environment with a pH value of 1 to 7.

[0045] As can be seen from Examples 1-7 and the technical solutions of Comparative Example 1, the addition of starch can significantly reduce the amount of polymer and microcrystalline cellulose used, with the polymer reduction reaching 50%. Since the cost of polymer is much higher than that of starch, the cost of using starch, microcrystalline cellulose, and polymer as the backbone material is much lower than that of using only microcrystalline cellulose and polymer as the sustained-release material. However, increasing the starch ratio also leads to a decrease in pill yield. Therefore, a starch:microcrystalline cellulose ratio of 1:4 is preferred, achieving a yield greater than 98%. At the same time, the polymer usage can be reduced by up to approximately 50% compared to a starch-free formulation.

[0046] In addition, after an in-depth analysis of starch, it was found that the content of amylopectin in the starch used has an important influence on the yield of pills. When the content of amylopectin in starch is above 90%, it can have a better auxiliary skeleton sustained-release effect and can reduce the amount of polymer by up to 50%. Generally, when the amylopectin content is around 70%, the amount of polymer can be reduced by up to about 70%.

[0047] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent transformation made to the above embodiment based on the technical essence of the present invention still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A tamsulosin hydrochloride sustained-release capsule, characterized in that: The components of the pills, calculated by mass percentage, include: 0.1-0.2% of tamsulosin hydrochloride, 5-20% of sustained-release matrix material, and 80-95% of filler. The sustained-release matrix material is methacrylic acid-ethyl acrylate copolymer, and the filler includes starch and microcrystalline cellulose.

2. The tamsulosin hydrochloride sustained-release capsule according to claim 1, characterized in that: Methacrylic acid-ethyl acrylate copolymer Methacrylic acid-ethyl acrylate copolymer is one of Eudragit L30D-55 and Eudragit L100-55.

3. The tamsulosin hydrochloride sustained-release capsule according to claim 1, characterized in that: The sustained-release matrix material also includes plasticizers and anti-adherent agents.

4. The tamsulosin hydrochloride sustained-release capsule according to claim 3, characterized in that: The plasticizer is one or both of triethyl citrate and PEG400; and the anti-sticking agent is talc.

5. A method for preparing the tamsulosin hydrochloride sustained-release capsules according to any one of claims 1 to 4, characterized in that: The following steps are involved: (1) The filler and anti-adhesive agent are mixed evenly, and then tamsulosin hydrochloride solution is added, and then methacrylic acid-ethyl acrylate copolymer and plasticizer are added to prepare a soft material, and the soft material is extruded and rolled into a round shape to prepare a pill; The temperature of the water used for preparing the tamsulosin hydrochloride solution is preferably 50-70°C; (2) Methacrylic acid-ethyl acrylate copolymer is dispersed in water and a plasticizer and an anti-sticking agent are added to prepare a coating solution, the coating solution is used to coat the pills, and the capsules are filled to prepare tamsulosin hydrochloride sustained-release capsules.

6. The preparation method according to claim 5, characterized in that: The soft material was prepared using a wet mixing granulation device, and the extrusion and spheronization of the pills was performed using an extrusion and spheronization machine. The conditions of the wet mixing granulation device were: stirring speed 100-150 r / min, cutting speed 1000-1500 r / min; the parameters of the extrusion and spheronization machine were: extrusion screen 0.8-1.0 mm, spheronization 400-600 rpm, and time 100-200 s.

7. The preparation method according to claim 5 or 6, characterized in that: The particle size of the pills is 16~45 mesh.

8. The preparation method according to claim 5, characterized in that: The coating process adopts fluidized bed bottom spray coating method.

9. The preparation method according to claim 5, characterized in that: The coating treatment conditions are: temperature of 25~35℃, and curing temperature of 40~50℃.

10. The preparation method according to claim 5, characterized in that: The coating weight gain is 2.5~4.5% of the pill mass.

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