Ibuprofen granules and production process thereof

Abstract

The invention provides ibuprofen granules and a production process thereof, and relates to the field of medicines. The ibuprofen granule is prepared from the following raw and auxiliary materials in parts by weight: 95 to 105 parts of ibuprofen, 800 to 950 parts of filler and 100 to 105 parts of adhesive, the adhesive is prepared from hydroxypropyl methylcellulose, polysorbate and purified water. The mass ratio of the hydroxypropyl methylcellulose to the polysorbate to the purified water in the adhesive is (1.9-2.1): (0.7-0.8): (95-105); the polysorbate is prepared from polysorbate 80 and polysorbate 85 according to the mass ratio of 1 to (0.4 to 0.6). The filling agent is prepared from aspartame, low-substituted hydroxypropyl cellulose and cane sugar according to the mass ratio of (15 to 25) to (15 to 25) to (800 to 900). The ibuprofen granules prepared by the preparation method disclosed by the invention have better analgesic and anti-inflammatory effects, and the ibuprofen granules prepared by the preparation method disclosed by the invention are good in stability.

Description

Technical Field

[0001] The invention relates to the field of medicines, and in particular to ibuprofen particles and a production process thereof. Background Art

[0002] Ibuprofen, chemical name: 2-methyl-4-(2-methylpropyl)phenylacetic acid, molecular formula C 13 H 18 O2, molecular weight 206.28. Ibuprofen is the world's first clinically used profen drug and is still widely used. It is recognized as one of the safest non-steroidal anti-inflammatory drugs, with multiple analgesic, anti-inflammatory and antipyretic effects. Its main mechanism of action is to inhibit the activity of cyclooxygenase, thereby reducing the synthesis of prostaglandins, effectively reducing tissue congestion and swelling caused by prostaglandins, and reducing the sensitivity of peripheral nerves to pain; in addition, ibuprofen also exerts an antipyretic effect by acting on the temperature regulation center of the hypothalamus.

[0003] Ibuprofen granules are mainly used to relieve mild to moderate pain such as headache, arthralgia, migraine, toothache, myalgia, neuralgia, dysmenorrhea. They are also used for the fever caused by the common cold or influenza. Existing ibuprofen preparations still have room for improvement in terms of drug efficacy, stability, etc. Therefore, the present invention develops a new ibuprofen granule and process, which has important clinical significance and better meets market demand. Summary of the invention

[0004] In view of this, the present invention proposes an ibuprofen granule and a production process thereof to improve the analgesic and anti-inflammatory effects, bioavailability and stability of the ibuprofen granule.

[0005] The technical solution of the present invention is achieved in this way:

[0006] An ibuprofen granule comprises the following raw and auxiliary materials in parts by weight: 95-105 parts of ibuprofen, 800-950 parts of a filler, and 100-105 parts of a binder; the binder is made of hypromellose, polysorbate and purified water.

[0007] Preferably, the mass ratio of hypromellose, polysorbate and purified water in the adhesive is 1.9-2.1:0.7-0.8:95-105; the polysorbate consists of polysorbate 80 and polysorbate 85 in a mass ratio of 1:0.4-0.6.

[0008] Preferably, the filler consists of aspartame, low-substituted hydroxypropyl cellulose and sucrose in a mass ratio of 15-25:15-25:800-900.

[0009] Preferably, the ibuprofen particles further contain sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose, the total weight of the three added is 5%-10% of the weight of ibuprofen, and the mass ratio of sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose is 3-5:7-9:1.

[0010] The production process of the ibuprofen granules according to any one of the present invention comprises the following steps:

[0011] (1) Weighing polysorbate, adding 60% to 80% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hydroxypropyl methylcellulose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive;

[0012] (2) After sucrose is crushed, ibuprofen and filler are placed in a crushing and granulating machine for sieving; the sifted raw and auxiliary materials are added to a high-speed mixing granulator, and the stirring speed and the cutting speed are set to be high, and the mixing is mixed; after the mixing is uniform, the binder in step (1) is added, and the stirring speed and the cutting speed are set to be low, and the mixing is stirred and mixed; the above soft materials are added to a wet granulator for granulation;

[0013] (3) After granulation, the material is added into a fluidized bed and dried;

[0014] (4) sieving the dried particles and refining the coarse particles;

[0015] (5) The whole granules are mixed in a mixer and discharged to obtain ibuprofen granules.

[0016] Furthermore, in step (2), the stirring speed and the cutting speed are both 35-45 rpm; the stirring speed and the cutting speed are both 8-12 rpm.

[0017] Furthermore, in step (3), the drying time is 8-12 minutes, the air inlet temperature is 25-35° C., and the air induced velocity is 50%-75%.

[0018] Furthermore, in step (4), the sieving is specifically: sieving through an upper 16-mesh sieve and a lower 40-mesh sieve; and in step (5), the mixing time is 4-6 minutes.

[0019] Furthermore, the production process of the ibuprofen granules comprises the following steps:

[0020] (1) Weighing polysorbate, adding 60% to 80% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hydroxypropyl methylcellulose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive;

[0021] (2) pulverizing sucrose with a universal grinder through a 70-90 mesh sieve, and sieving ibuprofen and fillers in a pulverizer, with a sieve aperture of 0.8-1.2 mm; adding the sieved raw and auxiliary materials to a high-speed mixing granulator, setting the stirring speed and the cutting speed to high speed, and mixing for 5-10 minutes; after mixing evenly, adding the binder in step (1), setting the stirring speed and the cutting speed to low speed, and stirring and mixing for 20-40 seconds; adding the above soft materials to a wet granulator, and swaying granulating through a 20-30 mesh sieve;

[0022] (3) After granulation, the inlet air temperature is 25-35°C, the induced air speed is 50%-75%, and the material is added into the fluidized bed and dried for 8-12 minutes;

[0023] (4) Sieve the dried granules through a 16-mesh upper sieve and a 40-mesh lower sieve to size the coarse granules;

[0024] (5) The granules are then placed in a three-dimensional oscillating mixer for mixing for 4-6 minutes; the mixture is discharged to obtain the target ibuprofen granules.

[0025] Furthermore, in step (2), sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose are added into a high-speed mixing granulator.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention adopts certain ratio of hydroxypropyl methylcellulose, polysorbate (polysorbate 80 and polysorbate 85 composition) and purified water to form adhesive, and specific ratio of aspartame, low-substituted hydroxypropyl cellulose and sucrose to form filler, and the prepared ibuprofen granules have better analgesic and anti-inflammatory effects, and the accelerated test results show that the ibuprofen granules prepared by the present invention have good stability. And the present invention adds certain ratio of sulfobutyl beta-cyclodextrin, glycine methyl ester, D-galactose, effectively improves drug inclusion, significantly improves pharmacokinetic properties, enhances the bioavailability of medicine, promotes body metabolism simultaneously, and further enhances ibuprofen granules analgesic and anti-inflammatory effects. DETAILED DESCRIPTION

[0028] In order to better understand the technical content of the present invention, specific embodiments are provided below to further illustrate the present invention.

[0029] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0030] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources.

[0031] Example 1

[0032] An ibuprofen granule comprises the following raw materials and auxiliary materials in parts by weight: 100 parts of ibuprofen, 897 parts of a filler, and 101.75 parts of a binder; the binder is made of hypromellose, polysorbate, and purified water; the mass ratio of the hypromellose, polysorbate, and purified water in the binder is 2.0:0.75:99; the polysorbate is composed of polysorbate 80 and polysorbate 85 in a mass ratio of 1:0.5; the filler is composed of aspartame, low-substituted hydroxypropyl cellulose, and sucrose in a mass ratio of 20:20:857;

[0033] The production process of ibuprofen granules includes the following steps:

[0034] (1) Weighing polysorbate, adding 74% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hypromellose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive;

[0035] (2) pulverizing sucrose with a universal grinder through an 80-mesh sieve, and sieving ibuprofen, pulverized sucrose, and aspartame in a pulverizer and granulator, with a sieve aperture of 1.0 mm; adding the sieved raw and auxiliary materials to a high-speed mixing granulator, setting the stirring speed and the cutting speed to high speed, and mixing for 8 minutes; after mixing evenly, adding the adhesive in step (1), setting the stirring speed and the cutting speed to low speed, and stirring and mixing for 30 seconds; adding the above soft materials to a wet granulator, and swaying granulating through a 24-mesh sieve;

[0036] (3) After granulation, the inlet air temperature is 30°C ± 5°C, the induced air speed is 50%-75%, and the material is added into the fluidized bed and dried for 10 minutes;

[0037] (4) Sieve the dried granules through a 16-mesh upper sieve and a 40-mesh lower sieve to size the coarse granules;

[0038] (5) The granules were then placed in a three-dimensional oscillating mixer for mixing for 5 minutes; the mixture was discharged to obtain the target ibuprofen granules.

[0039] Example 2

[0040] An ibuprofen granule comprises the following raw materials and auxiliary materials in parts by weight: 95 parts of ibuprofen, 855 parts of a filler, and 102.7 parts of a binder; the binder is made of hypromellose, polysorbate, and purified water; the mass ratio of the hypromellose, polysorbate, and purified water in the binder is 1.9:0.8:100; the polysorbate is composed of polysorbate 80 and polysorbate 85 in a mass ratio of 1:0.4; the filler is composed of aspartame, low-substituted hydroxypropyl cellulose, and sucrose in a mass ratio of 15:25:815;

[0041] The production process of ibuprofen granules includes the following steps:

[0042] (1) Weighing polysorbate, adding 75% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hypromellose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive;

[0043] (2) pulverizing sucrose with a universal grinder through an 80-mesh sieve, and sieving ibuprofen, pulverized sucrose, and aspartame in a pulverizer and granulator, with a sieve aperture of 1.0 mm; adding the sieved raw and auxiliary materials to a high-speed mixing granulator, setting the stirring speed and the cutting speed to high speed, and mixing for 8 minutes; after mixing evenly, adding the adhesive in step (1), setting the stirring speed and the cutting speed to low speed, and stirring and mixing for 30 seconds; adding the above soft materials to a wet granulator, and swaying granulating through a 24-mesh sieve;

[0044] (3) After granulation, the inlet air temperature is 30°C ± 5°C, the induced air speed is 50%-75%, and the material is added into the fluidized bed and dried for 10 minutes;

[0045] (4) Sieve the dried granules through a 16-mesh upper sieve and a 40-mesh lower sieve to size the coarse granules;

[0046] (5) The granules were then placed in a three-dimensional oscillating mixer for mixing for 5 minutes; the mixture was discharged to obtain the target ibuprofen granules.

[0047] Example 3

[0048] An ibuprofen granule comprises the following raw and auxiliary materials in parts by weight: 105 parts of ibuprofen, 940 parts of a filler, and 99.8 parts of a binder; the binder is made of hypromellose, polysorbate, and purified water;

[0049] The mass ratio of hypromellose, polysorbate and purified water in the adhesive is 2.1:0.7:97; the polysorbate is composed of polysorbate 80 and polysorbate 85 in a mass ratio of 1:0.6;

[0050] The filler is composed of aspartame, low-substituted hydroxypropyl cellulose and sucrose in a mass ratio of 25:15:900;

[0051] The production process of ibuprofen granules includes the following steps:

[0052] (1) Weighing polysorbate, adding 72% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hypromellose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive;

[0053] (2) pulverizing sucrose with a universal grinder through an 80-mesh sieve, and sieving ibuprofen, pulverized sucrose, and aspartame in a pulverizer and granulator, with a sieve aperture of 1.0 mm; adding the sieved raw and auxiliary materials to a high-speed mixing granulator, setting the stirring speed and the cutting speed to high speed, and mixing for 8 minutes; after mixing evenly, adding the adhesive in step (1), setting the stirring speed and the cutting speed to low speed, and stirring and mixing for 30 seconds; adding the above soft materials to a wet granulator, and swaying granulating through a 24-mesh sieve;

[0054] (3) After granulation, the inlet air temperature is 30°C ± 5°C, the induced air speed is 50%-75%, and the material is added into the fluidized bed and dried for 10 minutes;

[0055] (4) Sieve the dried granules through a 16-mesh upper sieve and a 40-mesh lower sieve to size the coarse granules;

[0056] (5) The granules were then placed in a three-dimensional oscillating mixer for mixing for 5 minutes; the mixture was discharged to obtain the target ibuprofen granules.

[0057] Example 4

[0058] The main difference from Example 1 is the production process:

[0059] An ibuprofen granule comprises the following raw materials and auxiliary materials in parts by weight: 100 parts of ibuprofen, 897 parts of a filler, and 101.75 parts of a binder; the binder is made of hypromellose, polysorbate, and purified water; the mass ratio of the hypromellose, polysorbate, and purified water in the binder is 2.0:0.75:99; the polysorbate is composed of polysorbate 80 and polysorbate 85 in a mass ratio of 1:0.5; the filler is composed of aspartame, low-substituted hydroxypropyl cellulose, and sucrose in a mass ratio of 20:20:857;

[0060] The production process of ibuprofen granules includes the following steps:

[0061] (1) Weighing polysorbate, adding 74% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hypromellose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive;

[0062] (2) pulverizing sucrose with a universal grinder through an 80-mesh sieve, and sieving ibuprofen, pulverized sucrose, and aspartame in a pulverizer and granulator, with a sieve aperture of 1.0 mm; adding the sieved raw and auxiliary materials to a high-speed mixing granulator, setting the stirring speed and the cutting speed to high speed, and mixing for 5 minutes; after mixing evenly, adding the adhesive in step (1), setting the stirring speed and the cutting speed to low speed, and stirring and mixing for 40 seconds; adding the above soft materials to a wet granulator, and swaying granulating through a 24-mesh sieve;

[0063] (3) After granulation, the inlet air temperature is 30°C ± 5°C, the induced air speed is 50%-75%, and the material is added into the fluidized bed and dried for 8 minutes;

[0064] (4) Sieve the dried granules through a 16-mesh upper sieve and a 40-mesh lower sieve to size the coarse granules;

[0065] (5) The whole granules were placed in a three-dimensional oscillating mixer for mixing for 4 minutes; the material was discharged to obtain the target ibuprofen granules.

[0066] Example 5

[0067] The main difference from Example 1 is the production process:

[0068] An ibuprofen granule comprises the following raw materials and auxiliary materials in parts by weight: 100 parts of ibuprofen, 897 parts of a filler, and 101.75 parts of a binder; the binder is made of hypromellose, polysorbate, and purified water; the mass ratio of the hypromellose, polysorbate, and purified water in the binder is 2.0:0.75:99; the polysorbate is composed of polysorbate 80 and polysorbate 85 in a mass ratio of 1:0.5; the filler is composed of aspartame, low-substituted hydroxypropyl cellulose, and sucrose in a mass ratio of 20:20:857;

[0069] The production process of ibuprofen granules includes the following steps:

[0070] (1) Weighing polysorbate, adding 74% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hypromellose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive;

[0071] (2) pulverizing sucrose with a universal grinder through an 80-mesh sieve, and sieving ibuprofen, pulverized sucrose, and aspartame in a pulverizer and granulator, with a sieve aperture of 1.0 mm; adding the sieved raw and auxiliary materials to a high-speed mixing granulator, setting the stirring speed and the cutting speed to high speed, and mixing for 10 minutes; after uniform mixing, adding the adhesive in step (1), setting the stirring speed and the cutting speed to low speed, and stirring and mixing for 20 seconds; adding the above soft materials to a wet granulator, and swaying granulating through a 24-mesh sieve;

[0072] (3) After granulation, the inlet air temperature is 30°C ± 5°C, the induced air speed is 50%-75%, and the material is added into the fluidized bed and dried for 12 minutes;

[0073] (4) Sieve the dried granules through a 16-mesh upper sieve and a 40-mesh lower sieve to size the coarse granules;

[0074] (5) The granules were then placed in a three-dimensional oscillating mixer for mixing for 6 minutes; the mixture was discharged to obtain the target ibuprofen granules.

[0075] Example 6

[0076] An ibuprofen granule comprises the following raw and auxiliary materials in parts by weight:

[0077] 100 parts of ibuprofen, 890 parts of filler, 101.75 parts of binder, and 7.8 parts of compound mixture; the binder is made of hypromellose, polysorbate and purified water;

[0078] The composite mixture consists of sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose, and the mass ratio of sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose is 4:8:1;

[0079] The mass ratio of hypromellose, polysorbate and purified water in the adhesive is 2.0:0.75:99; the polysorbate is composed of polysorbate 80 and polysorbate 85 in a mass ratio of 1:0.5;

[0080] The filler consists of aspartame, low-substituted hydroxypropyl cellulose and sucrose in a mass ratio of 15:25:850.

[0081] The production process of ibuprofen granules includes the following steps:

[0082] (1) Weighing polysorbate, adding 74% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hypromellose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive;

[0083] (2) pulverizing sucrose with a universal grinder through an 80-mesh sieve, and sieving ibuprofen, pulverized sucrose, and aspartame in a pulverizer and granulator, with a sieve aperture of 1.0 mm; adding the sieved raw and auxiliary materials to a high-speed mixing granulator, setting the stirring speed and the cutting speed to high speed, and mixing for 8 minutes; after mixing evenly, adding the adhesive in step (1), setting the stirring speed and the cutting speed to low speed, and stirring and mixing for 30 seconds; adding the above soft materials to a wet granulator, and swaying granulating through a 24-mesh sieve;

[0084] (3) After granulation, the inlet air temperature is 30°C ± 5°C, the induced air speed is 50%-75%, and the material is added into the fluidized bed and dried for 10 minutes;

[0085] (4) Sieve the dried granules through a 16-mesh upper sieve and a 40-mesh lower sieve to size the coarse granules;

[0086] (5) The granules were then placed in a three-dimensional oscillating mixer for mixing for 5 minutes; the mixture was discharged to obtain the target ibuprofen granules.

[0087] Comparative Example 1

[0088] The main difference from Example 1 is that the mass ratio of hypromellose, polysorbate and purified water in the adhesive is 1.5:1.25:99.

[0089] Comparative Example 2

[0090] The main difference from Example 1 is that the filler consists of aspartame, low-substituted hydroxypropyl cellulose and sucrose in a mass ratio of 10:30:857.

[0091] Comparative Example 3

[0092] The main difference from Example 6 is that no sulfobutyl-beta-cyclodextrin is added to the compounded mixture.

[0093] An ibuprofen granule comprises the following raw and auxiliary materials in parts by weight: 100 parts of ibuprofen, 890 parts of a filler, 101.75 parts of a binder, and 7.8 parts of a compound mixture; the binder is prepared from hydroxypropyl methylcellulose, polysorbate, and purified water; the compound mixture consists of glycine methyl ester and D-galactose, and the mass ratio of glycine methyl ester to D-galactose is 1:1.

[0094] Comparative Example 4

[0095] The difference from Example 6 is that the composite mixture consists of sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose, and the mass ratio of sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose is 1:1:1.

[0096] 1. Efficacy Test

[0097] 1.1 Test subjects: ibuprofen granules prepared in Examples 1-3, Example 6, and Comparative Examples 1-4;

[0098] 1.2 Test methods

[0099] (1) Analgesia test: 60 healthy mice with a body weight range of 18-22g, half male and half female, were randomly divided into groups, with 24 mice in each group, including a control group and test groups 1-8 (corresponding to the ibuprofen particles prepared in Examples 1-3, Example 6, and Comparative Examples 1-4, respectively). The control group was given an 8% sodium carboxymethylcellulose solution (0.2ml / 10g) by gavage; each test group was given an intraperitoneal injection of 0.2ml / 10g of 0.3% acetic acid solution. One hour after the administration, each group was given an intraperitoneal injection of 0.1ml / 10g of 0.3% acetic acid solution. The number of writhing reactions in each group was observed within 15 minutes, and the analgesic percentage of each drug was calculated.

[0100] (2) Anti-inflammatory test: 60 healthy mice with a body weight range of 18-22g, half male and half female, were randomly divided into groups, with 10 mice in each group, including a model group and test groups 1-8 (corresponding to the ibuprofen particles prepared in Examples 1-3, Example 6, and Comparative Examples 1-4, respectively). The model group was given 8% sodium carboxymethylcellulose solution (0.2ml / 10g) by gavage; each test group 1-8 was given by gavage, with a dosage of 0.2ml / 10g, and the gavage was continued for 5 days; 1 hour after the last administration, 0.05mL of xylene was applied to the inner and outer sides of the right ear of each mouse to induce inflammation, and the left ear was not applied as a normal ear control. After 30 minutes, the mice were killed by cervical dislocation, and the left and right ears were cut along the auricle baseline. The discs at the same part of the left and right ears were punched out with an ear swelling puncher, and the discs were weighed immediately. The mass of the two ears was recorded, and the swelling degree of the mouse auricle was calculated.

[0101] 1.3 Test results

[0102] Table 1 Analgesia test results

[0103] Group Test subjects Mouse (pcs) Number of writhing reactions (near) Analgesia percentage Control group —— 24 10 0 Experimental Group 1 Example 1 24 3 87.50％** Experimental Group 2 Example 2 24 4 83.33％** Experimental Group 3 Example 3 24 4 83.33％** Experimental Group 4 Example 6 24 1 95.83％** Experimental Group 5 Comparative Example 1 24 7 70.83％** Experimental Group 6 Comparative Example 2 24 5 79.17％** Test Group 7 Comparative Example 3 24 4 83.33％** Experimental Group 8 Comparative Example 4 24 3 87.50％**

[0104] Note: Compared with the control group, *P<0.05, **P<0.01

[0105] Table 2 Anti-inflammatory test results

[0106] Group Test subjects Mouse (pcs) Left ear weight (mg) Right ear weight (mg) Swelling degree (mg) Model Group —— 10 13.17±1.87 31.87±3.79 18.70 Experimental Group 1 Example 1 10 13.22±1.17 20.83±3.06 7.61** Experimental Group 2 Example 2 10 13.11±1.16 22.13±3.27 9.02** Experimental Group 3 Example 3 10 13.63±1.12 22.12±3.24 8.49** Experimental Group 4 Example 6 10 13.13±1.04 16.91±3.16 3.78** Experimental Group 5 Comparative Example 1 10 12.69±1.30 26.81±3.48 14.12* Experimental Group 6 Comparative Example 2 10 12.83±1.45 26.17±3.58 13.34* Test Group 7 Comparative Example 3 10 13.38±1.38 23.66±3.15 10.28* Experimental Group 8 Comparative Example 4 10 13.61±1.39 22.81±3.59 9.20*

[0107] Note: Compared with the model group, *P<0.05, **P<0.01

[0108] The results showed that compared with the control group or the model group, the ibuprofen granules in each test group had certain analgesic and anti-inflammatory effects. The ibuprofen granules prepared in Examples 1-3 and Example 6 had good analgesic and anti-inflammatory effects, among which the ibuprofen granules prepared in Example 6 had the best analgesic and anti-inflammatory effects.

[0109] 2. Stability test

[0110] 2.1 Test subjects: ibuprofen granules prepared in Example 1 and Example 6, with a specification of 0.1 g;

[0111] Reference preparation: Ibuprofen granules, produced by Kaken Pharmaceutical Co., Ltd.; specification: 20%;

[0112] 2.2 Accelerated test conditions and methods: Use (PET / AL / PE composite film for pharmaceutical packaging) for packaging, place in a constant temperature and humidity incubator at 40℃±2℃ and relative humidity 75%±5%, take samples for testing at 1, 2, 3, and 6 months, and compare the test results with the data from October.

[0113] 2.3 Test results: See Table 3.

[0114] Table 3 Accelerated test results

[0115]

[0116] The indicators were compared with the data in October: no significant change in properties; particle size did not exceed 1.3%; loss on drying was no more than 1.1% for the self-made products and no more than 1.3% for the reference preparations; microbial limit tests were in compliance with regulations; no significant change in the content determination results, both the reference preparations and the self-made products showed a decreasing trend, and currently all met the regulations; compared with the reference preparations, the dissolution of the self-made products accelerated for 6 months was better; there was no significant increase in the impurities in the related substances; the microbial detection of each test group met the regulations. The test results show that the ibuprofen particles prepared in Example 1 and Example 6 are relatively stable under accelerated test conditions.

[0117] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An ibuprofen granule, characterized in that: The invention comprises the following raw and auxiliary materials in parts by weight: 95-105 parts of ibuprofen, 800-950 parts of a filler and 100-105 parts of a binder; the binder is made of hypromellose, polysorbate and purified water, and the mass ratio of the hypromellose, polysorbate and purified water in the binder is 1.9-2.1:0.7-0.8:95-105; the polysorbate is composed of polysorbate 80 and polysorbate 85 in a mass ratio of 1:0.4-0.

6.

2. The ibuprofen granules according to claim 1, characterized in that The filler consists of aspartame, low-substituted hydroxypropyl cellulose and sucrose in a mass ratio of 15-25:15-25:800-900.

3. The ibuprofen granules according to claim 1 or 2, characterized in that The ibuprofen particles also contain sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose, the total weight of the three being 5%-10% of the weight of ibuprofen, and the mass ratio of sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose being 3-5:7-9:

1.

4. The production process of the ibuprofen granules according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) Weighing polysorbate, adding 60% to 80% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hydroxypropyl methylcellulose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive; (2) ibuprofen and filler are placed in a pulverizer and sieved; the sieved raw and auxiliary materials are added to a high-speed mixing granulator, the stirring speed and the cutting speed are set to be high, and the mixing is carried out; after the mixing is uniform, the binder in step (1) is added, the stirring speed and the cutting speed are set to be low, and the mixing is carried out; the above soft materials are added to a wet granulator and granulated; (3) After granulation, the material is added into a fluidized bed and dried; (4) sieving the dried particles and refining the coarse particles; (5) The whole granules are mixed in a mixer and discharged to obtain ibuprofen granules.

5. The production process of ibuprofen granules according to claim 4, characterized in that, In step (2), the stirring speed and the cutting speed are both 35-45 rpm; the stirring speed and the cutting speed are both 8-12 rpm.

6. The production process of ibuprofen granules according to claim 4, characterized in that: Step (3), the drying time is 8-12 minutes, the air inlet temperature is 25-35°C, and the air induced speed is 50%-75%.

7. The production process of ibuprofen granules according to claim 4, characterized in that: In step (4), the sieving is specifically: sieving through an upper 16-mesh sieve and a lower 40-mesh sieve; and in step (5), the mixing time is 4-6 minutes.

8. The production process of ibuprofen granules according to claim 4, characterized in that: The following steps are involved: (1) Weighing polysorbate, adding 60% to 80% v / v of the prescribed amount of purified water, stirring to dissolve, then adding hydroxypropyl methylcellulose, stirring to swell, and finally adding the remaining amount of purified water to obtain an adhesive; (2) ibuprofen and filler are sieved in a pulverizer with a mesh size of 0.8-1.2 mm; the sieved raw and auxiliary materials are added to a high-speed mixing granulator, the stirring speed and the cutting speed are set to high speed, and the mixing is performed for 5-10 minutes; after the mixing is uniform, the binder in step (1) is added, the stirring speed and the cutting speed are set to low speed, and the mixing is performed for 20-40 seconds; the above soft materials are added to a wet granulator, and the granules are sieved through a 20-30 mesh screen by shaking; (3) After granulation, the inlet air temperature is 25-35°C, the induced air speed is 50%-75%, and the material is added into the fluidized bed and dried for 8-12 minutes; (4) Sieve the dried granules through a 16-mesh upper sieve and a 40-mesh lower sieve to size the coarse granules; (5) The granules are then placed in a three-dimensional oscillating mixer for mixing for 4-6 minutes; the mixture is discharged to obtain the target ibuprofen granules.

9. The production process of ibuprofen granules according to claim 4 or 8, characterized in that: Step (2), adding sulfobutyl beta-cyclodextrin, glycine methyl ester and D-galactose into a high-speed mixing granulator.

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