Voglibose tablet and preparation method therefor

Abstract

A voglibose tablet and a preparation method therefor. The voglibose tablet comprises the following raw materials in parts by weight: 1 part of voglibose, 500-540 parts of lactose, 20-35 parts of hydroxypropyl cellulose, 1-3 parts of magnesium stearate and 110-130 parts of corn starch. In the preparation method, it is selected to dissolve active pharmaceutical ingredients in an adhesive solution for spray addition, and upon testing, the problem of content uniformity of small-specification preparations is solved. Fluidized bed granulation process capable of implementing continuous operations is used; a reasonable process parameter range is set; and upon testing, the prepared tablets have good content uniformity and high dissolution rate, the drug utilization rate is improved, and the blood sugar lowering effect of voglibose can be improved. The preparation method has the advantages of continuous operation, low cost, high yield, suitability for large-scale production and the like, and the obtained voglibose tablets have good dissolution rate and content uniformity.

Description

Voglibose tablet and preparation method thereof

Technical field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a voglibose tablet and a preparation method thereof. [Background Technology]

[0002] Voglibose is an α-glucosidase inhibitor used to improve postprandial hyperglycemia in diabetic patients. Its mechanism of action is to competitively inhibit maltase, isomaltase, glycosidase, etc. on the small intestinal mucosa, reducing the decomposition of disaccharides into monosaccharides, resulting in reduced D-glucose formation, thereby delaying the digestion and absorption of starch and sucrose, lowering blood sugar, but does not cause calorie loss, so it will not cause hypoglycemia when used alone. Compared with the similar drug acarbose. Voglibose does not increase the burden on pancreatic beta cells. On the contrary, it can improve insulin resistance and slightly reduce insulin levels. Its inhibitory effect on disaccharidases (sucrase and maltase) is stronger, with higher safety and fewer gastrointestinal side effects. Therefore, this product has the advantages of being safe and effective in lowering blood sugar and has broad market prospects. However, there are few domestic manufacturers, the process is complex, a wide variety of excipients are used, and the production cost is high, which cannot meet the demand of domestic diabetic patients for voglibose tablets. Therefore, it is urgent to develop a safe, scientific, easy-to-operate, low-cost, and industrially producible voglibose tablet preparation process to provide the vast number of domestic diabetic patients with quality-controlled, low-cost, and high-quality voglibose drugs.

[0003] Although voglibose is a BCS Class III drug with good water solubility, its crystalline form, arranged in a matrix of needles, results in slow dissolution in the dissolution medium and a prolonged onset of action. Drug absorption primarily depends on its solubility, so voglibose's relatively poor solubility has, to varying degrees, impacted its hypoglycemic efficacy. Furthermore, the API content in voglibose tablets is relatively small, making it a small-scale preparation. Therefore, content uniformity is a high-risk quality attribute requiring focused scrutiny. Although the methods for preparing voglibose tablets disclosed in existing patents have proposed solutions to the above problems, they still have certain shortcomings. For example, Chinese patent CN103006597B discloses a method for preparing voglibose, which uses an additive mixing method to meet the content uniformity test requirements, resulting in a cumbersome and complex operation process. Chinese patents CN108309946A and CN110101671A both disclose methods for preparing voglibose tablets, but use multiple instruments and equipment for premixing, soft material preparation, granulation, drying, and other operations. The preparation process is cumbersome, resulting in significant material loss and high labor intensity for workers. Chinese patents CN115737580A and CN114796136A both disclose methods for preparing voglibose tablets, both of which use a fluidized bed to prepare voglibose solid dispersions or granules. However, the excessive number and amount of excipients used significantly increases production costs and the risk of adverse reactions. In summary, the above methods are difficult to facilitate large-scale production of safe, effective and low-cost voglibose tablets for enterprises.

[0004] [Summary of the invention]

[0005] In view of the deficiencies of the prior art, the object of the present invention is to provide a voglibose tablet and a preparation method thereof that can be operated continuously, has low cost, high yield, is suitable for large-scale production, and has good dissolution and content uniformity.

[0006] The present invention simplifies the types of excipients through prescription screening and sets a high-quality ratio; the method of adding the raw material drug is investigated, and finally the raw material drug is dissolved in a binder solution and sprayed for addition is selected, which solves the problem of content uniformity of small-scale preparations after testing; a high-shear wet granulation process and a fluidized bed granulation process are studied, and a fluidized bed granulation process capable of continuous operation is adopted; the fluidized bed process parameters are studied, and a reasonable process parameter range is obtained. After testing, the prepared tablets have good content uniformity and high dissolution, thereby improving the drug utilization rate and better exerting the blood sugar-lowering effect of voglibose.

[0007] Specifically, the technical objective of the present invention is achieved through the following technical solution: a voglibose tablet, which comprises the following raw materials in parts by weight: 1 part of voglibose, 500-540 parts of lactose, 20-35 parts of hydroxypropyl cellulose, 1-3 parts of magnesium stearate, and 110-130 parts of corn starch.

[0008] Furthermore, the voglibose tablets include the following raw materials in parts by weight: 1 part of voglibose, 520 parts of lactose, 27 parts of hydroxypropyl cellulose, 2 parts of magnesium stearate, and 117 parts of corn starch.

[0009] Furthermore, a method for preparing voglibose tablets is as follows:

[0010] 1) Slurry preparation: Slowly add the adhesive hydroxypropyl cellulose into purified water at 60-80°C to prepare an adhesive solution with a solid content of 6%. Stirring is started. After the adhesive swells, dissolves and defoams, the raw material voglibose is added and dissolved. The solution is set aside.

[0011] 2) Pretreatment: Transfer the weighed added materials lactose and corn starch to a granulator for sieving. Select a sieve with a mesh size of 0.8 mm and control the speed to 750-1000 rpm.

[0012] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 60~80℃; when the material temperature rises to 28~43℃, open the air volume 20~80m 3 / h, fan frequency 40Hz, inlet air temperature 70℃, at the same time start the peristaltic pump speed 9~16rpm, spray gun atomization pressure 0.6~1.4Bar, control the inlet air humidity 6~9g / m 3 , spray the prepared adhesive and raw material drug solution in step 1) continuously; after the solution is completely sprayed, open the air volume 50-80m 3 / h, fan frequency 40Hz, inlet air temperature 70℃ for drying, when the moisture content is controlled at 1% to 3%, dry particles are discharged;

[0013] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation, with a sieve size of 0.8 mm and a rotation speed of 1500 rpm;

[0014] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0015] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets with a hardness of 6kg to 9kg.

[0016] The present invention has the following advantages:

[0017] The present invention simplifies the types of excipients through prescription screening and sets a high-quality ratio. The method of adding the API was investigated, ultimately choosing to dissolve the API in a binder solution and spray-add it. This method, after testing, solved the problem of content uniformity in small-scale preparations. High-shear wet granulation and fluidized bed granulation processes were studied, and a fluidized bed granulation process capable of continuous operation was adopted. Fluidized bed process parameters were studied, and a reasonable process parameter range was determined. The resulting tablets exhibited good content uniformity and high dissolution, improving drug utilization and better exerting the hypoglycemic efficacy of voglibose. Compared with the prior art, the present invention solves the problems of excessive excipient types, cumbersome operation, low yield, and poor dissolution and content uniformity during the preparation of voglibose tablets. This invention provides a voglibose tablet and preparation method that are simple to operate, suitable for industrial production, low cost, high yield, and good dissolution and content uniformity.

Brief Description of the Drawings

[0018] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0019] FIG1 is a process flow chart of a method for preparing voglibose tablets according to the present invention. [Specific implementation method]

[0020] The invention relates to a voglibose tablet, which comprises the following raw materials in parts by weight: 1 part of voglibose, 500-540 parts of lactose, 20-35 parts of hydroxypropyl cellulose, 1-3 parts of magnesium stearate, and 110-130 parts of corn starch.

[0021] Preferably, the voglibose tablets comprise the following raw materials in parts by weight: 1 part of voglibose, 520 parts of lactose, 27 parts of hydroxypropyl cellulose, 2 parts of magnesium stearate, and 117 parts of corn starch.

[0022] Referring to FIG1 , the present invention also relates to a method for preparing the above-mentioned voglibose tablet, which is specifically as follows:

[0023] 1) Slurry preparation: Slowly add the adhesive hydroxypropyl cellulose into purified water at 60-80°C to prepare an adhesive solution with a solid content of 6%. Stirring is started. After the adhesive swells, dissolves and defoams, the raw material voglibose is added and dissolved. The solution is set aside.

[0024] 2) Pretreatment: Transfer the weighed added materials lactose and corn starch to a granulator for sieving. Select a sieve with a mesh size of 0.8 mm and control the speed to 750-1000 rpm.

[0025] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 60~80℃; when the material temperature rises to 28~43℃, open the air volume 20~80m 3 / h, fan frequency 40Hz, inlet air temperature 60~80℃, at the same time, start the peristaltic pump speed 9~16rpm, spray gun atomization pressure 0.6~1.4Bar, control the inlet air humidity 6~9g / m 3 , spray the prepared adhesive and raw material drug solution in step 1) continuously; after the solution is completely sprayed, open the air volume 50-80m 3 / h, fan frequency 40Hz, inlet air temperature 70℃ for drying, when the moisture content is controlled at 1% to 3%, dry particles are discharged;

[0026] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation, with a sieve size of 0.8 mm and a rotation speed of 1500 rpm;

[0027] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0028] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets with a hardness of 6kg to 9kg.

[0029] The technical solution of the present invention will be clearly and completely described below in conjunction with Figure 1 and the specific embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work are within the scope of protection of the present invention. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are used. Reagents or instruments used where the manufacturer is not specified are conventional products that can be purchased commercially.

[0030] Example 1: Preparation of Voglibose Tablets

[0031] A voglibose tablet, the prescription composition of which is as follows:

[0032] Preparation process:

[0033] 1) Slurry preparation: Slowly add the binder hydroxypropyl cellulose into 70° C. purified water to prepare a binder solution with a solid content of 6%. Start stirring. After the binder swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside.

[0034] 2) Pretreatment: The weighed added materials lactose and corn starch were transferred to a granulator for sieving. The sieve size was 0.8 mm and the rotation speed was 1000 rpm.

[0035] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 70℃; when the material temperature rises to 28-30℃, gradually increase the air volume to 80m 3 / h, fan frequency 40Hz, air inlet temperature 70℃, peristaltic pump speed 12rpm, spray gun atomization pressure 1.0Bar, air inlet humidity 5.4g / m 3 , spray the adhesive prepared in step 1 and the raw material drug solution continuously; after the solution is completely sprayed, open the air volume 75m 3 / h, fan frequency 40Hz, inlet air temperature 65℃ for drying, and when the moisture content of the particles is controlled at 1.0% to 3.0%, dry particles are obtained when the material is discharged.

[0036] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation. A sieve with an aperture of 0.8 mm was selected and the rotation speed was controlled at 1500 rpm.

[0037] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0038] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0039] Example 2: Preparation of Voglibose Tablets

[0040] A voglibose tablet, the prescription composition of which is as follows:

[0041] Preparation process:

[0042] 1) Slurry preparation: Slowly add the binder hydroxypropyl cellulose into 70° C. purified water to prepare a binder solution with a solid content of 6%. Start stirring. After the binder swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside.

[0043] 2) Pretreatment: The weighed added materials lactose and corn starch were transferred to a granulator for sieving. The sieve size was 0.8 mm and the rotation speed was 1000 rpm.

[0044] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 70℃; when the material temperature rises to 28-30℃, gradually increase the air volume to 80m 3 / h, fan frequency 40Hz, inlet air temperature 70℃, peristaltic pump speed 12rpm, spray gun atomization pressure 1.0Bar, inlet air humidity 5.7g / m 3 , spray the adhesive prepared in step 1 and the raw material drug solution continuously; after the solution is completely sprayed, open the air volume 75m 3 / h, fan frequency 40Hz, inlet air temperature 65℃ for drying, and when the moisture content of the particles is controlled at 1.0% to 3.0%, dry particles are obtained when the material is discharged.

[0045] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation. A sieve with an aperture of 0.8 mm was selected and the rotation speed was controlled at 1500 rpm.

[0046] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0047] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0048] Example 3: Preparation of Voglibose Tablets

[0049] A voglibose tablet, the prescription composition of which is as follows:

[0050] Preparation process:

[0051] 1) Slurry preparation: slowly add part of the adhesive hydroxypropyl cellulose into 70° C. purified water to prepare an adhesive solution with a solid content of 8%. Start stirring. After the adhesive swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside.

[0052] 2) Pretreatment: The weighed added materials lactose, corn starch, and part of hydroxypropyl cellulose were transferred to a granulator for sieving. The sieve size was 0.8 mm and the rotation speed was 1000 rpm.

[0053] 3) Premixing: Place lactose and corn starch into a wet granulator, set the stirring speed to 400 rpm and the shear speed to 500 rpm, and mix for 300 seconds.

[0054] 4) Preparation of soft material: The stirring speed of the wet granulator was adjusted to 350 rpm and the shear speed was 800 rpm. The binder and the API solution prepared in step 1 were continuously atomized at an atomization pressure of 0.1 MPa and a spraying time of 143 s.

[0055] 5) Granulation: After the solution was added, the stirring speed of the wet granulator was adjusted to 250 rpm, the shear speed was 1000 rpm, and the granulation time was 120 s.

[0056] 6) Wet granulation: The soft material is transferred into the granulator for wet granulation, the sieve aperture is selected to be 4 mm, and the speed is controlled to be 1000 rpm.

[0057] 7) Drying: The wet granules are transferred into an oven for drying at an inlet air temperature of 70°C and a drying loss of 1.0% to 3.0%.

[0058] 8) Dry granulation: The dry granules were transferred to a granulator for dry granulation. The sieve size was selected to be 1.0 mm and the rotation speed was controlled to be 1000 rpm.

[0059] 9) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 15 rpm and the mixing time was 300 seconds. The mixed granules were discharged;

[0060] 10) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0061] Example 4: Preparation of Voglibose Tablets

[0062] A voglibose tablet, the prescription composition of which is as follows:

[0063] Preparation process:

[0064] 1) Preparation of slurry: Add the raw material voglibose into purified water and dissolve it for later use.

[0065] 2) Pretreatment: The weighed added materials lactose, corn starch, and hydroxypropyl cellulose were transferred to a granulator for sieving. The sieve size was 0.8 mm and the rotation speed was 1000 rpm.

[0066] 3) Premixing: Place lactose, corn starch and hydroxypropyl cellulose into a wet granulator, start stirring at 400 rpm and shearing at 500 rpm, and mix for 300 seconds.

[0067] 4) Preparation of soft material: The stirring speed of the wet granulator was adjusted to 350 rpm and the shear speed was 800 rpm. The API solution in step 1 was continuously atomized and added at an atomization pressure of 0.1 MPa and a spraying time of 143 s.

[0068] 5) Granulation: After the solution was added, the stirring speed of the wet granulator was adjusted to 250 rpm, the shear speed was 1000 rpm, and the granulation time was 120 s.

[0069] 6) Wet granulation: The soft material is transferred into the granulator for wet granulation, the sieve aperture is selected to be 4 mm, and the speed is controlled to be 1000 rpm.

[0070] 7) Drying: The wet granules are transferred into an oven for drying at an inlet air temperature of 70°C and a drying loss of 1.0% to 3.0%.

[0071] 8) Dry granulation: The dry granules were transferred to a granulator for dry granulation. The sieve size was selected to be 1.0 mm and the rotation speed was controlled to be 1000 rpm.

[0072] 9) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 15 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0073] 10) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0074] Example 5: Preparation of Voglibose Tablets

[0075] A voglibose tablet, the prescription composition of which is as follows:

[0076] Preparation process:

[0077] 1) Slurry preparation: Slowly add the binder hydroxypropyl cellulose into 70° C. purified water to prepare a binder solution with a solid content of 6%. Start stirring. After the binder swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside.

[0078] 2) Pretreatment: The weighed added materials lactose and corn starch were transferred to a granulator for sieving. The sieve size was 0.8 mm and the rotation speed was 1000 rpm.

[0079] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 60℃; when the material temperature rises to 25℃, gradually increase the air volume to 60m 3 / h, fan frequency 40Hz, inlet air temperature 60℃, at the same time, start the peristaltic pump, the speed is gradually adjusted from 9.5rpm to 11.5rpm, the spray gun atomization pressure is 0.6Bar, and the inlet air humidity is 8.5g / m 3 , spray the adhesive prepared in step 1 and the raw material drug solution continuously; after the solution is completely sprayed, open the air volume 65m 3 / h, fan frequency 40Hz, inlet air temperature 60℃ for drying, and dry particles are obtained when the moisture content of the particles is controlled at 1.0% to 3.0%.

[0080] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation. A sieve with an aperture of 0.8 mm was selected and the rotation speed was controlled at 1500 rpm.

[0081] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0082] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0083] Example 6: Preparation of Voglibose Tablets

[0084] A voglibose tablet, the prescription composition of which is as follows:

[0085] Preparation process:

[0086] 1) Slurry preparation: Slowly add the binder hydroxypropyl cellulose into 70° C. purified water to prepare a binder solution with a solid content of 6%. Start stirring. After the binder swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside.

[0087] 2) Pretreatment: The weighed added materials lactose and corn starch were transferred to a granulator for sieving. The sieve size was 0.8 mm and the rotation speed was 1000 rpm.

[0088] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 70℃; when the material temperature rises to 28℃, gradually increase the air volume to 70m 3 / h, fan frequency 40Hz, inlet air temperature 70℃, at the same time, start the peristaltic pump, speed gradually adjusted from 11.5rpm to 14.5rpm, spray gun atomization pressure 1.0Bar, inlet air humidity 8.1g / m 3 , spray the adhesive prepared in step 1 and the raw material drug solution continuously; after the solution is completely sprayed, open the air volume 70m 3 / h, fan frequency 40Hz, inlet air temperature 70℃ for drying, and when the moisture content of the particles is controlled at 1.0% to 3.0%, dry particles are obtained when the material is discharged.

[0089] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation. A sieve with an aperture of 0.8 mm was selected and the rotation speed was controlled at 1500 rpm.

[0090] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0091] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0092] Example 7: Preparation of Voglibose Tablets

[0093] A voglibose tablet, the prescription composition of which is as follows:

[0094] Preparation process:

[0095] 1) Slurry preparation: Slowly add the binder hydroxypropyl cellulose into 70° C. purified water to prepare a binder solution with a solid content of 6%. Start stirring. After the binder swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside.

[0096] 2) Pretreatment: The weighed added materials lactose and corn starch were transferred to a granulator for sieving. The sieve size was 0.8 mm and the rotation speed was 1000 rpm.

[0097] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 80℃; when the material temperature rises to 30℃, gradually increase the air volume to 65m 3 / h, fan frequency 40Hz, inlet air temperature 80℃, at the same time, start the peristaltic pump, speed gradually adjusted from 8.0rpm to 17rpm, spray gun atomization pressure 1.4Bar, inlet air humidity 8.9g / m 3 , spray the adhesive prepared in step 1 and the raw material drug solution continuously; after the solution is completely sprayed, open the air volume 65m 3 / h, fan frequency 40Hz, inlet air temperature 80℃ for drying, and when the moisture content of the particles is controlled at 1.0% to 3.0%, dry particles are obtained when the material is discharged.

[0098] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation. A sieve with an aperture of 0.8 mm was selected and the rotation speed was controlled at 1500 rpm.

[0099] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0100] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0101] Example 8: Preparation of Voglibose Tablets

[0102] A voglibose tablet, the prescription composition of which is as follows:

[0103] Production: 4000 pieces

[0104] Preparation process:

[0105] 1) Slurry preparation: Slowly add the binder hydroxypropyl cellulose into 70° C. purified water to prepare a binder solution with a solid content of 6%. Start stirring. After the binder swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside.

[0106] 2) Pretreatment: The weighed added materials lactose and corn starch were transferred to a granulator for sieving. The sieve size was 0.8 mm and the rotation speed was 1000 rpm.

[0107] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 70℃; when the material temperature rises to 28℃, gradually increase the air volume to 78m 3 / h, fan frequency 40Hz, inlet air temperature 70℃, peristaltic pump speed 16rpm, spray gun atomization pressure 1.0Bar, inlet air humidity 8.0g / m 3 , spray the adhesive prepared in step 1 and the raw material drug solution continuously; after the solution is completely sprayed, open the air volume 50m 3 / h, fan frequency 40Hz, inlet air temperature 70℃ for drying, and dry particles are obtained when the moisture content of the particles is controlled at 1.0% to 3.0%.

[0108] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation. A sieve with a mesh size of 0.6 mm was selected and the rotation speed was controlled at 1500 rpm.

[0109] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0110] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0111] Example 9: Preparation of Voglibose Tablets

[0112] A voglibose tablet, the prescription composition of which is as follows:

[0113] Production: 4000 pieces

[0114] Preparation process:

[0115] 1) Slurry preparation: Slowly add the binder hydroxypropyl cellulose into 70° C. purified water to prepare a binder solution with a solid content of 6%. Start stirring. After the binder swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside.

[0116] 2) Pretreatment: The weighed added materials lactose and corn starch are transferred to a granulator for sieving. The sieve size is 0.8 mm and the rotation speed is 1000 rpm.

[0117] 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 70℃; when the material temperature rises to 28℃, gradually increase the air volume to 78m 3 / h, fan frequency 40Hz, air inlet temperature 70℃, peristaltic pump speed 16rpm, spray gun atomization pressure 1.0Bar, air inlet humidity 8.0g / m 3 , spray the adhesive prepared in step 1 and the raw material drug solution continuously; after the solution is completely sprayed, open the air volume 50m 3 / h, fan frequency 40Hz, inlet air temperature 70℃ for drying, and when the moisture content of the particles is controlled at 1.0% to 3.0%, dry particles are obtained when the material is discharged.

[0118] 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation. A sieve with an aperture of 0.8 mm was selected and the rotation speed was controlled at 1500 rpm.

[0119] 5) Total mixing: The added material magnesium stearate was passed through a 60-mesh stainless steel sieve and transferred together with the granulated granules into a mixing hopper. The hopper mixer speed was set to 25 rpm and the mixing time was 300 seconds. The mixed granules were discharged.

[0120] 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets.

[0121] The voglibose wet granules prepared in Examples 3 and 4 of the present invention were subjected to a content uniformity test according to the Technical Guidelines for the Study of Mixing Uniformity and Controlled Dosage Unit Uniformity of Chemical Oral Solid Preparations (Trial Implementation). The results are shown in Table 1.

[0122] Table 1: Wet Granule Content Uniformity Results

[0123] In vitro dissolution curves of the voglibose tablets prepared in Examples 1 to 9 of the present invention and the original voglibose tablets were measured.

[0124] Chromatographic conditions: Based on the chromatographic conditions under the related substances of voglibose in Part II of the "Chinese Pharmacopoeia (2020 Edition)".

[0125] Determination method: According to the second method of Part 0931 of the fourth general rule of the "Chinese Pharmacopoeia (2020 Edition)", 900 mL of pH 1.2 hydrochloric acid solution was used as the dissolution medium, the rotation speed was 50 revolutions per minute, and the operation was carried out in accordance with the law. After 5, 10, 15, 20 and 30 minutes, an appropriate amount of solution was taken, filtered through a 0.45 μm filter membrane, and 0.3 mL of the subsequent filtrate was added to 0.7 mL of the mobile phase for dilution as the test solution; a reference solution with a concentration of approximately 0.1 μg / ml was prepared by taking a voglibose reference substance. Accurately measure 100 μL each of the reference solution and the test solution, inject them into the liquid chromatograph respectively, and record the chromatogram. The dissolution amount of each tablet was calculated by the external standard method.

[0126] Table 2: Dissolution curve of voglibose tablets in pH 1.2 medium

[0127] The above test results show that the dissolution of the voglibose tablets prepared in Examples 1-2 and Examples 5-9 using the fluidized bed granulation process is greater than 60, and the dissolution at 30 minutes is better than that of the original tablet, which can better exert the hypoglycemic effect of the voglibose tablets. The voglibose tablets prepared in Examples 3-4 using the high shear wet granulation method completely dissolve within 15 minutes, which is not similar to the dissolution of the original tablet, and the rapid dissolution is likely to cause gastric mucosal irritation. Therefore, the fluidized bed granulation is preferred in the present invention.

[0128] Compared with Example 2, Example 1 only changed the prescription ratio, but the dissolution of the voglibose tablets prepared in Example 1 was more similar to that of the original tablets, indicating that Example 1 is the preferred ratio;

[0129] The difference between Example 3 and Example 4 is that in the former, the API and hydroxypropyl cellulose are dissolved together to prepare a slurry, while in the latter, the API is dissolved in water and then added. The results show that both can be mixed evenly (the RSD of the particle content is less than 3.0%), and there is no significant difference in dissolution between the two. Therefore, the simpler former method can be selected.

[0130] Examples 5 to 7 investigated the range of fluidized bed process parameters. The results showed that the inlet air humidity was between 8 and 9 g / m 3 When the air inlet temperature is controlled at 60~80℃ and the air volume is controlled at 20~80m 3 / h, and atomization pressure range of 0.6-1.4Bar, the dissolution of the plain tablets in pH 1.2 medium had no significant difference from that of the original tablets, and the similarity factors f2 were greater than 60.

[0131] Examples 8-9 investigated the effect of sieve aperture during the dry granulation process on the dissolution of voglibose tablets. The results showed that when the sieve aperture of the dry granulation was in the range of 0.6-0.8 mm, there was no significant difference in the dissolution of the two batches of plain tablets, and the f2 fitting of the dissolution of the original tablets was greater than 70.

[0132] In summary, the present invention simplifies the types of excipients through prescription screening and sets a high-quality ratio. The method of adding the API was investigated, ultimately choosing to dissolve the API in a binder solution and spray-add it. This method, after testing, solved the problem of content uniformity in small-scale preparations. High-shear wet granulation and fluidized bed granulation processes were studied, and a fluidized bed granulation process capable of continuous operation was adopted. Fluidized bed process parameters were studied, and a reasonable process parameter range was obtained. The tablets produced after testing showed good content uniformity and high dissolution, thereby improving drug utilization and better exerting the hypoglycemic efficacy of voglibose. Compared with the prior art, the present invention solves the problems of excessive excipient types, cumbersome operation, low yield, and poor dissolution and content uniformity in the preparation of voglibose tablets. It provides a voglibose tablet and its preparation method that are simple to operate, suitable for industrial production, low cost, high yield, and good dissolution and content uniformity.

[0133] Although the specific embodiments of the present invention are described above, those skilled in the art should understand that the specific embodiments described are merely illustrative and are not intended to limit the scope of the present invention. Equivalent modifications and changes made by those skilled in the art in accordance with the spirit of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A voglibose tablet, characterized in that: The voglibose tablet comprises the following raw materials in parts by weight: 1 part of voglibose, 500-540 parts of lactose, 20-35 parts of hydroxypropyl cellulose, 1-3 parts of magnesium stearate, and 110-130 parts of corn starch.

2. A voglibose tablet according to claim 1, characterized in that: The voglibose tablet comprises the following raw materials in parts by weight: 1 part of voglibose, 520 parts of lactose, 27 parts of hydroxypropyl cellulose, 2 parts of magnesium stearate, and 117 parts of corn starch.

3. A method for preparing voglibose tablets, characterized in that: The voglibose tablet is based on the voglibose tablet according to claim 1, and the preparation method is as follows: 1) Slurry preparation: slowly add the adhesive hydroxypropyl cellulose into 60-80° C. purified water to prepare an adhesive solution with a solid content of 6%, start stirring, and after the adhesive swells, dissolves and defoams, add the raw material voglibose, dissolve it, and set aside; 2) Pretreatment: transfer the weighed added materials lactose and corn starch to the granulator for sieving, select the sieve mesh size of 0.8mm, and control the speed to 750-1000rpm; 3) Fluidized bed granulation: transfer the sieved lactose and corn starch into the fluidized bed granulator for premixing, and open the air volume to 20m 3 / h, fan frequency 40Hz, air inlet temperature 60~80℃; when the material temperature rises to 28~43℃, open the air volume 20~80m 3 / h, fan frequency 40Hz, inlet air temperature 60~80℃, peristaltic pump speed 9~16rpm, spray gun atomization pressure 0.6~1.4Bar, inlet air humidity 6~9g / m 3 , continuously spray the prepared adhesive and raw material drug solution in step 1); after the solution is completely sprayed in, open the air volume to 50-80m 3 / h, fan frequency 40Hz, inlet air temperature 70℃ for drying, when the moisture content is controlled at 1% to 3%, dry particles are obtained; 4) Dry granulation: The dry granules were transferred to a granulator for dry granulation, with a sieve aperture of 0.8 mm and a rotation speed of 1500 rpm; 5) Total mixing: the additional material magnesium stearate is passed through a 60-mesh stainless steel sieve and transferred to a mixing hopper together with the granulated particles. The hopper mixer speed is set to 25 rpm and the mixing time is 300 seconds. The total mixed particles are obtained by discharging the material; 6) Tableting: tabletting is performed using a tablet press to obtain voglibose tablets with a hardness of 6kg to 9kg.

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