CN118750458A - A preparation method of simvastatin tablets - Google Patents

Abstract

The present invention relates to a preparation method of simvastatin tablets, belonging to the technical field of pharmaceutical preparations. A preparation method of simvastatin tablets is provided, the method comprising ultrasonically grinding simvastatin to obtain simvastatin ultrafine powder, grinding the simvastatin ultrafine powder together with part of pregelatinized starch, sieving, adding the obtained grinding mixture and filler into a dry granulator for granulation through a 0.8mm screen to obtain simvastatin mixture particles, spray drying, mixing the obtained particles with pharmaceutical excipients, pressing into tablet cores, and film coating the obtained tablet cores to obtain simvastatin tablets; the present invention as a whole has the advantages of high drug quality and less loss of raw material micropowder.

Description

A preparation method of simvastatin tablets

Technical Field

The invention relates to a method for preparing a simvastatin tablet, and belongs to the field of preparation of drug tablets.

Background Art

Simvastatin is a lipid-lowering drug of the statin class, used to control the cholesterol content in the blood and prevent cardiovascular diseases. It can inhibit the synthesis of endogenous cholesterol and is a blood lipid regulator. It is clinically used to treat hypercholesterolemia and coronary heart disease.

In the preparation process of simvastatin tablets, the traditional method usually includes directly mixing the active ingredient with the excipients, and then completing it through steps such as boiling granulation and tableting. However, due to the need for heating, there may be certain restrictions on heat-sensitive substances, so the boiling granulation process may cause the stability of the active ingredient to decrease, affecting the quality of the drug; in addition, during the boiling process, micropowders may fly and cause raw material loss, requiring effective dust control equipment, which is not conducive to large-scale industrial production.

Summary of the invention

The present invention aims at the defects existing in the above prior art and provides a method for preparing simvastatin tablets, which solves the problem of improving the quality of the medicine and reducing the loss of raw material micro powder.

The object of the present invention is achieved by the following technical scheme: a method for preparing simvastatin tablets, the method comprising:

S1: subjecting simvastatin to ultrasonic grinding to obtain simvastatin ultrafine powder;

S2: pulverize simvastatin ultrafine powder and part of pregelatinized starch together and sieve;

S3: adding the crushed mixture obtained in step S2 together with the filler into a dry granulator for granulation through a 0.8 mm sieve to obtain simvastatin mixture particles, and spray drying;

S4: mixing the particles obtained in step S3 with pharmaceutical excipients and pressing them into tablet cores;

S5: Film-coating the tablet core obtained in step S4 to obtain simvastatin tablets.

Furthermore, in the step S1, an ultrasonic pulverizer is used to vibrate and pulverize simvastatin, and the specific surface area of the simvastatin ultrafine powder is 1900-2050 m2/kg.

Furthermore, in the step S2, a turbine self-cooling dust-free pulverizer is used for pulverization, and the mesh number of the sieve used for sieving is 144-225 meshes.

The pulverization can make the simvastatin ultrafine powder and the pregelatinized starch initially mixed, and at the same time play a simple mixing role, which is more conducive to the uniformity of the content of the particles.

Furthermore, in step S2, the simvastatin ultrafine powder and the partially pregelatinized starch are first mixed according to a continuous mixing method, with a raw material supply speed of 6-10 kg/min and a mixing speed of 50-200 r/min.

The supply and mixing of raw materials during the mixing process are carried out continuously, which is suitable for situations requiring large-scale production and continuous processing, and can achieve an efficient and continuous mixing process.

Furthermore, in step S3, the step of dry granulation comprises:

T1: The obtained pulverized mixture is mixed evenly with the filler in a ratio of 1:2-5, and after the mixing is completed, it is conveyed to the dry granulator;

T2: In the dry granulator, the raw materials are compressed into granules by mechanical pressure through equipment such as rotary granulators and extrusion granulators;

T3: magnesium stearate was added during granulation to improve the fluidity and formability of the granules;

T4: After granulation is completed, the granules are transported to a drying device for drying at a drying temperature of 45-55°C. The drying loss of the obtained granules is ≤5.0%.

Preferably, the crushed mixture and the filler are mixed in a ratio of 1:3.

Furthermore, in step S2, the filler is selected from one or more of sorbitol, maltose, lactose, cross-linked sodium carboxymethyl cellulose, microcrystalline cellulose, and starch acetate.

Furthermore, in the step S3, after the spray drying, the particles are also screened, the sized simvastatin mixture particles are sucked into a three-dimensional rotary vibrating screen through a vacuum feeder, a 20-mesh screen is used to remove coarse particles, a 60-mesh screen is used to remove fine particles, and the coarse particles are repeatedly sized to obtain heavy powder particles.

Furthermore, in step S3, the roller pressure of the dry granulator is 8-10 MPa, the roller gap is 0.6-0.9 mm, the roller speed is 15-20 r/min, and the three-element rotary vibrating screen speed is 100-120 r/min.

Furthermore, in step S4, the pharmaceutical excipients include one or more of stearate, silicon dioxide, maltose, calcium silicate and sodium carboxymethyl starch.

A simvastatin tablet comprises the following components and their weight ratios: 10-35 parts by weight of simvastatin, 10-15 parts by weight of partially pregelatinized starch, 20-75 parts by weight of a filler, 3-9 parts by weight of magnesium stearate and 10-18 parts by weight of a pharmaceutical excipient.

In summary, compared with the prior art, the present invention has the following advantages:

1. In the present invention, after simvastatin is micronized, the particle size and specific surface area are increased, and the contact area between the drug particles and the dissolution medium is increased. The increased contact area is conducive to faster and more complete dissolution of the drug particles in the dissolution medium, thereby improving the in vitro dissolution rate. The uniform particle size distribution helps the drug to dissolve uniformly in the dissolution medium, thereby improving the uniformity of the dissolution rate. The improvement of the in vitro dissolution rate and the improvement of the dissolution uniformity are conducive to faster and more uniform release and absorption of the drug in the body;

2. In the present invention, an ultrasonic pulverizer is used to vibrate and pulverize simvastatin to obtain simvastatin ultrafine powder with a large specific surface area, which is beneficial to improving the drug dissolution rate and bioavailability, thereby improving the therapeutic effect. A turbine self-cooling dust-free pulverizer is used to pulverize simvastatin ultrafine powder and pregelatinized starch, and the pulverized powder is passed through a 144-mesh sieve, thereby ensuring the fineness and uniformity of the raw materials, which is beneficial to improving the product quality.

3. In the present invention, part of the pregelatinized starch is sprayed in the dry preparation process, thereby avoiding the loss of raw materials caused by the flying of raw material powder.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a preparation flow chart of the present invention;

FIG. 2 is a dissolution comparison diagram of the present invention.

DETAILED DESCRIPTION

The technical solution of the present invention is further specifically described below through specific embodiments, but the present invention is not limited to these embodiments.

Prepare the raw materials according to the following amounts: 18 parts by weight of simvastatin, 12 parts by weight of partially pregelatinized starch, 54 parts by weight of filler (20 parts by weight of microcrystalline cellulose, 15 parts by weight of lactose, 19 parts by weight of cross-linked sodium carboxymethyl cellulose), 6 parts by weight of magnesium stearate, and 10 parts by weight of pharmaceutical excipients (5 parts by weight of sodium carboxymethyl starch, 2 parts by weight of magnesium stearate, 1 part by weight of maltose, and 2 parts by weight of calcium silicate).

(1) pulverizing simvastatin by vibration using an ultrasonic pulverizer to obtain simvastatin ultrafine powder with a specific surface area of 2050 m2/kg;

(2) The micronized simvastatin and pregelatinized starch were pulverized by a turbine self-cooling dust-free pulverizer and passed through a 144-mesh sieve after pulverization, wherein the ultrafine simvastatin powder and pregelatinized starch were first mixed according to a continuous mixing method and then pulverized, the raw material supply speed was 8 kg/min, and the mixing speed was 125 rpm/min;

(3) Then, the obtained pulverized mixture is mixed with microcrystalline cellulose, lactose, and cross-linked sodium carboxymethyl cellulose, and then a portion of pregelatinized starch is sprayed into the mixture, and then granulated in a dry granulator. The roller pressure of the dry granulator is 8-10 MPa, the roller gap is 0.6-0.9 mm, the roller speed is 15-20 r/min, and the three-element rotary vibrating screen speed is 100-120 r/min. Magnesium stearate is added during the granulation process to improve the fluidity and formability of the granules. After the granulation is completed, the granules are transported to a drying device for drying at a drying temperature of 45-55° C. The drying loss of the obtained granules is ≤5.0%. After the spray drying is completed, the obtained granules are sieved to obtain granules with a particle size of 60 mesh;

(4) Then, sodium carboxymethyl starch, magnesium stearate, maltose, and calcium silicate are added, mixed evenly, and the prepared granules are pressed into tablet cores;

(5) Finally, the obtained tablet cores are film-coated to obtain simvastatin tablets, and the weight of each simvastatin tablet obtained is about 0.12 g.

Prepare raw materials according to the following amounts: 35 parts by weight of simvastatin, 15 parts by weight of partially pregelatinized starch, 75 parts by weight of filler (35 parts by weight of microcrystalline cellulose, 18 parts by weight of lactose, 22 parts by weight of cross-linked sodium carboxymethyl cellulose), 9 parts by weight of magnesium stearate, and 18 parts by weight of pharmaceutical excipients (9 parts by weight of sodium starch glycolate, 3 parts by weight of magnesium stearate, 3 parts by weight of maltose, and 3 parts by weight of calcium silicate).

(1) pulverizing simvastatin by vibration using an ultrasonic pulverizer to obtain simvastatin ultrafine powder with a specific surface area of 2050 m2/kg;

(2) The micronized simvastatin and pregelatinized starch were pulverized by a turbine self-cooling dust-free pulverizer and passed through a 144-mesh sieve after pulverization, wherein the ultrafine simvastatin powder and pregelatinized starch were first mixed according to a continuous mixing method and then pulverized, the raw material supply speed was 8 kg/min, and the mixing speed was 125 rpm/min;

(3) Then, the obtained pulverized mixture is mixed with microcrystalline cellulose, lactose, and cross-linked sodium carboxymethyl cellulose, and then a portion of pregelatinized starch is sprayed into the mixture, and then granulated in a dry granulator. The roller pressure of the dry granulator is 8-10 MPa, the roller gap is 0.6-0.9 mm, the roller speed is 15-20 r/min, and the three-element rotary vibrating screen speed is 100-120 r/min. Magnesium stearate is added during the granulation process to improve the fluidity and formability of the granules. After the granulation is completed, the granules are transported to a drying device for drying at a drying temperature of 45-55° C. The drying loss of the obtained granules is ≤5.0%. After the spray drying is completed, the obtained granules are sieved to obtain granules with a particle size of 60 mesh;

(4) Then, sodium carboxymethyl starch, magnesium stearate, maltose, and calcium silicate are added, mixed evenly, and the prepared granules are pressed into tablet cores;

(5) Finally, the obtained tablet cores are film-coated to obtain simvastatin tablets, and the weight of each simvastatin tablet obtained is about 0.12 g.

Prepare the raw materials according to the following amounts: 10 parts by weight of simvastatin, 10 parts by weight of partially pregelatinized starch, 20 parts by weight of filler (10 parts by weight of microcrystalline cellulose, 4 parts by weight of lactose, 6 parts by weight of cross-linked sodium carboxymethyl cellulose), 3 parts by weight of magnesium stearate, and 10 parts by weight of pharmaceutical excipients (4 parts by weight of sodium carboxymethyl starch, 2 parts by weight of magnesium stearate, 1 part by weight of maltose, and 3 parts by weight of calcium silicate).

(1) pulverizing simvastatin by vibration using an ultrasonic pulverizer to obtain simvastatin ultrafine powder with a specific surface area of 2050 m2/kg;

(2) The micronized simvastatin and pregelatinized starch were pulverized by a turbine self-cooling dust-free pulverizer and passed through a 144-mesh sieve after pulverization, wherein the ultrafine simvastatin powder and pregelatinized starch were first mixed according to a continuous mixing method and then pulverized, the raw material supply speed was 8 kg/min, and the mixing speed was 125 rpm/min;

(3) Then, the obtained pulverized mixture is mixed with microcrystalline cellulose, lactose, and cross-linked sodium carboxymethyl cellulose, and then a portion of pregelatinized starch is sprayed into the mixture, and then granulated in a dry granulator. The roller pressure of the dry granulator is 8-10 MPa, the roller gap is 0.6-0.9 mm, the roller speed is 15-20 r/min, and the three-element rotary vibrating screen speed is 100-120 r/min. Magnesium stearate is added during the granulation process to improve the fluidity and formability of the granules. After the granulation is completed, the granules are transported to a drying device for drying at a drying temperature of 45-55° C. The drying loss of the obtained granules is ≤5.0%. After the spray drying is completed, the obtained granules are sieved to obtain granules with a particle size of 60 mesh;

(4) Then, sodium carboxymethyl starch, magnesium stearate, maltose, and calcium silicate are added, mixed evenly, and the prepared granules are pressed into tablet cores;

(5) Finally, the obtained tablet cores are film-coated to obtain simvastatin tablets, and the weight of each simvastatin tablet obtained is about 0.12 g.

The simvastatin tablets prepared in Examples 1, 2, and 3 of the present invention were compared with the related substances of simvastatin tablets sold on the market. The results are shown in the table in FIG.

The implementation of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the present invention, ordinary technicians in this field can make various changes and improvements to the present invention in form and detail, and these are considered to fall within the protection scope of the present invention.

Claims (10)

1. A process for the preparation of a simvastatin tablet comprising:

s1: carrying out ultrasonic grinding on the simvastatin to obtain simvastatin ultra-fine powder;

s2: grinding the simvastatin ultra-fine powder and part of pregelatinized starch together, and sieving;

S3: adding the crushed mixture obtained in the step S2 and a filler into a dry granulator together, granulating through a 0.8mm screen to obtain simvastatin mixture particles, and spray-drying;

s4: mixing the granules obtained in the step S3 with pharmaceutical excipients, and pressing into tablet cores;

s5: and (3) carrying out film coating on the tablet core obtained in the step (S4) to obtain the simvastatin tablet.

2. The method for preparing simvastatin tablet according to claim 1, characterized in that: in the step S1, the simvastatin is crushed by vibration by an ultrasonic crusher, and the specific surface area of the simvastatin ultra-fine powder is 1900-2050 m ²/kg.

3. The method for preparing simvastatin tablet according to claim 2, characterized in that: in the step S2, a turbine self-cooling dust-free pulverizer is adopted for pulverizing, and the number of the screen meshes used for sieving is 144-225 meshes.

4. A process for the preparation of a simvastatin tablet according to claim 3, characterized in that: in the step S2, the simvastatin ultra-fine powder and the part of pregelatinized starch are mixed according to a continuous mixing method, the raw material supply speed is 6-10 kg/min, and the mixing speed is 50-200 r/min.

5. The method for preparing simvastatin tablet according to claim 4, wherein: in the step S3, the step of dry granulation includes:

T1: the resulting pulverized mixture was mixed with filler at 1: 2-5, after mixing, conveying the mixture into a dry granulator;

T2: in a dry granulator, the raw materials are compressed into granules by using mechanical pressure through equipment such as a rotary granulator, an extrusion granulator and the like;

t3: magnesium stearate is added in the granulating process to improve the fluidity and formability of the granules;

t4: after the granulation is completed, the granules are conveyed into a drying device for drying, the drying temperature is 45-55 ℃, and the drying weight loss of the obtained granules is less than or equal to 5.0%.

6. The method for preparing simvastatin tablet according to claim 5, wherein: in the step S3, the filler is one or more selected from sorbitol, maltose, lactose, croscarmellose sodium, microcrystalline cellulose and starch acetate.

7. The method for preparing simvastatin tablet according to claim 6, characterized in that: in the step S3, the spray drying step further comprises the step of sieving the particles, sucking the prepared simvastatin mixture particles into a ternary rotary vibration sieve through a vacuum feeding machine, removing coarse particles through a 20-mesh sieve, removing fine particles through a 60-mesh sieve, and repeatedly carrying out coarse particle sizing to obtain heavy powder particles.

8. The method for preparing simvastatin tablet according to claim 7, characterized in that: in the step S3, the pressure of a compression roller of the dry granulator is 8-10 MPa, the clearance of the compression roller is 0.6-0.9 mm, the rotating speed of the compression roller is 15-20 r/min, and the rotating speed of the ternary rotary vibrating screen is 100-120 r/min.

9. The method for preparing simvastatin tablet according to claim 8, characterized in that: in the step S4, the pharmaceutical excipients include one or more of stearate, silicon dioxide, maltose, calcium silicate and carboxymethyl starch sodium.

10. The simvastatin tablet prepared by the preparation method according to claim 1 comprises the following components in parts by weight: 10-35 parts of simvastatin, 10-15 parts of partially pregelatinized starch, 20-75 parts of filler, 3-9 parts of magnesium stearate and 10-18 parts of pharmaceutical auxiliary materials.