CN105395499A - Stable mannose ester tablet and preparation method thereof - Google Patents

Abstract

The invention relates to a stable mannose ester tablet and a preparation method thereof, and belongs to the technical field of a pharmaceutical preparation. The mannose ester tablet consists of mannose ester and preparation adjuvant materials, wherein the preparation adjuvant materials include a filling agent, a disintegrating agent, a binding agent and a lubricating agent. The mannose ester tablet disclosed by the invention has the advantages of being stable in quality, rapid in disintegration and dissolution, rapid in absorption, high in bioavailability, moderate in hardness, good in stability, convenient to take, simple in preparation process and the like.

Description

A kind of stable glycose ester tablet and preparation method thereof

technical field

The invention relates to tablets, in particular to glycose ester tablets and a preparation method thereof.

Background technique

Glyceride is the sodium salt of polymannuronic acid propyl ester sulfate obtained by the hydrolysis and esterification of sodium alginate. It is a marine drug for lowering blood fat and antithrombotic, and is used for the treatment of hyperlipidemia. The tablet can cover the bad smell of the medicine and is easy to swallow; it can improve the stability and bioavailability of the medicine, can make up for the deficiency of other solid dosage forms, and is widely used. The existing glycose ester tablets have the defects of poor disintegration and dissolution effect and low bioavailability, which affect their clinical therapeutic effects. Therefore, it is necessary to develop glycose ester tablets with short disintegration time and rapid drug dissolution.

Contents of the invention

The object of the present invention is to provide a kind of glycose ester tablet with short disintegration time and rapid drug dissolution and its preparation method.

1. a stable glyceride tablet, is characterized in that, comprises glyceride, filler, disintegrant, binding agent and lubricant. Wherein, the filler is selected from the mixture of sucrose and pregelatinized starch, the disintegrant is selected from cross-linked carboxymethyl cellulose, and the binder is selected from 70% syrup; The agent is selected from magnesium stearate.

2. A stable glycose ester tablet according to claim 1, characterized in that: the glycose ester raw material contains at least 90% of particles with a particle size less than 10 μm.

3. a kind of stable sugar ester tablet according to claim 1, is characterized in that: the weight ratio of described filler pregelatinized starch and disintegrant cross-linked carboxymethyl cellulose is 1:1.

4. A kind of stable glycose ester tablet according to claim 1, is characterized in that: in every 1000 tablets of 50mg/tablet, the glycose ester 50g, sucrose 36g, pregelatinized starch 4.5g, Composition of 4.5g of carboxymethylcellulose, 30g of 70% syrup, 0.6g of magnesium stearate, and 3.33ml of ethanol.

5. the preparation method of a kind of stable glyceride sheet according to claim 4, is characterized in that: comprise the following steps:

(1) Pretreatment: Ultrafine pulverization of sugar ester raw materials by jet mill, the particle size D50 of raw materials after micronization is 1-10 μm, sucrose and cross-linked carboxymethyl cellulose meet the requirements of 40 meshes; starch, pregelatin Requirements for starch and magnesium stearate to pass through a 80-mesh sieve;

(2) Total blending: after the glycerin ester and sucrose are mixed, magnesium stearate is added to increase the fluidity, mixed, and then other excipients are added, mixed;

(3) Tablet pressing: The temperature between tablet pressing is 18-26°C, and the relative humidity is controlled at 45-65%.

The present invention can be prepared as follows:

(1) Use a jet mill to ultrafinely pulverize the sugar ester raw material, the particle size D50 of the raw material after micronization is 1-10 μm, sucrose and cross-linked carboxymethyl cellulose are pulverized and passed through a 40-mesh sieve, starch, pregelatinized Starch and magnesium stearate are pulverized and passed through an 80-mesh sieve for subsequent use;

(2) Mixing granulation: Put the weighed glyceride raw material, sucrose powder, starch and 1/2 pregelatinized starch into the wet mixing granulator, dry mix for about 5 minutes, add the prescription amount of syrup and wet mix , When the material is slightly lumpy, stop the machine and discharge the material, and use a 16-mesh nylon screen to granulate;

(3) Drying: Put the wet granules in a drying tray, the thickness is generally 2.5cm, and send them into an oven at a temperature of 60-75°C to control the drying weight loss to ≤9.0%. After drying, the granules are allowed to cool to room temperature and discharged;

(4) Grain sizing: the dried granules are sieved with a 14-mesh nylon screen;

(5) Total blending: Put the granular materials into a three-dimensional motion mixer, add the remaining 1/2 pregelatinized starch and magnesium stearate, mix for 10 minutes, and discharge;

(6) Compression, coating, aluminum-plastic packaging.

detailed description

The present invention will be further described below in conjunction with specific embodiments, and the advantages and characteristics of the present invention will become clearer along with the description. However, these embodiments are only exemplary and do not constitute any limitation to the scope of the present invention. Those skilled in the art should understand that the details and forms of the technical solutions of the present invention can be modified or replaced without departing from the spirit and scope of the present invention, but these modifications and replacements all fall within the protection scope of the present invention.

The above-mentioned content of the present invention will be described in further detail below through the embodiment form, but this should not be interpreted as the scope of the above-mentioned theme of the present invention being limited to the following examples, and all technologies realized based on the above-mentioned content of the present invention all belong to the present invention range.

Example 1

Prescription 1 (according to 1000 tablets)

Glycerides (dried and pure) 50g

Sucrose 36g

Pregelatinized starch 4.5g

Croscarmellose 4.5g

Magnesium stearate 0.6g

70% syrup about 30g

Ethanol 3.33ml

Preparation:

(1) Use a jet mill to ultrafinely pulverize the sugar ester raw material, the particle size D50 of the raw material after micronization is 1-10 μm, sucrose and cross-linked carboxymethyl cellulose are pulverized and passed through a 40-mesh sieve, starch, pregelatinized Starch and magnesium stearate are pulverized and passed through an 80-mesh sieve for subsequent use;

(2) Mixing granulation: Put the weighed glyceride raw material, sucrose powder, starch and 1/2 pregelatinized starch into the wet mixing granulator, dry mix for about 5 minutes, add the prescription amount of syrup and wet mix , When the material is slightly lumpy, stop the machine and discharge the material, and use a 16-mesh nylon screen to granulate;

(3) Drying: Put the wet granules in a drying tray, the thickness is generally 2.5cm, and send them into an oven at a temperature of 60-75°C to control the drying weight loss to ≤9.0%. After drying, the granules are allowed to cool to room temperature and discharged;

(4) Grain sizing: the dried granules are sieved with a 14-mesh nylon screen;

(5) Total blending: Put the granular materials into a three-dimensional motion mixer, add the remaining 1/2 pregelatinized starch and magnesium stearate, mix for 10 minutes, and discharge;

(6) Compression, coating, aluminum-plastic packaging.

Example 2

Prescription 2 (according to 1000 tablets)

Glycerides (dried and pure) 50g

Sucrose 32g

Pregelatinized starch 4.0g

Croscarmellose 4.0g

Magnesium stearate 0.6g

70% syrup about 30g

Ethanol 3.33ml

The preparation method is the same as in Example 1.

Example 3

Prescription 3 (according to 1000 tablets)

Glycerides (dried and pure) 50g

Sucrose 30g

Pregelatinized starch 5.0g

Croscarmellose 5.0g

Magnesium stearate 0.6g

70% syrup about 30g

Ethanol 3.33ml

The preparation method is the same as in Example 1.

Comparative Example 1

Prescription 4 (according to 1000 tablets)

Glycerides (dried and pure) 50g

Sucrose 36g

Croscarmellose 4.5g

Magnesium stearate 0.6g

70% syrup about 30g

Ethanol 3.33ml

The preparation method is the same as in Example 1.

Comparative Example 2

Prescription 5 (according to 1000 tablets)

Glycerides (dried and pure) 50g

Pregelatinized starch 4.5g

Croscarmellose 4.5g

Magnesium stearate 0.6g

70% syrup about 30g

Ethanol 3.33ml

The preparation method is the same as in Example 1.

Test example 1 long-term stability test content determination

The samples to be marketed are placed at a temperature of 25°C and a relative humidity of 60% for 36 months, and samples are taken at 0, 3, 6, 12, 24, and 36 months respectively, and high-performance liquid chromatography ("Chinese Pharmacopoeia" 2015 edition four volumes) General rule 0512) for determination, using external standard method to calculate the content, the content determination results are shown in Table 1. The results show that the stability of the active ingredient glycose ester in the glycose ester tablet of the present invention is obviously better than that of the comparative examples.

Test Example 2 Bioavailability Test

Oral administration is carried out to 4 beagle dogs (all are male), they are respectively fed with the glycose ester sheet of the embodiment of the present invention 1, comparative example 1, comparative example 2 (temperature 25 ℃, relative humidity 60% 12 months), the dosage is 10.0μg/monkey (calculated as glyceride), and the interval between each administration is 7 days. After drug administration, blood samples were collected at different times, and the maximum blood concentration (C _max ) and bioavailability (AUC _0→48 ) of glycerides were calculated. The collection time points are 0h, 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h, 24h, 32h, 48h.

Table 2 provides the average results obtained by administering the glycose ester tablets of Example 1, Comparative Example 1, and Comparative Example 2 of the present invention to 4 Beagle dogs. It can be seen from the table that the maximum blood concentration and bioavailability of the glycose ester tablet of the present invention (Example 1) are significantly higher than those of the comparative example.

It should be noted that the above descriptions are only preferred embodiments of the present invention, and are not intended to limit the scope of the present invention. Any modifications, equivalent replacements and improvements made within the spirit and principles of the present invention , should be included within the protection scope of the present invention.

The mensuration of test example 3 dissolution rate

According to the dissolution and release test method (the second method of 0931 of the fourth general rule of "Chinese Pharmacopoeia" 2015 edition). Take each 6 pieces of glycose ester tablets of the present invention, use pH 1.2 hydrochloric acid and water as solvents respectively, and the rotating speed is 75 rpm, operate according to the law, take an appropriate amount of solution and filter in 5, 10, 15, 30, 45 minutes respectively, As the test solution; in addition, accurately weigh about 25mg of the reference substance glycose ester, put it in a 25ml measuring bottle, add a proper amount of acetonitrile to sonicate to dissolve, dilute to the mark, and shake well. Precisely measure 1ml and put it in a 100ml measuring bottle, add dissolution medium to dilute to the mark, shake well, and use it as the reference substance solution. Take the test solution and the reference solution respectively, and calculate the dissolution rate according to the ultraviolet-visible spectrophotometry ("Chinese Pharmacopoeia" 2015 edition four general rules 0401), the results are shown in Table 3 and Table 4:

It can be seen that the sugar ester tablets prepared by the method of the present invention have uniform dissolution in pH 1.2 hydrochloric acid and water, and can reach a higher dissolution rate in the 45th minute, which is obviously better than that of the comparative examples. It shows that the glycose ester tablet of the present invention has the advantages of stable quality, rapid disintegration and dissolution, fast absorption, high bioavailability, moderate hardness, good stability, convenient administration, and simple preparation process. At the same time, the preparation method in the method of the present invention is suitable for scaled-up production.

Claims (6)

1. a stable glycose ester tablet, is characterized in that, comprises glycose ester, filler, disintegrant, binding agent and lubricant; Wherein, described filler is selected from sucrose and pregelatinized starch Mixture, described disintegrant is selected from cross-linked carboxymethyl cellulose, and described binding agent is selected from 70% syrup; Described lubricant is selected from magnesium stearate. 2. A stable glycose ester tablet according to claim 1, characterized in that: the glycose ester raw material contains at least 90% of particles with a particle size less than 10 μm. 3. a kind of stable sugar ester tablet according to claim 1, is characterized in that: the weight ratio of described filler pregelatinized starch and disintegrant cross-linked carboxymethyl cellulose is 1:1. 4. A kind of stable glycose ester tablet according to claim 1, is characterized in that: in every 1000 tablets of 50mg/tablet, the glycose ester 50g, sucrose 36g, pregelatinized starch 4.5g, Composition of 4.5g of carboxymethylcellulose, 30g of 70% syrup, 0.6g of magnesium stearate, and 3.33ml of ethanol. 5. the preparation method of a kind of stable glyceride sheet according to claim 4, is characterized in that: comprise the following steps: (1) Pretreatment: Ultrafine pulverization of sugar ester raw materials by jet mill, the particle size D50 of raw materials after micronization is 1-10 μm, sucrose and cross-linked carboxymethyl cellulose meet the requirements of 40 meshes; starch, pregelatin Requirements for starch and magnesium stearate to pass through a 80-mesh sieve; (2) Total blending: after the glycerin ester and sucrose are mixed, magnesium stearate is added to increase the fluidity, mixed, and then other excipients are added, mixed; (3) Tablet pressing: The temperature between tablet pressing is 18-26°C, and the relative humidity is controlled at 45-65%. 6. A preparation method of glycose ester sheet, characterized in that it is realized through the following steps: (1) Use a jet mill to ultrafinely pulverize the sugar ester raw material, the particle size D50 of the raw material after micronization is 1-10 μm, sucrose and cross-linked carboxymethyl cellulose are pulverized and passed through a 40-mesh sieve, starch, pregelatinized Starch and magnesium stearate are pulverized and passed through an 80-mesh sieve for subsequent use; (2) Mixing granulation: Put the weighed glyceride raw material, sucrose powder, starch and 1/2 pregelatinized starch into the wet mixing granulator, dry mix for about 5 minutes, add the prescription amount of syrup and wet mix , When the material is slightly lumpy, stop the machine and discharge, and use a 16-mesh nylon screen to granulate; (3) Drying: Put the wet granules in a drying tray, the thickness is generally 2.5cm, and send them into an oven at a temperature of 60-75°C Drying, control drying weight loss ≤ 9.0%; after drying, dry the particles to room temperature and discharge; (4) Grain sizing: the dried granules are sieved with a 14-mesh nylon screen; (5) Total blending: Put the granular materials into a three-dimensional motion mixer, add the remaining 1/2 pregelatinized starch and magnesium stearate, mix for 10 minutes, and discharge; (6) Compression, coating, aluminum-plastic packaging.