Dexamethasone acetate tablet and preparation method thereof

Abstract

The invention provides a dexamethasone acetate tablet and a preparation method thereof, and relates to the technical field of preparation of dexamethasone acetate tablets. The dexamethasone acetate tablet is prepared from dexamethasone acetate, corn starch, sucrose fatty acid ester, modified microcrystalline cellulose, sucrose, sorbitol, carboxymethyl starch sodium, magnesium stearate and lauryl sodium sulfate, wherein the modified microcrystalline cellulose is obtained by adding water into microcrystalline cellulose and pregelatinized starch, mixing, fully shearing and stirring, and performing high-pressure treatment. According to the dexamethasone acetate tablet, the defects in the prior art are overcome, a large amount of dexamethasone acetate can be rapidly disintegrated and dissolved in a short time, long-time dissolution of subsequent drugs is also ensured, and early rapid disintegration and subsequent slow release of the tablet are realized.

Description

Technical Field

[0001] The invention relates to the technical field of preparation of dexamethasone acetate tablets, and in particular to a dexamethasone acetate tablet and a preparation method thereof. Background Art

[0002] Dexamethasone acetate is a common adrenal cortex hormone drug that can effectively treat rheumatoid arthritis and has anti-allergic and anti-inflammatory effects. After taking the drug, it is used to treat allergic and autoimmune inflammatory diseases, such as dermatitis, ulcerative colitis and other diseases, and can also reduce the body's ability to bind to cells to achieve an anti-infection effect.

[0003] Generally, dexamethasone acetate is prepared into tablets or injections. Since dexamethasone acetate is mostly used for symptoms such as acute allergies and asthma, in order to quickly treat these acute diseases and make the drug quickly reach a certain release concentration in the body to achieve a therapeutic effect, it is mostly in the form of injections. However, injections have high side effects and are difficult for patients to use directly in daily life. Therefore, dexamethasone acetate tablets are more common for relieving some daily symptoms. However, the disintegration and dissolution efficiency of existing tablets are low. After oral administration, the drug cannot be dissolved to a certain concentration in a short period of time, and the effect on relieving acute symptoms is poor. Therefore, adjusting the auxiliary material components of the tablets to improve the dissolution efficiency of dexamethasone acetate is an important research direction at this stage. Summary of the invention

[0004] In view of the shortcomings of the prior art, the present invention provides a dexamethasone acetate tablet and a preparation method thereof, which can quickly disintegrate and dissolve a large amount of dexamethasone acetate in a short time, and also ensure the long-term dissolution of subsequent drugs, thereby achieving early rapid disintegration of the tablet and subsequent sustained release.

[0005] To achieve the above objectives, the technical solution of the present invention is implemented through the following technical solutions:

[0006] The invention discloses a dexamethasone acetate tablet. The dexamethasone acetate tablet comprises the following raw materials in parts by weight: 2-8 parts of dexamethasone acetate, 400-450 parts of corn starch, 30-50 parts of sucrose fatty acid ester, 50-80 parts of modified microcrystalline cellulose, 180-200 parts of sucrose, 20-40 parts of sorbitol, 6-10 parts of sodium carboxymethyl starch, 5-8 parts of magnesium stearate and 0.5-0.9 parts of sodium lauryl sulfate. The modified microcrystalline cellulose is obtained by mixing microcrystalline cellulose and pregelatinized starch with water, fully shearing and stirring, and then subjecting to high-pressure treatment.

[0007] Preferably, the method for preparing the modified microcrystalline cellulose comprises the following steps:

[0008] S1, adding water to corn starch and heating it to 65-70°C for semi-gelatinization, and then drying to obtain semi-gelatinized starch for later use;

[0009] S2, mixing microcrystalline cellulose and semi-gelatinized starch in a mass ratio of 4-6:1, and then adding water to adjust the water content to 60%-80%, to obtain a mixture for use;

[0010] S3, stirring the above mixture at a speed of 100-120r / min for 20-30min, and then drying and crushing to obtain a crushed material for standby use;

[0011] S4. Add 8-10 times the volume of deionized water to the above-mentioned crushed material, increase the pressure to 6-8 MPa, stir and homogenize, and then freeze-dry to obtain modified microcrystalline cellulose.

[0012] Preferably, the time for the semi-gelatinization treatment in step S1 is 20-30 minutes.

[0013] Preferably, the temperature of drying and crushing in step S3 is 40-60° C., and the crushed product is sieved through a 20-mesh sieve.

[0014] Preferably, the stirring and homogenizing speed in step S4 is 400-600 r / min, and the homogenizing time is 30-40 min.

[0015] The preparation method of dexamethasone acetate tablets comprises the following steps:

[0016] (1) corn starch and sucrose fatty acid ester are mixed and added to deionized water to be fully stirred and dissolved, and then dexamethasone acetate is added and stirred evenly, and then the water is evaporated to control the water content to 60%-80%, and a mixed slurry is obtained for standby use;

[0017] (2) adding modified microcrystalline cellulose to the mixed slurry, kneading and stirring to be uniform, and then drying to obtain a mixed material for later use;

[0018] (3) mixing sucrose and the mixture prepared in the above step (1) and then crushing them, adding sorbitol, sodium carboxymethyl starch, magnesium stearate and sodium lauryl sulfate, mixing and tableting to obtain dexamethasone acetate tablets.

[0019] Preferably, in step (1), the corn starch and sucrose fatty acid ester are mixed and added to deionized water and stirred and dissolved at a temperature of 55-60° C., a stirring speed of 80-120 r / min, a stirring and dissolving time of 8-10 min, and the stirring time after adding dexamethasone acetate is 10-15 min.

[0020] Preferably, the kneading and stirring speed in step (2) is 40-60 r / min, and the stirring time is 20-30 min.

[0021] Preferably, in the step (3), the sucrose is mixed with the mixed material and then crushed to pass through an 18-mesh sieve, and the tableting pressure is 5-10 KN.

[0022] The present invention provides a dexamethasone acetate tablet and a preparation method thereof, which have the advantages over the prior art in that:

[0023] The invention adopts modified microcrystalline cellulose, sucrose fatty acid ester and corn starch as main auxiliary materials, wherein the modified microcrystalline cellulose is prepared by mixing microcrystalline cellulose with semi-gelatinized starch and then subjected to high pressure modification, so as to effectively adsorb drugs and enhance the hydrophilic effect of the auxiliary materials; and the mixed with other auxiliary materials can quickly absorb water and realize disintegration at an early stage, that is, quickly release a large amount of dexamethasone acetate components, and subsequently the auxiliary materials absorb water and swell to generate viscosity, so that the drugs are wrapped and the release of the drugs is slowed down, so that the purpose of quickly releasing a certain concentration of the dexamethasone acetate drug at an early stage and slowly releasing it at a later stage can be achieved, thereby comprehensively improving the timeliness and long-term effect of the treatment. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention is clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] Embodiment 1:

[0026] Preparation of raw materials:

[0027] 1. Prepare the raw materials according to Table 1 below:

[0028] Table 1

[0029]

[0030]

[0031] 2. Preparation of modified microcrystalline cellulose:

[0032] (1) adding water to corn starch and heating it to 70°C for semi-gelatinization for 25 minutes, and then drying at 50°C to obtain semi-gelatinized starch;

[0033] (2) mixing microcrystalline cellulose and semi-gelatinized starch in a mass ratio of 5:1, and then adding water to adjust the water content to 70% to obtain a mixture;

[0034] (3) The mixture was stirred at a speed of 120 r / min for 25 min, dried at 55° C., and then crushed through a 20-mesh sieve to obtain a crushed material;

[0035] (4) Add 8 times the volume of deionized water to the crushed material, increase the pressure to 7 MPa, stir and homogenize at a speed of 500 r / min for 35 min, and then freeze-dry to obtain modified microcrystalline cellulose.

[0036] Embodiment 2:

[0037] Preparation of dexamethasone acetate tablets (production specification of 66,700 tablets):

[0038] (1) Select the raw materials in the above embodiment 1 for preparation:

[0039] 0.05kg dexamethasone acetate, 4.55kg corn starch, 0.4kg sucrose fatty acid ester, 0.57kg modified microcrystalline cellulose, 2kg sucrose, 0.4kg sorbitol, 0.08kg sodium carboxymethyl starch, 0.06kg magnesium stearate, and 0.007kg sodium lauryl sulfate.

[0040] (2) corn starch and sucrose fatty acid ester were mixed and added into deionized water with a total volume of 10 times, and the mixture was stirred and dissolved at a speed of 100 r / min at a water bath temperature of 55° C. for 10 min, and then dexamethasone acetate was added, and the mixture was stirred at a speed of 100 r / min for 12 min, and then the water was evaporated to control the water content at 70%, thereby obtaining a mixed slurry;

[0041] (3) adding modified microcrystalline cellulose to the above mixed slurry, kneading and stirring at a speed of 50 r / min for 25 min, and then drying at 55° C. to obtain a mixed material;

[0042] (4) After mixing sucrose and the mixed material, the mixture was crushed and passed through an 18-mesh sieve, and then sorbitol, sodium carboxymethyl starch, magnesium stearate, and sodium lauryl sulfate were added and mixed using an EYH-6000A two-dimensional motion mixer. The mixture was then tableted using a ZP35A rotary tablet press, with the pressure controlled at 8 kN and the rotation speed ≤ 28 r / min to obtain dexamethasone acetate tablets.

[0043] Comparative Example 1:

[0044] Preparation of dexamethasone acetate tablets (with a production specification of 66,700 tablets, the difference compared to Example 2 is that microcrystalline cellulose is used instead of modified microcrystalline cellulose):

[0045] (1) Select the raw materials in the above embodiment 1 for preparation:

[0046] 0.05kg dexamethasone acetate, 4.55kg corn starch, 0.4kg sucrose fatty acid ester, 0.57kg microcrystalline cellulose, 2kg sucrose, 0.4kg sorbitol, 0.08kg sodium carboxymethyl starch, 0.06kg magnesium stearate, and 0.007kg sodium lauryl sulfate.

[0047] (2) corn starch and sucrose fatty acid ester were mixed and added into deionized water with a total volume of 10 times, and the mixture was stirred and dissolved at a speed of 100 r / min at a water bath temperature of 55° C. for 10 min, and then dexamethasone acetate was added, and the mixture was stirred at a speed of 100 r / min for 12 min, and then the water was evaporated to control the water content at 70%, thereby obtaining a mixed slurry;

[0048] (3) adding microcrystalline cellulose to the mixed slurry, kneading and stirring at a speed of 50 r / min for 25 min, and then drying at 55° C. to obtain a mixed material;

[0049] (4) After mixing sucrose and the mixed material, the mixture was crushed and passed through an 18-mesh sieve, and then sorbitol, sodium carboxymethyl starch, magnesium stearate, and sodium lauryl sulfate were added and mixed using an EYH-6000A two-dimensional motion mixer. The mixture was then tableted using a ZP35A rotary tablet press, with the pressure controlled at 8 kN and the rotation speed ≤ 28 r / min to obtain dexamethasone acetate tablets.

[0050] Comparative Example 2:

[0051] Preparation of dexamethasone acetate tablets (with a production specification of 66,700 tablets, the difference compared to Example 2 is that corn starch is used instead of sucrose fatty acid ester):

[0052] (1) Select the raw materials in the above embodiment 1 for preparation:

[0053] 0.05kg dexamethasone acetate, 4.95kg corn starch, 0.57kg modified microcrystalline cellulose, 2kg sucrose, 0.4kg sorbitol, 0.08kg sodium carboxymethyl starch, 0.06kg magnesium stearate, and 0.007kg sodium lauryl sulfate.

[0054] (2) adding corn starch to deionized water 10 times the total volume, stirring and dissolving the mixture at 55° C. in a water bath at 100 r / min for 10 min, then adding dexamethasone acetate, stirring the mixture at 100 r / min for 12 min, evaporating the water, and controlling the water content at 70% to obtain a mixed slurry;

[0055] (3) adding modified microcrystalline cellulose to the above mixed slurry, kneading and stirring at a speed of 50 r / min for 25 min, and then drying at 55° C. to obtain a mixed material;

[0056] (4) After mixing sucrose and the mixed material, the mixture was crushed and passed through an 18-mesh sieve, and then sorbitol, sodium carboxymethyl starch, magnesium stearate, and sodium lauryl sulfate were added and mixed using an EYH-6000A two-dimensional motion mixer. The mixture was then tableted using a ZP35A rotary tablet press, with the pressure controlled at 8 kN and the rotation speed ≤ 28 r / min to obtain dexamethasone acetate tablets.

[0057] Comparative Example 3:

[0058] Preparation of dexamethasone acetate tablets (with a production specification of 66,700 tablets, the difference compared to Example 2 is that corn starch is used instead of sucrose fatty acid ester, and sucrose is used instead of sorbitol):

[0059] (1) Select the raw materials in the above embodiment 1 for preparation:

[0060] 0.05kg dexamethasone acetate, 4.95kg corn starch, 0.57kg modified microcrystalline cellulose, 2.4kg sucrose, 0.08kg sodium starch glycolate, 0.06kg magnesium stearate, and 0.007kg sodium lauryl sulfate.

[0061] (2) adding corn starch to deionized water 10 times the total volume, stirring and dissolving the mixture at 55° C. in a water bath at 100 r / min for 10 min, then adding dexamethasone acetate, stirring the mixture at 100 r / min for 12 min, evaporating the water, and controlling the water content at 70% to obtain a mixed slurry;

[0062] (3) adding modified microcrystalline cellulose to the above mixed slurry, kneading and stirring at a speed of 50 r / min for 25 min, and then drying at 55° C. to obtain a mixed material;

[0063] (4) After mixing sucrose and the mixed material, the mixture is crushed and passed through an 18-mesh sieve, and then sodium carboxymethyl starch, magnesium stearate, and sodium lauryl sulfate are added and mixed using an EYH-6000A two-dimensional motion mixer. The mixture is then tableted using a ZP35A rotary tablet press, with the pressure controlled at 8 kN and the rotation speed ≤ 28 r / min to obtain dexamethasone acetate tablets.

[0064] Comparative Example 4:

[0065] Preparation of dexamethasone acetate tablets (with a production specification of 66,700 tablets, the difference compared with Example 2 is that corn starch is used instead of sucrose fatty acid ester, sucrose is used instead of sorbitol, and microcrystalline cellulose is used instead of modified microcrystalline cellulose):

[0066] (1) Select the raw materials in the above embodiment 1 for preparation:

[0067] 0.05kg dexamethasone acetate, 4.95kg corn starch, 0.57kg microcrystalline cellulose, 2.4kg sucrose, 0.08kg sodium starch glycolate, 0.06kg magnesium stearate, and 0.007kg sodium lauryl sulfate.

[0068] (2) adding corn starch to deionized water 10 times the total volume, stirring and dissolving the mixture at 55° C. in a water bath at 100 r / min for 10 min, then adding dexamethasone acetate, stirring the mixture at 100 r / min for 12 min, evaporating the water, and controlling the water content at 70% to obtain a mixed slurry;

[0069] (3) adding modified microcrystalline cellulose to the above mixed slurry, kneading and stirring at a speed of 50 r / min for 25 min, and then drying at 55° C. to obtain a mixed material;

[0070] (4) After mixing sucrose and the mixed material, the mixture is crushed and passed through an 18-mesh sieve, and then sodium carboxymethyl starch, magnesium stearate, and sodium lauryl sulfate are added and mixed using an EYH-6000A two-dimensional motion mixer. The mixture is then tableted using a ZP35A rotary tablet press, with the pressure controlled at 8 kN and the rotation speed ≤ 28 r / min to obtain dexamethasone acetate tablets.

[0071] Detection:

[0072] 1. The friability (calculated by sampling 1000 tablets) of the dexamethasone acetate tablets prepared in Example 2 and Comparative Examples 1-4 was tested according to the testing method of the 2010 edition of the Chinese Pharmacopoeia. The results are shown in Table 2 below:

[0073] Table 2

[0074] Group friability Example 2 ≤0.8％ Comparative Example 1 ≤0.8％ Comparative Example 2 ≤0.8％ Comparative Example 3 ≤0.8％ Comparative Example 4 ≤0.8％

[0075] 2. The dissolution properties of the dexamethasone acetate tablets prepared in Example 2 and Comparative Examples 1-4 in different solvents were tested:

[0076] 2.1. Detection of dissolution in water:

[0077] Using 1000 mL of pure water solution as solvent, each group of single dexamethasone acetate tablets were placed in pure water, and samples were taken at 1 min, 3 min, 5 min, 15 min, and 30 min to detect the dissolution of prednisone acetate. The specific results are shown in Table 3 below:

[0078] Table 3

[0079]

[0080] 2.2. Detection of dissolution in artificial gastric juice:

[0081] Take 1 mol / mL of dilute hydrochloric acid, then dilute with water, adjust the pH to 1.5, and add 1 g of pepsin per 100 mL, mix well, and prepare artificial gastric juice;

[0082] A single dexamethasone acetate tablet of each group was placed in 1000 mL of artificial gastric juice and allowed to dissolve at a constant temperature of 36°C. Samples were taken at 1 min, 3 min, 5 min, 15 min and 30 min to test the dissolution of dexamethasone acetate of each group. The details are shown in Table 4 below:

[0083] Table 4

[0084]

[0085] From the above test, it can be seen that the dexamethasone acetate tablets prepared in Example 2 have a solubility of more than 50% in aqueous solution in 5 minutes, a solubility of more than 35% in artificial gastric juice in 1 minute, and a solubility of more than 55% in 3 minutes, and can be continuously dissolved for more than 30 minutes, that is, the dexamethasone acetate tablets prepared in Example 2 have the characteristics of early efficient dissolution and subsequent sustained-release dissolution, achieving the purpose of providing a higher concentration of the drug for rapid treatment in the early stage after taking the drug, and subsequent continuous dissolution to ensure the efficacy of the drug.

[0086] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A dexamethasone acetate tablet, characterized in that: The dexamethasone acetate tablets are composed of the following raw materials in parts by weight: 2-8 parts of dexamethasone acetate, 400-450 parts of corn starch, 30-50 parts of sucrose fatty acid ester, 50-80 parts of modified microcrystalline cellulose, 180-200 parts of sucrose, 20-40 parts of sorbitol, 6-10 parts of sodium carboxymethyl starch, 5-8 parts of magnesium stearate, and 0.5-0.9 parts of sodium lauryl sulfate, and the modified microcrystalline cellulose is obtained by mixing microcrystalline cellulose and pregelatinized starch with water, fully shearing and stirring, and then high-pressure treatment.

2. A dexamethasone acetate tablet according to claim 1, characterized in that: The preparation method of the modified microcrystalline cellulose comprises the following steps: S1, adding water to corn starch and heating it to 65-70°C for semi-gelatinization, and then drying to obtain semi-gelatinized starch for later use; S2, mixing microcrystalline cellulose and semi-gelatinized starch in a mass ratio of 4-6:1, and then adding water to adjust the water content to 60%-80%, to obtain a mixture for use; S3, stirring the above mixture at a speed of 100-120r / min for 20-30min, and then drying and crushing to obtain a crushed material for standby use; S4. Add 8-10 times the volume of deionized water to the above-mentioned crushed material, increase the pressure to 6-8 MPa, stir and homogenize, and then freeze-dry to obtain modified microcrystalline cellulose.

3. A dexamethasone acetate tablet according to claim 2, characterized in that: The time of semi-gelatinization treatment in step S1 is 20-30 minutes.

4. A dexamethasone acetate tablet according to claim 2, characterized in that: The temperature of drying and crushing in step S3 is 40-60° C. and the powder is sieved through a 20-mesh sieve.

5. A dexamethasone acetate tablet according to claim 2, characterized in that: The stirring and homogenizing speed in step S4 is 400-600 r / min, and the homogenizing time is 30-40 min.

6. A method for preparing the dexamethasone acetate tablets according to any one of claims 1 to 5, characterized in that: The preparation method comprises the following steps: (1) corn starch and sucrose fatty acid ester are mixed and added to deionized water to be fully stirred and dissolved, and then dexamethasone acetate is added and stirred evenly, and then the water is evaporated to control the water content to 60%-80%, and a mixed slurry is obtained for standby use; (2) adding modified microcrystalline cellulose to the mixed slurry, kneading and stirring to be uniform, and then drying to obtain a mixed material for later use; (3) mixing sucrose and the mixture prepared in the above step (1) and then crushing them, adding sorbitol, sodium carboxymethyl starch, magnesium stearate and sodium lauryl sulfate, mixing and tableting to obtain dexamethasone acetate tablets.

7. The preparation method according to claim 6, characterized in that: In the step (1), the corn starch and sucrose fatty acid ester are mixed and added to deionized water and stirred and dissolved at a temperature of 55-60° C., a stirring speed of 80-120 r / min, a stirring and dissolving time of 8-10 min, and the stirring time after adding dexamethasone acetate is continued for 10-15 min.

8. The preparation method according to claim 6, characterized in that: The kneading and stirring speed in the step (2) is 40-60 r / min, and the stirring time is 20-30 min.

9. The preparation method according to claim 6, characterized in that: In the step (3), the sucrose is mixed with the mixed material and then crushed to pass through an 18-mesh sieve, and the tableting pressure is 5-10 KN.

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