Erythromycin enteric-coated tablet and preparation method thereof

Abstract

The invention provides an erythromycin enteric-coated tablet and a preparation method thereof, and relates to the technical field of erythromycin medicine preparation. The erythromycin enteric-coated tablet is prepared from erythromycin, corn starch, modified corn starch, carboxymethyl starch sodium, sodium dodecyl sulfate, magnesium stearate, cane sugar, ethanol, polyacrylic resin II, polyacrylic resin III and edible triethyl citrate. The defects in the prior art are overcome, the stability of the erythromycin enteric-coated tablet in gastric acid and the disintegration efficiency of the erythromycin enteric-coated tablet in intestinal juice are effectively improved, and the quality and the curative effect of the medicine are comprehensively improved.

Description

Technical Field

[0001] The invention relates to the technical field of erythromycin drug preparation, and in particular to erythromycin enteric-coated tablets and a preparation method thereof. Background Art

[0002] Erythromycin is a macrolide antibiotic used as an alternative to penicillin-allergic patients in the treatment of the following infections: acute tonsillitis, acute pharyngitis, and sinusitis caused by hemolytic streptococci, Streptococcus pneumoniae, etc.; scarlet fever and cellulitis caused by hemolytic streptococci; diphtheria and diphtheria carriers; gas gangrene, anthrax, and tetanus; actinomycosis; syphilis; listeriosis; Legionnaires' disease; Mycoplasma pneumonia; Chlamydia pneumoniae pneumonia; urogenital infections caused by Chlamydia and Mycoplasma; Chlamydia trachomatis conjunctivitis; Neisseria gonorrhoeae infections; oral infections caused by anaerobic bacteria; Campylobacter jejuni enteritis; whooping cough, etc.

[0003] Due to certain defects in the structural characteristics of erythromycin, its C-6 and C-12 hydroxyl groups and C-9 carbonyl group can form acetal structures under acid catalysis, which are unstable under acidic conditions and easily decompose and lose activity below pH 6. Therefore, it is easily destroyed by gastric acid and loses its effect when taken orally, resulting in poor bioavailability and difficulty in controlling the dosage. Therefore, it is usually prepared into enteric-coated preparations.

[0004] However, existing erythromycin enteric-coated tablets may release a certain amount of drug under gastric acid conditions. If the tablets remain in the stomach for a long time, the drug efficacy will be reduced. In addition, the drug release stability in intestinal fluid is also poor, which seriously affects the quality and efficacy of the product. Summary of the invention

[0005] In view of the deficiencies in the prior art, the present invention provides an erythromycin enteric-coated tablet and a preparation method thereof, which effectively improves the stability of the erythromycin enteric-coated tablet in gastric acid and the disintegration efficiency in intestinal fluid, and comprehensively improves the quality and efficacy of the drug.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0007] The invention discloses an erythromycin enteric-coated tablet. The erythromycin enteric-coated tablet is prepared from the following raw materials in parts by weight: 300 parts of erythromycin, 80-100 parts of corn starch, 40-50 parts of modified corn starch, 40-60 parts of sodium carboxymethyl starch, 1.5-2 parts of sodium dodecyl sulfate, 6-9 parts of magnesium stearate, 5-8 parts of sucrose, 350-450 parts of ethanol, 12-15 parts of polyacrylic acid resin II, 5-8 parts of polyacrylic acid resin III and 1-1.8 parts of edible triethyl citrate. The modified corn starch is prepared by boiling corn starch with water, cooling it and freeze-drying it, repeating the operation for 3 times and then subjecting it to microwave shaping.

[0008] Preferably, the preparation method of the modified corn starch comprises the following steps:

[0009] S1-1, add 3-5 times volume of corn starch to deionized water, heat, stir and boil for 15-20 minutes, then naturally cool to room temperature to form a gel-like material, freeze-dry and grind to obtain a preliminary material;

[0010] S1-2. Repeat the above operation for 3 times for the preliminary material. After the final freeze-drying and pulverization, place the preliminary material in a microwave oven and microwave it at 100-120° C. for 20-30 seconds to obtain modified corn starch.

[0011] The preparation method of erythromycin enteric-coated tablets comprises the following steps:

[0012] (1) erythromycin, 4 / 5-2 / 3 of the total amount of corn starch, 1 / 2-1 / 3 of the total amount of modified corn starch, and 1 / 5-2 / 5 of the total amount of sodium carboxymethyl starch are stirred and mixed to obtain a mixture for use;

[0013] (2) mixing sodium dodecyl sulfate, remaining corn starch, modified corn starch and sugar cane, adding the mixture into boiling purified water, stirring the mixture evenly, and obtaining starch syrup for later use;

[0014] (3) Mixing 3 / 4-2 / 3 of the total amount of starch syrup with the above mixture, stirring, sieve granulation, and drying, and then mixing with the remaining starch syrup, and then continuing to dry to obtain prefabricated granules for use;

[0015] (4) The prefabricated granules are sized using a sieve, and then mixed with magnesium stearate and the remaining sodium starch glycolate, and placed in a mixer to prepare mixed granules, which are then tableted to obtain tablet cores for later use;

[0016] (5) Add polyacrylic acid resin II, polyacrylic acid resin III, and edible triethyl citrate into ethanol, stir thoroughly to prepare a coating solution for later use;

[0017] (6) Add the tablet cores into a coating machine and spray-coat with a coating liquid to obtain erythromycin enteric-coated tablets.

[0018] Preferably, the mixing method in step (1) is to stir and mix in a mixer for 10-15 minutes.

[0019] Preferably, the stirring time in step (2) is 3-5 min, and the mixture is cooled at room temperature after stirring.

[0020] Preferably, the sieve granulation in step (3) is granulation using a 16-mesh nylon sieve.

[0021] Preferably, the drying method in step (3) is to place the mixture in a constant temperature oven and dry it at 75±5°C.

[0022] Preferably, in step (4), a 14-mesh stainless steel screen is used for granulation, and the tableting pressure is 5-15N.

[0023] Preferably, the parameters set for the coating machine in step (6) are 4-6 rpm, an air inlet temperature of 45°C, and an air outlet temperature of 40°C.

[0024] The present invention provides an erythromycin enteric-coated tablet and a preparation method thereof, which has the advantages of:

[0025] The erythromycin enteric-coated tablets prepared by the invention can remain stable in gastric acid for a long time, reduce the dissolution of the drug, and can quickly disintegrate in intestinal fluid to release the drug. In addition, the preparation process is carried out by mixing corn starch and modified corn starch and providing an outer layer of syrup, thereby reducing the influence of the outermost coating material on the drug, ensuring the storage performance of the drug, and comprehensively improving the use effect of the drug. DETAILED DESCRIPTION

[0026] 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.

[0027] The raw materials used in the following examples are shown in Table 1:

[0028] Table 1

[0029]

[0030]

[0031] Embodiment 1:

[0032] Preparation of modified corn starch:

[0033] 1. Modified corn starch A:

[0034] (1) Add 4 times the volume of corn starch to deionized water, heat and stir and boil for 18 minutes, then naturally cool to room temperature to form a gel-like material, freeze-dry and grind to obtain a preliminary material;

[0035] (2) Add 4 times the volume of deionized water to the primary material, heat and stir and boil for 18 minutes, then naturally cool to room temperature to form a gel-like material, freeze-dry and grind to obtain a secondary material;

[0036] (3) Add 4 times the volume of deionized water to the secondary material, heat and stir and boil for 18 minutes, then naturally cool to room temperature to form a gel-like material, freeze-dry and grind to obtain the tertiary material;

[0037] (4) Add 4 times the volume of deionized water to the tertiary material, heat, stir and boil for 18 minutes, then naturally cool to room temperature to form a gel-like material, freeze-dry and grind to obtain the quaternary material;

[0038] (5) The fourth batch of materials were placed in a microwave oven and subjected to microwave treatment at 120° C. for 20 seconds to obtain modified corn starch A.

[0039] 2. Modified corn starch B:

[0040] (1) Add 4 times the volume of corn starch to deionized water, heat and stir and boil for 18 minutes, then naturally cool to room temperature to form a gel-like material, freeze-dry and grind to obtain a preliminary material;

[0041] (2) The preliminary material was placed in a microwave oven and subjected to microwave treatment at 120° C. for 20 seconds to obtain modified corn starch B.

[0042] 3. Modified corn starch C:

[0043] Corn starch was added into 4 times volume of deionized water, heated, stirred and boiled for 18 minutes, then naturally cooled to room temperature to form a gelatinous material, freeze-dried and crushed to obtain modified corn starch C.

[0044] Embodiment 2:

[0045] Preparation of erythromycin enteric-coated tablets:

[0046] (1) Prepare materials by weight: 30 kg erythromycin, 9 kg corn starch, 4.5 kg modified corn starch, 5 kg sodium carboxymethyl starch, 0.18 kg sodium dodecyl sulfate, 0.8 kg magnesium stearate, 0.65 kg sucrose, 40 kg ethanol, 1.4 kg polyacrylic acid resin II, 6 kg polyacrylic acid resin III, and 0.15 kg edible triethyl citrate;

[0047] (2) adding erythromycin, 6.8 kg corn starch, 2 kg modified corn starch, and 1.5 kg sodium carboxymethyl starch into a mixer and stirring for 10 min to obtain a mixture for later use;

[0048] (3) Mix sodium dodecyl sulfate, remaining corn starch, modified corn starch and sugar cane, add to 15 kg of boiling purified water, stir thoroughly for 4 minutes, and cool at room temperature to obtain starch syrup for later use;

[0049] (4) Pour 3 / 4 of the total amount of starch syrup into the above mixer and stir the mixture for 5 minutes to obtain a soft material. Pour the soft material into a swing granulator and operate according to the "Standard Operating Procedure for YK-160 / YK160A Swing Granulator" (SOP-02EM-022). Use a 16-mesh nylon screen to granulate. Spread the prepared wet granules evenly on a stainless steel plate and send them into a hot air circulation oven. The temperature is controlled at 75±5°C for 7 hours. After drying, turn off the steam, cool to below 40°C, and pull out the material cart to obtain preliminary dried granules. Mix the remaining starch syrup and stir evenly. Then spread them on a stainless steel plate and continue to dry them in a hot air circulation oven at 75±5°C for 2 hours to obtain prefabricated granules.

[0050] (5) Pour the pre-made granules into the bucket of a swing granulator and operate according to the Standard Operating Procedure for YK-160 / YK160A Swing Granulator (SOP-02EM-022). Use a 14-mesh stainless steel screen to granulate. Add the granulated dry granules into a two-dimensional motion mixer. Add magnesium stearate and the remaining sodium carboxymethyl starch into the mixer and operate according to the Standard Operating Procedure for EYH-4000 Two-Dimensional Motion Mixer (SOP-02EM-037). Set the operating frequency of the swing motor and the speed motor to 40 Hz and the mixing time to 60 min to mix the granules. Then, use a ZP35A / B tablet press to set the speed to 25 rpm and the pressure to 10 KN to obtain tablet cores.

[0051] (6) Add polyacrylic acid resin II, polyacrylic acid resin III, and edible triethyl citrate into ethanol, stir and dissolve them thoroughly to prepare a coating solution for use;

[0052] (7) Add the tablet cores into a BG-650 high-efficiency coating machine and operate according to the Standard Operating Procedure for BG-650 High-efficiency Coating Machine (SOP-02EM-099), set the speed to 4-6 rpm, set the inlet air temperature to 45°C, and the outlet air temperature to 40°C, turn on the machine, start the machine, and then open the peristaltic pump and compressed air valve to spray coating to obtain erythromycin enteric-coated tablets.

[0053] And referring to the above preparation method and ingredients, different groups of erythromycin enteric-coated tablets were prepared using different modified corn starches in Example 1, as shown in Table 2 below:

[0054] Table 2

[0055] Group Experimental Group 1 Experimental Group 2 Experimental Group 3 Modified corn starch Modified corn starch A Modified corn starch B Modified corn starch C

[0056] Comparative Example 1:

[0057] Preparation of erythromycin enteric-coated tablets:

[0058] The ingredient formula is the same as that of the above-mentioned experimental group 1, and the preparation processes (1)-(3) and (5)-(7) are the same as those of Example 2; the specific operation of step (4) is as follows:

[0059] (4) Pour the starch syrup into the above mixer and stir the mixture for 5 minutes to obtain a soft material, pour the soft material into the swing granulator, operate according to the "YK-160 / YK160A Swing Granulator Standard Operating Procedure" (SOP-02EM-022), use a 16-mesh nylon screen to granulate, spread the prepared wet granules evenly on a stainless steel plate, send them into a hot air circulation oven, control the temperature at 75±5°C, and dry them for 7 hours. After drying, turn off the steam, cool it to below 40°C, and pull out the material cart to obtain prefabricated granules;

[0060] Detection:

[0061] The dissolution of erythromycin enteric-coated tablets (0.125 g / tablet) prepared in experimental groups 1-3 and comparative example 1 in the above embodiment 2 was detected:

[0062] 1. Detection of dissolution in artificial gastric juice:

[0063] 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;

[0064] Each group of single erythromycin enteric-coated tablets was placed in 1000 mL of artificial gastric juice, and samples were taken at 36°C after standing for 10 min, 30 min, and 60 min to detect the dissolution of erythromycin in each group. The details are shown in Table 3 below:

[0065] Table 3

[0066]

[0067] Each group of erythromycin enteric-coated tablets was placed in an environment with a humidity of 60% and a temperature of 25±2°C for 1 month, 3 months, and 6 months, and then placed in artificial gastric juice for 60 minutes in the above manner to detect the dissolution of erythromycin in each group. The specific results are shown in Table 4 below:

[0068] Table 4

[0069]

[0070] 2. Detection of dissolution in artificial intestinal fluid:

[0071] Take 6.8g of potassium dihydrogen phosphate, add 500ml of water to dissolve it, and adjust the pH value to 6.8 with 0.4% sodium hydroxide solution; take 10g of pancreatic enzyme, add appropriate amount of water to dissolve it, mix the two liquids, and dilute with water to 1000ml to prepare artificial intestinal fluid for use;

[0072] Each group of single erythromycin enteric-coated tablets was placed in 1000 mL of artificial gastric juice, and samples were taken at 36°C after standing for 1 min, 5 min, and 15 min to detect the dissolution of erythromycin in each group. The details are shown in Table 5 below:

[0073] Table 5

[0074]

[0075] Each group of erythromycin enteric-coated tablets was placed in an environment with a humidity of 60% and a temperature of 25±2°C for 1 month, 3 months, and 6 months, and then placed in artificial intestinal fluid for 15 minutes in the above manner to detect the dissolution of erythromycin in each group. The specific results are shown in Table 6 below:

[0076] Table 6

[0077]

[0078] From the above tests, it can be seen that the erythromycin enteric-coated tablets prepared in experimental group 1 can maintain high stability in artificial gastric juice, achieve rapid dissolution and disintegration in artificial intestinal juice, and the erythromycin enteric-coated tablets prepared in experimental group 1 have high storage stability.

[0079] 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. An erythromycin enteric-coated tablet, characterized in that: The erythromycin enteric-coated tablets are prepared from the following raw materials in parts by mass: 300 parts of erythromycin, 80-100 parts of corn starch, 40-50 parts of modified corn starch, 40-60 parts of sodium carboxymethyl starch, 1.5-2 parts of sodium dodecyl sulfate, 6-9 parts of magnesium stearate, 5-8 parts of sucrose, 350-450 parts of ethanol, 12-15 parts of polyacrylic acid resin II, 5-8 parts of polyacrylic acid resin III, and 1-1.8 parts of edible triethyl citrate, wherein the modified corn starch is prepared by boiling corn starch with water, cooling it, freeze-drying it, repeating the operation for 3 times, and then subjecting it to microwave shaping.

2. Erythromycin enteric-coated tablets according to claim 1, characterized in that The preparation method of the modified corn starch comprises the following steps: S1-1, add 3-5 times volume of corn starch to deionized water, heat, stir and boil for 15-20 minutes, then naturally cool to room temperature to form a gel-like material, freeze-dry and grind to obtain a preliminary material; S1-2. Repeat the above operation for 3 times for the preliminary material. After the final freeze-drying and pulverization, place the preliminary material in a microwave oven and microwave it at 100-120° C. for 20-30 seconds to obtain modified corn starch.

3. A method for preparing erythromycin enteric-coated tablets according to any one of claims 1 to 2, characterized in that: The preparation method comprises the following steps: (1) erythromycin, 4 / 5-2 / 3 of the total amount of corn starch, 1 / 2-1 / 3 of the total amount of modified corn starch, and 1 / 5-2 / 5 of the total amount of sodium carboxymethyl starch are stirred and mixed to obtain a mixture for use; (2) mixing sodium dodecyl sulfate, remaining corn starch, modified corn starch and sugar cane, adding the mixture into boiling purified water, stirring the mixture evenly, and obtaining starch syrup for later use; (3) Mixing 3 / 4-2 / 3 of the total amount of starch syrup with the above mixture, stirring, sieve granulation, and drying, and then mixing with the remaining starch syrup, and then continuing to dry to obtain prefabricated granules for use; (4) The prefabricated granules are sized using a sieve, and then mixed with magnesium stearate and the remaining sodium starch glycolate, and placed in a mixer to prepare mixed granules, which are then tableted to obtain tablet cores for later use; (5) Add polyacrylic acid resin II, polyacrylic acid resin III, and edible triethyl citrate into ethanol, stir thoroughly to prepare a coating solution for later use; (6) Add the tablet cores into a coating machine and spray-coat with a coating liquid to obtain erythromycin enteric-coated tablets.

4. The preparation method according to claim 3, characterized in that: The mixing method in step (1) is to stir and mix in a mixer for 10-15 minutes.

5. The preparation method according to claim 3, characterized in that: The stirring time in step (2) is 3-5 min, and the mixture is cooled at room temperature after stirring.

6. The preparation method according to claim 3, characterized in that: The sieve granulation in step (3) is granulation using a 16-mesh nylon sieve.

7. The preparation method according to claim 3, characterized in that: The drying method in step (3) is to place the mixture in a constant temperature oven and dry it at 75±5°C.

8. The preparation method according to claim 3, characterized in that: In the step (4), a 14-mesh stainless steel screen is used for granulation, and the tableting pressure is 5-15N.

9. The preparation method according to claim 3, characterized in that: The parameters set for the coating machine in step (6) are 4-6 revolutions per minute, an air inlet temperature of 45°C, and an air outlet temperature of 40°C.

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