Erythromycin enteric-coated tablet and preparation method thereof

Abstract

The invention discloses an erythromycin enteric-coated tablet and a preparation method thereof. The enteric-coated tablet comprises a tablet core, a middle layer, an isolating layer and an enteric-coated layer, wherein the tablet core is prepared from the following components in parts by mass: 60 to 65 parts of erythromycin, 5 to 10 parts of microcrystalline cellulose, 2 to 5 parts of povidone, 15 to 30 parts of water, 0.5 to 5 parts of sodium citrate, 1 to 3 parts of cross-linked povidone and 1 to 3 parts of hydroxy propyl cellulose; the middle layer is prepared from 1 to 5 parts of cross-linked sodium methyl cellulose, 0.3 to 0.5 part of silicon dioxide and 0.2 to 0.5 part of magnesium stearate; the isolating layer comprises 8-10 parts of a gastric-soluble coating premix; and the enteric layer comprises 25-40 parts of an enteric coating premix. By optimizing the proportion of the coating material and improving the coating process, the prepared erythromycin enteric-coated tablet has a stable drug release characteristic and can keep good stability in the storage process.

Description

Technical Field

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

[0002] Erythromycin has antibacterial activity against Staphylococcus (except methicillin-resistant strains), various groups of streptococci and Gram-positive rods. Neisseria, Haemophilus influenzae, Bordetella pertussis, etc. are also sensitive to this product. This product also has antibacterial effects on various anaerobic bacteria except Bacteroides fragilis and Fusobacterium. It also has inhibitory effects on Legionella, Campylobacter fetus, some spirochetes, Mycoplasma pneumoniae, Rickettsia and Chlamydia.

[0003] Erythromycin base and its salts are readily absorbed in the active microbial form when taken orally. Erythromycin binds to plasma proteins after absorption and diffuses readily into most body fluids. In the absence of meningitis, erythromycin concentrations in the cerebrospinal fluid are low, but in the presence of meningitis, erythromycin can cross the blood-brain barrier. Erythromycin can cross the placental barrier, but plasma concentrations in the fetus are low. Erythromycin can be excreted in human milk. Erythromycin is not eliminated by peritoneal dialysis or hemodialysis. In the presence of normal liver function, erythromycin is concentrated primarily in the liver and excreted via bile; after oral administration, less than 5% of the administered dose is present in the urine. The LD50 of erythromycin in mice is 2927 mg / kg when administered orally and 1849 mg / kg when administered subcutaneously. In studies with rats, mice, and rabbits, no evidence of carcinogenicity, mutagenicity, impaired fertility, teratogenicity, or embryotoxicity was found for erythromycin. However, as an antibiotic, erythromycin is unstable under acidic conditions and rapidly decomposes and loses activity when the pH is below 6. Therefore, when administered orally, erythromycin is easily destroyed by gastric acid, resulting in reduced bioavailability and difficulty in achieving an effective therapeutic dose. In order to solve this problem, erythromycin is usually made into an enteric-coated preparation. The characteristic of this type of preparation is that it will not dissolve in the highly acidic stomach environment, but will enter the small intestine through the stomach, and will only begin to dissolve and release the drug when it reaches the alkaline environment of the small intestine. This can protect erythromycin from being destroyed by gastric acid, ensure that it reaches a sufficient concentration in the small intestine, and thus improve the bioavailability of the drug.

[0004] The existing erythromycin enteric-coated tablets have the problem of unstable release, and the release will gradually decrease during storage, which seriously affects the quality and efficacy of the product. In view of this, it is necessary to propose an erythromycin enteric-coated tablet with a reasonable composition ratio and stable drug release. Summary of the invention

[0005] In view of the shortcomings of the prior art, the primary purpose of the present invention is to provide an erythromycin enteric-coated tablet, which comprises a tablet core, an intermediate layer, an isolation layer and an enteric layer. The present invention optimizes the ratio of coating materials and improves the coating process, so that the prepared erythromycin enteric-coated tablet has stable drug release characteristics and can maintain good stability during storage.

[0006] Another object of the present invention is to provide a method for preparing the erythromycin enteric-coated tablets, which is simple and easy to implement and suitable for large-scale industrial production.

[0007] The purpose of the present invention is achieved through the following technical solutions: An erythromycin enteric-coated tablet, comprising a tablet core, an intermediate layer, an isolation layer and an enteric-coated layer; wherein, by weight, the tablet core comprises 60-65 parts of erythromycin, 5-10 parts of microcrystalline cellulose, 2-5 parts of povidone, 15-30 parts of water, 0.5-5 parts of sodium citrate, 1-3 parts of cross-linked povidone and 1-3 parts of hydroxypropyl cellulose; The middle layer includes 1 to 5 parts of cross-linked sodium methylcellulose, 0.3 to 0.5 parts of silicon dioxide and 0.2 to 0.5 parts of magnesium stearate; The isolation layer includes 8 to 10 parts of gastric soluble coating premix; The enteric layer includes 25 to 40 parts of an enteric coating premix.

[0008] Preferably, the tablet core comprises, by weight, 62 to 65 parts of erythromycin, 8 to 10 parts of microcrystalline cellulose, 3 to 5 parts of povidone, 15 to 20 parts of water, 3 to 5 parts of sodium citrate, 2 to 3 parts of cross-linked povidone and 1 to 3 parts of hydroxypropyl cellulose.

[0009] Preferably, the middle layer comprises 3 to 5 parts of cross-linked sodium methylcellulose, 0.3 to 0.5 parts of silicon dioxide and 0.3 to 0.5 parts of magnesium stearate.

[0010] Preferably, the gastric soluble coating premix comprises hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2 to 3:1.

[0011] Preferably, the enteric coating premix comprises hydroxypropyl methylcellulose phthalate, triethyl citrate and polyethylene glycol in a mass ratio of 5-7:1-2:0.5-1.

[0012] The preparation method of the above-mentioned erythromycin enteric-coated tablets comprises the following steps: (1) According to the proportion of raw material components, erythromycin, microcrystalline cellulose, povidone, water, sodium citrate, crospovidone and hydroxypropyl cellulose are fully mixed and granulated to obtain wet granules; cross-linked methylcellulose sodium, silicon dioxide and magnesium stearate are mixed with the wet granules, and dried, granulated and tableted to obtain tablet cores; (2) Adding water to the gastric-soluble coating premix to prepare a gastric-soluble coating solution, spraying the gastric-soluble coating solution evenly on the surface of the tablet core, and drying after spraying; (3) Add water to the enteric coating premix to prepare an enteric coating solution, and spray the enteric coating solution prepared by adding water onto the surface of the tablets that have been dried in step (2) by spraying, and finally dry again.

[0013] Preferably, in step (2), the drying process is fluidized bed drying or oven drying.

[0014] Preferably, in step (2), the drying temperature is 30-40°C.

[0015] Preferably, in step (3), the second drying is performed by fluidized bed drying or oven drying.

[0016] Preferably, in step (3), the temperature for re-drying is 30-50°C.

[0017] Compared with the prior art, the beneficial effects of the present invention include: The present invention optimizes the ratio of coating materials and improves the coating process, so that the prepared erythromycin enteric-coated tablets not only have stable drug release characteristics, but also can maintain good stability during storage. In addition, the preparation process of the present invention is simple and easy to operate, and is suitable for large-scale industrial production. Through the above-mentioned optimization and improvement, the present invention not only improves the quality and efficacy of erythromycin enteric-coated tablets, but also greatly improves its production efficiency and economy, and has significant application prospects. DETAILED DESCRIPTION

[0018] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0019] Example 1 An erythromycin enteric-coated tablet, comprising a tablet core, an intermediate layer, an isolation layer and an enteric-coated layer; wherein, by weight, the tablet core contains 62 parts of erythromycin, 8 parts of microcrystalline cellulose, 3 parts of povidone, 15 parts of water, 3 parts of sodium citrate, 2 parts of cross-linked povidone and 3 parts of hydroxypropyl cellulose; The middle layer contains 3 parts of cross-linked methylcellulose sodium, 0.3 parts of silicon dioxide and 0.3 parts of magnesium stearate; The isolation layer contains 8 parts of gastric soluble coating premix; the enteric layer contains 25 parts of enteric coating premix. The gastric soluble coating premix is ​​a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2:1; the enteric coating premix is ​​a mixture of hydroxypropyl methylcellulose phthalate, triethyl citrate and polyethylene glycol in a mass ratio of 5:1:0.5.

[0020] The preparation method of erythromycin enteric-coated tablets described in Example 1 comprises the following specific steps: (1) According to the proportion of raw material components, erythromycin, microcrystalline cellulose, povidone, water, sodium citrate, crospovidone and hydroxypropyl cellulose are fully mixed and granulated to obtain wet granules; cross-linked methylcellulose sodium, silicon dioxide and magnesium stearate are mixed with the wet granules, and dried, granulated and tableted to obtain tablet cores; (2) Add water to the gastric soluble coating premix to prepare a gastric soluble coating solution, and spray the gastric soluble coating solution evenly on the surface of the tablet core by spraying. After spraying, perform fluidized bed drying at a drying temperature of 30°C. (3) Add water to the enteric coating premix to prepare an enteric coating solution, and spray the enteric coating solution prepared by adding water onto the surface of the tablets that have been dried in step (2) by spraying, and finally perform fluidized bed drying again at a drying temperature of 30° C. After drying, erythromycin enteric-coated tablets are prepared.

[0021] Example 2 An erythromycin enteric-coated tablet, comprising a tablet core, an intermediate layer, an isolation layer and an enteric-coated layer; wherein, by weight, the tablet core contains 65 parts of erythromycin, 10 parts of microcrystalline cellulose, 5 parts of povidone, 20 parts of water, 5 parts of sodium citrate, 3 parts of cross-linked povidone and 3 parts of hydroxypropyl cellulose; The middle layer contains 5 parts of cross-linked methylcellulose sodium, 0.5 parts of silicon dioxide and 0.5 parts of magnesium stearate; The isolation layer contains 10 parts of gastric soluble coating premix; the enteric layer contains 40 parts of enteric coating premix. The gastric soluble coating premix is ​​a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 3:1; the enteric coating premix is ​​a mixture of hydroxypropyl methylcellulose phthalate, triethyl citrate and polyethylene glycol in a mass ratio of 7:2:1.

[0022] The preparation method of erythromycin enteric-coated tablets described in Example 2 comprises the following specific steps: (1) According to the proportion of raw material components, erythromycin, microcrystalline cellulose, povidone, water, sodium citrate, crospovidone and hydroxypropyl cellulose are fully mixed and granulated to obtain wet granules; cross-linked methylcellulose sodium, silicon dioxide and magnesium stearate are mixed with the wet granules, and dried, granulated and tableted to obtain tablet cores; (2) Add water to the gastric-soluble coating premix to prepare a gastric-soluble coating solution, and spray the gastric-soluble coating solution evenly on the surface of the tablet core by spraying. After spraying, the tablet is dried in an oven at a temperature of 30°C. (3) Add water to the enteric coating premix to prepare an enteric coating solution, and spray the enteric coating solution prepared by adding water onto the surface of the tablets that have been dried in step (2) by spraying, and finally perform fluidized bed drying again at a drying temperature of 35° C. After drying, erythromycin enteric-coated tablets are prepared.

[0023] Example 3 An erythromycin enteric-coated tablet, comprising a tablet core, an intermediate layer, an isolation layer and an enteric-coated layer; wherein, by weight, the tablet core contains 60 parts of erythromycin, 5 parts of microcrystalline cellulose, 3 parts of povidone, 20 parts of water, 4 parts of sodium citrate, 2 parts of cross-linked povidone and 1 part of hydroxypropyl cellulose; The middle layer contains 1 part of cross-linked methylcellulose sodium, 0.3 parts of silicon dioxide and 0.2 parts of magnesium stearate; The isolation layer contains 8 parts of gastric soluble coating premix; the enteric layer contains 40 parts of enteric coating premix. The gastric soluble coating premix is ​​a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 3:1; the enteric coating premix is ​​a mixture of hydroxypropyl methylcellulose phthalate, triethyl citrate and polyethylene glycol in a mass ratio of 7:1:1.

[0024] The preparation method of erythromycin enteric-coated tablets described in Example 3 comprises the following specific steps: (1) According to the proportion of raw material components, erythromycin, microcrystalline cellulose, povidone, water, sodium citrate, crospovidone and hydroxypropyl cellulose are fully mixed and granulated to obtain wet granules; cross-linked methylcellulose sodium, silicon dioxide and magnesium stearate are mixed with the wet granules, and dried, granulated and tableted to obtain tablet cores; (2) Add water to the gastric-soluble coating premix to prepare a gastric-soluble coating solution, and spray the gastric-soluble coating solution evenly on the surface of the tablet core by spraying. After spraying, the tablet core is dried in an oven at a drying temperature of 40°C. (3) Add water to the enteric coating premix to prepare an enteric coating solution, and spray the enteric coating solution prepared by adding water onto the surface of the tablets that have been dried in step (2) by spraying, and finally perform fluidized bed drying again at a drying temperature of 35° C. After drying, erythromycin enteric-coated tablets are prepared.

[0025] Comparative Example 1 An erythromycin enteric-coated tablet, comprising a tablet core, an intermediate layer, an isolation layer and an enteric-coated layer; wherein, by weight, the tablet core contains 62 parts of erythromycin, 8 parts of microcrystalline cellulose, 1 part of povidone, 15 parts of water, 3 parts of sodium citrate, 2 parts of cross-linked povidone and 3 parts of hydroxypropyl cellulose; The middle layer contains 0.5 parts of cross-linked methylcellulose sodium, 0.3 parts of silicon dioxide and 0.3 parts of magnesium stearate; The isolation layer contains 8 parts of gastric soluble coating premix; the enteric layer contains 25 parts of enteric coating premix. The gastric soluble coating premix is ​​a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2:1; the enteric coating premix is ​​a mixture of hydroxypropyl methylcellulose phthalate, triethyl citrate and polyethylene glycol in a mass ratio of 5:1:0.5.

[0026] The preparation method of the erythromycin enteric-coated tablets described in Comparative Example 1 comprises the following specific steps: (1) According to the proportion of raw material components, erythromycin, microcrystalline cellulose, povidone, water, sodium citrate, crospovidone and hydroxypropyl cellulose are fully mixed and granulated to obtain wet granules; cross-linked methylcellulose sodium, silicon dioxide and magnesium stearate are mixed with the wet granules, and dried, granulated and tableted to obtain tablet cores; (2) Add water to the gastric soluble coating premix to prepare a gastric soluble coating solution, and spray the gastric soluble coating solution evenly on the surface of the tablet core by spraying. After spraying, perform fluidized bed drying at a drying temperature of 30°C. (3) Add water to the enteric coating premix to prepare an enteric coating solution, and spray the enteric coating solution prepared by adding water onto the surface of the tablets that have been dried in step (2) by spraying, and finally perform fluidized bed drying again at a drying temperature of 30° C. After drying, erythromycin enteric-coated tablets are prepared.

[0027] Dissolution test of erythromycin enteric-coated tablets Take the erythromycin enteric-coated tablets described in Examples 1 to 3 and Comparative Example 1, and test their dissolution, the specific steps are as follows: According to the provisions of the Chinese Pharmacopoeia, the basket method was selected for testing, the stirring rate was set to 100 rpm, and the medium volume was 900 mL. The test results are shown in Table 1.

[0028] Table 1 Dissolution test results

[0029] Referring to Table 1, we can see that the erythromycin enteric-coated tablets prepared by the preparation method of the present invention have stable drug release characteristics and can maintain good stability during storage.

[0030] The specific implementation of the present invention described above does not constitute a limitation on the protection scope of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. An erythromycin enteric-coated tablet, characterized in that: The tablet comprises a core, an intermediate layer, an isolation layer and an enteric layer; wherein, by weight, the core comprises 60 to 65 parts of erythromycin, 5 to 10 parts of microcrystalline cellulose, 2 to 5 parts of povidone, 15 to 30 parts of water, 0.5 to 5 parts of sodium citrate, 1 to 3 parts of cross-linked povidone and 1 to 3 parts of hydroxypropyl cellulose; The middle layer comprises 1 to 5 parts of cross-linked sodium methylcellulose, 0.3 to 0.5 parts of silicon dioxide and 0.2 to 0.5 parts of magnesium stearate; The isolation layer comprises 8 to 10 parts of a gastric-soluble coating premix; and the enteric layer comprises 25 to 40 parts of an enteric-soluble coating premix.

2. The erythromycin enteric-coated tablets according to claim 1, characterized in that: Calculated by weight, the tablet core comprises 62-65 parts of erythromycin, 8-10 parts of microcrystalline cellulose, 3-5 parts of povidone, 15-20 parts of water, 3-5 parts of sodium citrate, 2-3 parts of cross-linked povidone and 1-3 parts of hydroxypropyl cellulose.

3. The erythromycin enteric-coated tablets according to claim 2, characterized in that: The middle layer comprises 3 to 5 parts of cross-linked sodium methylcellulose, 0.3 to 0.5 parts of silicon dioxide and 0.3 to 0.5 parts of magnesium stearate.

4. The erythromycin enteric-coated tablets according to any one of claims 1 to 3, characterized in that The gastric soluble coating premix comprises hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2 to 3:

1.

5. The erythromycin enteric-coated tablets according to any one of claims 1 to 3, characterized in that The enteric coating premix comprises hydroxypropyl methylcellulose phthalate, triethyl citrate and polyethylene glycol in a mass ratio of 5-7:1-2:0.5-1.

6. The method for preparing erythromycin enteric-coated tablets according to any one of claims 1 to 5, characterized in that: The steps include: (1) According to the proportion of raw material components, erythromycin, microcrystalline cellulose, povidone, water, sodium citrate, crospovidone and hydroxypropyl cellulose are fully mixed and granulated to obtain wet granules; cross-linked methylcellulose sodium, silicon dioxide and magnesium stearate are mixed with the wet granules, and dried, granulated and tableted to obtain tablet cores; (2) Adding water to the gastric-soluble coating premix to prepare a gastric-soluble coating solution, spraying the gastric-soluble coating solution evenly on the surface of the tablet core by spraying, and drying after spraying; (3) Add water to the enteric coating premix to prepare an enteric coating solution, and spray the enteric coating solution prepared by adding water onto the surface of the tablets that have been dried in step (2) by spraying, and finally dry again.

7. The method for preparing erythromycin enteric-coated tablets according to claim 6, characterized in that: The drying process in step (2) is fluidized bed drying or oven drying.

8. The method for preparing erythromycin enteric-coated tablets according to claim 7, characterized in that: The drying temperature in step (2) is 30-40°C.

9. The method for preparing erythromycin enteric-coated tablets according to claim 6, characterized in that: The second drying in step (3) is carried out by fluidized bed drying or oven drying.

10. The method for preparing erythromycin enteric-coated tablets according to claim 7, characterized in that: The temperature for the second drying in step (3) is 30-50°C.

Images