Metronidazole tablet and preparation method thereof

Abstract

The invention discloses a metronidazole tablet and a preparation method thereof. The metronidazole tablet is prepared from the following components in parts by mass: 55 to 60 parts of metronidazole, 35 to 40 parts of a filling agent, 5 to 10 parts of sorbitol, 1 to 5 parts of povidone K30, 5 to 15 parts of an adhesive, 0.2 to 0.5 part of magnesium stearate and 2 to 6 parts of a coating agent. By using sorbitol and povidone K30 in the auxiliary materials, the brittleness of the tablet can be improved, and the hardness and stability of the tablet are improved, so that the tablet is not easy to break in the production and storage processes. In addition, the dissolution rate of the tablet can be improved through the synergistic effect of the sorbitol and the povidone K30, so that the bioavailability of the medicine is improved.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and in particular relates to a metronidazole tablet and a preparation method thereof. Background Art

[0002] Metronidazole is used to treat intestinal and extraintestinal amebiasis (such as amoebic liver abscess, pleural amebiasis, etc.). In addition, it can also be used to treat vaginal trichomoniasis, balantidiasis and cutaneous leishmaniasis, guinea worm infection, etc. At present, this drug is also widely used in the treatment of anaerobic infections.

[0003] As a widely used anti-infective drug, the market for metronidazole tablets is expected to grow moderately with the growth of global health needs and the improvement of medical services. Due to the occurrence of various infectious diseases, the demand for antibacterial drugs continues to grow. As an effective antibacterial drug, metronidazole tablets have significant therapeutic effects in the treatment of anaerobic infections, etc., so the market demand is stable. However, the hardness of existing metronidazole tablets is poor, which affects their friability, which may have a certain impact on the dissolution of the drug. Summary of the invention

[0004] In view of the shortcomings of the prior art, the primary purpose of the present invention is to provide a metronidazole tablet and a preparation method thereof, so as to solve the problems of poor hardness and poor solubility of the existing metronidazole tablets.

[0005] 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.

[0006] The purpose of the present invention is achieved through the following technical solutions: A metronidazole tablet is prepared from the following components in parts by weight: 55-60 parts of metronidazole, 35-40 parts of a filler, 5-10 parts of sorbitol, 1-5 parts of povidone K30, 5-15 parts of a binder, 0.2-0.5 parts of magnesium stearate and 2-6 parts of a coating agent.

[0007] Preferably, the metronidazole tablets are prepared from the following components in parts by weight: 55-60 parts of metronidazole, 38-40 parts of filler, 8-10 parts of sorbitol, 3-5 parts of povidone K30, 10-15 parts of binder, 0.2-0.5 parts of magnesium stearate and 3-6 parts of coating agent.

[0008] Preferably, the filler is a mixture of corn starch and calcium hydrogen phosphate.

[0009] Preferably, the mass ratio of corn starch to calcium hydrogen phosphate is 1-3:1.

[0010] Preferably, the binder is a 10 wt % aqueous solution of povidone K30.

[0011] Preferably, the coating agent is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2 to 3:1.

[0012] The preparation method of the metronidazole tablets comprises the following steps: (1) First, metronidazole, filler, sorbitol and povidone K30 are uniformly mixed according to the mass ratio to obtain a dry mix; (2) Adding a binder to the dry blend and performing wet granulation, drying and granulation after granulation, and finally adding magnesium stearate and performing tableting; (3) The coating agent is prepared into a coating liquid, and the tablets after tableting are coated to obtain metronidazole tablets.

[0013] Preferably, in step (2), the drying temperature is 50-60°C.

[0014] Preferably, in step (2), the drying step is performed until the moisture content of the sample is 1-3%.

[0015] Preferably, in step (3), the concentration of the coating solution is 15-25%.

[0016] Preferably, in step (3), the coating treatment is performed by fluidized bed coating or spray drying coating.

[0017] Compared with the prior art, the beneficial effects of the present invention include: The use of sorbitol and povidone K30 in the auxiliary materials of the present invention can improve the brittleness of the tablet, increase its hardness and stability, and make it difficult to break during production and storage. In addition, the synergistic effect of sorbitol and povidone K30 can improve the dissolution of the tablet, thereby improving the bioavailability of the drug. 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 A metronidazole tablet is prepared from the following components in parts by weight: 55 parts of metronidazole, 35 parts of a filler, 5 parts of sorbitol, 1 part of povidone K30, 5 parts of a binder, 0.2 parts of magnesium stearate and 2 parts of a coating agent.

[0020] The filler is a mixture of corn starch and calcium hydrogen phosphate in a ratio of 1:1; the binder is a 10wt% aqueous solution of povidone K30; and the coating agent is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2:1.

[0021] The preparation method of the metronidazole tablets comprises the following steps: (1) First, metronidazole, filler, sorbitol and povidone K30 are uniformly mixed according to the mass ratio to obtain a dry mix; (2) Add a binder to the dry blend, add an appropriate amount of water, and perform wet granulation. After granulation, dry at 50°C (dry to a sample moisture content of 1%), granulate, and finally add magnesium stearate for tableting. (3) The coating agent is prepared into a coating solution with a concentration of 15%, and the tablets after tableting are subjected to fluidized bed coating treatment to obtain metronidazole tablets.

[0022] Example 2 A metronidazole tablet is prepared from the following components in parts by weight: 55 parts of metronidazole, 38 parts of a filler, 8 parts of sorbitol, 3 parts of povidone K30, 10 parts of a binder, 0.2 parts of magnesium stearate and 3 parts of a coating agent.

[0023] The filler is a mixture of corn starch and calcium hydrogen phosphate in a ratio of 2:1; the binder is a 10wt% aqueous solution of povidone K30; and the coating agent is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2:1.

[0024] The preparation method of the metronidazole tablets comprises the following steps: (1) First, metronidazole, filler, sorbitol and povidone K30 are uniformly mixed according to the mass ratio to obtain a dry mix; (2) Add a binder to the dry blend, add an appropriate amount of water, and perform wet granulation. After granulation, dry at 55°C (dry to a sample moisture content of 2%), granulate, and finally add magnesium stearate for tableting. (3) The coating agent is prepared into a coating solution with a concentration of 20%, and the tablets after tableting are subjected to fluidized bed coating treatment to obtain metronidazole tablets.

[0025] Example 3 A metronidazole tablet is prepared from the following components in parts by weight: 60 parts of metronidazole, 40 parts of a filler, 10 parts of sorbitol, 5 parts of povidone K30, 15 parts of a binder, 0.5 parts of magnesium stearate and 6 parts of a coating agent.

[0026] The filler is a mixture of corn starch and calcium hydrogen phosphate in a ratio of 1:1; the binder is a 10wt% aqueous solution of povidone K30; and the coating agent is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2:1.

[0027] The preparation method of the metronidazole tablets comprises the following steps: (1) First, metronidazole, filler, sorbitol and povidone K30 are uniformly mixed according to the mass ratio to obtain a dry mix; (2) Add a binder to the dry blend, add an appropriate amount of water, and perform wet granulation. After granulation, dry at 60°C (dry to a sample moisture content of 1%), granulate, and finally add magnesium stearate for tableting. (3) The coating agent is prepared into a coating solution with a concentration of 15%, and the tablets after tableting are subjected to fluidized bed coating treatment to obtain metronidazole tablets.

[0028] Example 4 A metronidazole tablet is prepared from the following components in parts by weight: 58 parts of metronidazole, 35 parts of a filler, 8 parts of sorbitol, 5 parts of povidone K30, 10 parts of a binder, 0.5 parts of magnesium stearate and 6 parts of a coating agent.

[0029] The filler is a mixture of corn starch and calcium hydrogen phosphate in a ratio of 1:1; the binder is a 10wt% aqueous solution of povidone K30; and the coating agent is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 3:1.

[0030] The preparation method of the metronidazole tablets comprises the following steps: (1) First, metronidazole, filler, sorbitol and povidone K30 are uniformly mixed according to the mass ratio to obtain a dry mix; (2) Add a binder to the dry blend, add an appropriate amount of water, and perform wet granulation. After granulation, dry at 60°C (dry to a sample moisture content of 1%), granulate, and finally add magnesium stearate for tableting. (3) The coating agent is prepared into a coating solution with a concentration of 15%, and the tablets after tableting are subjected to fluidized bed coating treatment to obtain metronidazole tablets.

[0031] Comparative Example 1 A metronidazole tablet is prepared from the following components in parts by weight: 55 parts of metronidazole, 38 parts of a filler, 11 parts of sorbitol, 10 parts of a binder, 0.2 parts of magnesium stearate and 3 parts of a coating agent.

[0032] The filler is a mixture of corn starch and calcium hydrogen phosphate in a ratio of 2:1; the binder is a 10wt% aqueous solution of povidone K30; and the coating agent is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2:1.

[0033] The preparation method of the metronidazole tablets comprises the following steps: (1) First, metronidazole, filler, sorbitol and povidone K30 are uniformly mixed according to the mass ratio to obtain a dry mix; (2) Add a binder to the dry blend, add an appropriate amount of water, and perform wet granulation. After granulation, dry at 55°C (dry to a sample moisture content of 2%), granulate, and finally add magnesium stearate for tableting. (3) The coating agent is prepared into a coating solution with a concentration of 20%, and the tablets after tableting are subjected to fluidized bed coating treatment to obtain metronidazole tablets.

[0034] Comparative Example 2 A metronidazole tablet is prepared from the following components in parts by weight: 55 parts of metronidazole, 38 parts of a filler, 11 parts of povidone K30, 10 parts of a binder, 0.2 parts of magnesium stearate and 3 parts of a coating agent.

[0035] The filler is a mixture of corn starch and calcium hydrogen phosphate in a ratio of 2:1; the binder is a 10wt% aqueous solution of povidone K30; and the coating agent is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2:1.

[0036] The preparation method of the metronidazole tablets comprises the following steps: (1) First, metronidazole, filler, sorbitol and povidone K30 are uniformly mixed according to the mass ratio to obtain a dry mix; (2) Add a binder to the dry blend, add an appropriate amount of water, and perform wet granulation. After granulation, dry at 55°C (dry to a sample moisture content of 2%), granulate, and finally add magnesium stearate for tableting. (3) The coating agent is prepared into a coating solution with a concentration of 20%, and the tablets after tableting are subjected to fluidized bed coating treatment to obtain metronidazole tablets.

[0037] Dissolution Testing Take the metronidazole tablets prepared in Examples 1 to 4 and Comparative Examples 1 to 2, and test their dissolution, the specific steps are as follows: According to the first method of the second dissolution method of the Chinese Pharmacopoeia (2010 edition), Appendix XC: Use 900 mL of hydrochloric acid solution (9→1000) as the dissolution medium, the speed is 100 revolutions per minute, operate according to the law, take the solution for filtration at 10min, 20min, 30min, 40min and 60min, take the filtrate, and measure it according to the UV-visible spectrophotometry of the second appendix IVA of the Chinese Pharmacopoeia (2010 edition). The test results are shown in Table 1.

[0038] Table 1 Dissolution results

[0039] As can be seen from Table 1, the dissolution rate of the metronidazole tablets prepared by the preparation method of the present invention reached 84% to 88% at 20 minutes; while in Comparative Examples 1 and 2, the samples containing sorbitol or povidone K30 alone, although the dissolution rate at 20 minutes reached 80%, were still lower than the dissolution rate of the embodiment of the present invention. From a long-term perspective, the dissolution rate of the metronidazole tablets prepared by the embodiment of the present invention at 60 minutes was still higher than that of the comparative example. 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. A metronidazole tablet, characterized in that: The invention is prepared from the following components in parts by weight: 55-60 parts of metronidazole, 35-40 parts of a filler, 5-10 parts of sorbitol, 1-5 parts of povidone K30, 5-15 parts of a binder, 0.2-0.5 parts of magnesium stearate and 2-6 parts of a coating agent.

2. The metronidazole tablet according to claim 1, characterized in that: The metronidazole tablet is prepared from the following components in parts by weight: 55-60 parts of metronidazole, 38-40 parts of filler, 8-10 parts of sorbitol, 3-5 parts of povidone K30, 10-15 parts of binder, 0.2-0.5 parts of magnesium stearate and 3-6 parts of coating agent.

3. The metronidazole tablet according to claim 1 or 2, characterized in that: The filler is a mixture of corn starch and calcium hydrogen phosphate.

4. The metronidazole tablet according to claim 3, characterized in that: The mass ratio of the corn starch to calcium hydrogen phosphate is 1-3:

1.

5. The metronidazole tablet according to claim 1, characterized in that: The adhesive is a polyvidone K30 aqueous solution with a concentration of 10 wt%.

6. The metronidazole tablet according to claim 1, characterized in that: The coating agent is a mixture of hydroxypropyl methylcellulose and polyvinyl alcohol in a mass ratio of 2-3:

1.

7. The method for preparing the metronidazole tablets according to any one of claims 1 to 6, characterized in that: The steps include: (1) First, metronidazole, filler, sorbitol and povidone K30 are uniformly mixed according to the mass ratio to obtain a dry blend; (2) Adding a binder to the dry blend and performing wet granulation, drying and granulation after granulation, and finally adding magnesium stearate and performing tableting; (3) The coating agent is prepared into a coating liquid, and the tablets after tableting are coated to obtain metronidazole tablets.

8. The method for preparing metronidazole tablets according to claim 7, characterized in that: The drying temperature in step (2) is 50-60°C.

9. The method for preparing metronidazole tablets according to claim 8, characterized in that: The drying in (2) is drying until the water content of the sample is 1-3%; The concentration of the coating solution in (3) is 15-25%.

10. The method for preparing metronidazole tablets according to claim 7, characterized in that: The coating treatment method described in (3) is fluidized bed coating or spray drying coating.

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