CN110917161A - Metronidazole tablet and preparation method thereof - Google Patents
Metronidazole tablet and preparation method thereof Download PDFInfo
- Publication number
- CN110917161A CN110917161A CN201911406142.7A CN201911406142A CN110917161A CN 110917161 A CN110917161 A CN 110917161A CN 201911406142 A CN201911406142 A CN 201911406142A CN 110917161 A CN110917161 A CN 110917161A
- Authority
- CN
- China
- Prior art keywords
- metronidazole
- tablets
- tablet
- microns
- granules
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a metronidazole tablet and a preparation method thereof, wherein the preparation method comprises the following steps: crushing a metronidazole raw material, and sieving the crushed metronidazole raw material by a first sieve to obtain metronidazole, wherein the particle size of the metronidazole is not more than 300 microns; weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for granulation, and sieving by a second sieve to obtain wet granules, wherein the particle size of the filling agent is not more than 150 microns; drying the wet particles, finishing the particles, adding a lubricant, and mixing in a mixer to obtain intermediate particles; and tabletting, coating and packaging the intermediate granules to obtain the metronidazole tablets. The preparation method of the metronidazole tablets provided by the embodiment of the invention has stable process, ensures the product quality of the finally obtained metronidazole tablets, has better dissolution rate, effectively improves the dissolution effect, and improves the quality and curative effect of the metronidazole tablets.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a metronidazole tablet and a preparation method thereof.
Background
Metronidazole is a synthetic oral antiprotozoal and antibacterial agent that may exert antibacterial activity in anaerobic environments by the following mechanisms: after entering into the body, the medicine is acted by intracellular ion transport protein to form a concentration gradient for promoting the medicine to be transported into the cells. The drug forms free radicals within the cell, which in turn interact with intracellular components, ultimately leading to microbial death. The metronidazole has wide application and obvious curative effect on various pathogenic diseases:
(1) treatment of intestinal and parenteral amebiasis, such as peptic ulcers. Metronidazole is effective in treating peptic ulcer, improving gastric mucosa epithelial cell and its secretion function, and enhancing gastric mucosa barrier and mucus barrier.
(2) Treating respiratory diseases. Metronidazole is used for treating acute attack and empyema of chronic bronchitis.
(3) Can be used for treating hyperlipidemia. The metronidazole has quick response, short treatment course and small side effect when being used for treating hyperlipemia, and can be regarded as a quick-acting, effective and safe blood fat reducing medicine.
(4) Treating stomatological diseases. Metronidazole is used for treating chronic gingivitis, simple gingival bleeding, acute and chronic periapical periodontitis and periodontal disease, and becomes a novel medicine of stomatology.
(5) Treating gynecological diseases. Can be used for treating vaginitis, trichomonas vaginalis, and acute pelvic inflammatory disease. Metronidazole is an ideal medicine for treating gynecological infection.
(6) Treating dermatological diseases. External preparation containing metronidazole is used for treating folliculitis, acne, seborrheic dermatitis, scabies, rosacea, psoriasis, tinea pedis, papular urticaria, balanopathy, and cutaneous leishmaniasis. Metronidazole has good effect on various skin diseases, and may be related to the effects of killing parasite, resisting allergy and resisting anaerobic bacteria.
(7) Preventing and treating anaerobic bacteria infectious diseases. Because of strong anti-anaerobe effect, metronidazole can be used to treat infectious diseases caused by anaerobe of various systems, such as: septicemia, endocarditis, lower respiratory tract infection, intraperitoneal infection, central nervous system, bone joint and skin soft tissue infection, upper neck sinusitis, liver abscess, cholecystitis, chronic colitis, chronic prostatitis, etc. Meanwhile, the metronidazole can prevent the infection of the incision after the appendicitis operation, reduce the infection after the bone trauma and obviously prevent the abdominal cavity adhesion after the operation.
Metronidazole belongs to the class I drugs of BCS (Biopharmaceutics Classification System), namely high-solubility and high-permeability drugs, and the solubility of the metronidazole reaches 10mg/ml in the range of pH value 1-8, and the metronidazole belongs to the high-solubility drugs. However, the metronidazole preparations in the domestic market are mostly tablets and injections, wherein most enterprises of the tablets have earlier approval time, poor dissolution performance and limited quality and curative effect, so that the pharmaceutical effect is poor in clinical use.
Disclosure of Invention
The invention aims to overcome the defects in the prior art, provides a metronidazole tablet and a preparation method thereof, and aims to solve the technical problem that the conventional metronidazole tablet is not ideal in dissolution effect and poor in drug effect.
In order to achieve the purpose, the invention adopts the following technical scheme:
the embodiment of the invention provides a metronidazole tablet, which comprises the following components in percentage by mass, based on the total mass of the metronidazole tablet as 100%:
in one embodiment, the metronidazole tablets comprise the following components in percentage by mass:
in one embodiment, the metronidazole tablets comprise the following components in percentage by mass:
in one embodiment, the filler comprises one of dibasic calcium phosphate, microcrystalline cellulose, and corn starch;
and/or the disintegrant comprises one of starch, croscarmellose sodium, low substituted hydroxypropyl cellulose, and crospovidone;
and/or the binder comprises one of hydroxypropyl cellulose and povidone;
and/or the lubricant comprises one of magnesium stearate, calcium stearate and sodium hard fumarate.
In a second aspect of the embodiments of the present invention, there is provided a method for preparing metronidazole tablets as described above, including the following steps:
crushing a metronidazole raw material, and sieving the crushed metronidazole raw material by a first sieve to obtain metronidazole, wherein the particle size of the metronidazole is not more than 300 microns;
weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for granulation, and sieving by a second sieve to obtain wet granules, wherein the particle size of the filling agent is not more than 150 microns;
drying the wet particles, finishing the particles, adding a lubricant, and mixing in a mixer to obtain intermediate particles;
and tabletting, coating and packaging the intermediate granules to obtain the metronidazole tablets.
In one embodiment, the particle size of the metronidazole is no greater than 250 microns.
In one embodiment, the particle size of the metronidazole is controlled to D90 to be 200-250 microns.
In one embodiment, the metronidazole, the filler and the disintegrant are weighed according to the preset mass percentage and uniformly mixed in a wet granulator, and in the step of granulating the binder, the adding time of the binder is less than 5 minutes.
In one embodiment, the filler has a particle size of no greater than 100 microns.
In one embodiment, the filler has a particle size D90 of 50-70 microns.
In one embodiment, in the step of finishing the wet granules after drying, the drying temperature is not more than 60 ℃, and the moisture content of the granules of the wet granules after drying is 1.5-3%.
In one embodiment, in the step of adding the lubricant and then mixing in a mixer to obtain the intermediate particles, the mixing time in the mixer is 10-30 minutes.
In one embodiment, the intermediate granules are tableted, coated and packaged to obtain metronidazole tablets, comprising:
tabletting the intermediate particles after the content is reduced to obtain plain tablets;
coating the plain tablets in a coating machine to obtain coated tablets;
and packaging the coated tablets by adopting aluminum plastic to obtain the metronidazole tablets.
In one embodiment, in the step of tabletting after the reduced content of the intermediate particles, the tabletting hardness is controlled to be 6-8 kg.
In one embodiment, in the step of coating the plain tablets in a coating machine to obtain coated tablets, the weight of the plain tablets is increased by 1-2% after coating.
The metronidazole tablets and the preparation method thereof provided by the embodiment of the invention have the beneficial effects that: according to the preparation method of the metronidazole tablet provided by the embodiment of the invention, ingredients such as the filler, the disintegrant, the adhesive and the lubricant are added in the preparation process, the proportion of the metronidazole tablet, the filler, the disintegrant, the adhesive and the lubricant and the particle size of the metronidazole tablet and the filler are controlled, the whole preparation process is stable, the product quality of the finally obtained metronidazole tablet is ensured, the dissolution rate is better, the dissolution effect is effectively improved, and the quality and the curative effect of the metronidazole tablet are improved.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The embodiment of the invention provides a metronidazole tablet, which comprises the following components in percentage by mass, based on the total mass of the metronidazole tablet as 100%:
among other things, fillers may be used to fill the weight or volume of the tablet, thereby facilitating tableting. The structural formula of metronidazole is:
according to the metronidazole tablet provided by the embodiment of the invention, ingredients such as the filler, the disintegrant, the adhesive and the lubricant are added in the preparation process, and the proportion of the metronidazole tablet, the filler, the disintegrant, the adhesive and the lubricant and the particle size of the metronidazole tablet and the filler are controlled, so that the finally obtained metronidazole tablet has better dissolution rate, the dissolution effect is effectively improved, and the quality and curative effect of the metronidazole tablet are improved.
In this embodiment, the filler comprises one of calcium hydrogen phosphate, microcrystalline cellulose and corn starch, and is optionally calcium hydrogen phosphate; the disintegrating agent comprises one of starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose and crospovidone, and can be selected from corn starch; the binder comprises one of hydroxypropyl cellulose and polyvidone, and is selected from polyvidone; the lubricant comprises one of magnesium stearate, calcium stearate and sodium stearyl fumarate, and is selected from magnesium stearate.
Further, the metronidazole tablets comprise the following components in percentage by mass:
the metronidazole tablets with the content have better dissolution effect.
In one embodiment, the metronidazole tablets comprise the following components in percentage by mass:
in one embodiment, the metronidazole tablets comprise the following components in percentage by mass:
in one embodiment, the metronidazole tablets comprise the following components in percentage by mass:
in a second aspect of the embodiments of the present invention, there is provided a metronidazole tablet preparation method, including the following steps: step S10: the metronidazole raw material is crushed and sieved by a first sieve to obtain the metronidazole, wherein the particle size of the metronidazole is not more than 300 microns.
The mesh size of the first mesh may be set as required, and may be, for example, 60 mesh. After the metronidazole raw material is crushed, the particle size of the metronidazole raw material can be screened through a first sieve, so that the particle size of the obtained metronidazole is not more than 300 microns. On one hand, when the granularity of the raw material micro powder is too fine, the material is gathered, and the disintegration of the self-made product is influenced, so that the dissolution is influenced; on the other hand, when the particle size of the raw material micro powder is too large, the material has poor slicing effect. And the particle size of the metronidazole is controlled to be not more than 300 microns, so that the raw materials can be dispersed and do not aggregate into lumps.
Optionally, the particle size of metronidazole is no greater than 250 microns, resulting in better dispersion. For example, the grain size of metronidazole is controlled to be D90(D90 is the grain size corresponding to 90% of the cumulative grain size distribution of a sample, the grain size is greater than 10% of the particles and less than 90% of the particles), and is 200-250 microns, of course, other values are possible, and the value is not limited herein.
Step S20: weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for granulation, and sieving by a second sieve to obtain wet granules, wherein the particle size of the filling agent is not more than 150 microns.
The preset mass ratio is the mass percentage content of each component included in the metronidazole tablets, for example, based on 100% of the total mass of the metronidazole tablets, the mass percentage content of the metronidazole tablets is as follows:
wherein the filler comprises one of calcium hydrogen phosphate, microcrystalline cellulose and corn starch, and is selected from calcium hydrogen phosphate; the disintegrating agent comprises one of starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose and crospovidone, and can be selected from corn starch; the binder comprises one of hydroxypropyl cellulose and polyvidone, and is selected from polyvidone; the lubricant comprises one of magnesium stearate, calcium stearate and sodium stearyl fumarate, and is selected from magnesium stearate.
In one embodiment, the metronidazole tablets comprise the following components in percentage by mass based on 100% of the total mass of the metronidazole tablets:
when the wet granules are prepared, the metronidazole, the filling agent and the disintegrating agent are weighed according to the weight ratio and mixed in a wet granulator, and the adding time of the adhesive is controlled to be less than 5 minutes in the mixing process, so that the uniform mixing can be ensured.
Furthermore, the particle size of the filler is not more than 100 microns, for example, the particle size of the filler is controlled to be D90 to be 50-70 microns, so that the subsequent tabletting is facilitated, and the dissolving effect of the metronidazole tablet is improved. The mesh number of the second mesh sieve can be set according to the requirement, for example, the mesh number can be 20 meshes, so that the particle size of the obtained wet particles can meet the requirement, and the dissolving effect of the metronidazole tablets can be guaranteed.
Step S30: and drying the wet granules, finishing the granules, adding a lubricant, and mixing in a mixer to obtain intermediate granules.
When the wet granules are dried, the drying temperature does not exceed 60 ℃, and the drying time is controlled, so that the moisture content in the dried granules is 1.5-3%, for example, the moisture content can be 2.5%. The granules need to be sized after being dried, and an appropriate amount of lubricant needs to be added in the sizing process and is put into a three-dimensional mixer for mixing so as to ensure better sizing effect. The mixing time is 10 to 30 minutes, for example, 10 minutes, and uniform mixing can be ensured.
Step S40: and tabletting, coating and packaging the intermediate granules to obtain the metronidazole tablets.
In order to obtain metronidazole tablets, the steps of tabletting and the like are required to be carried out on the obtained intermediate granules. In this embodiment, step S40 may include the following steps:
step S401: and (3) converting the content of the intermediate particles, and tabletting to obtain plain tablets. In the tabletting process, the tabletting hardness is controlled to be 6-8 kg, and good tabletting is ensured.
Step S402: and (3) coating the plain tablets in a coating machine to obtain coated tablets. When coating is carried out, coating powder with the mark number of 03B690003-CN is prepared firstly, and then the coating powder is used for coating the plain tablets in a coating machine. In the coating process, the weight of the coating is controlled to be increased by 1-2%, namely the weight of the coated tablet is 1-2% of that of the plain tablet.
Step S403: and packaging the coated tablets by adopting aluminum plastic to obtain the metronidazole tablets.
According to the preparation method of the metronidazole tablet provided by the embodiment of the invention, ingredients such as the filler, the disintegrant, the adhesive and the lubricant are added in the preparation process, the proportion of the metronidazole tablet, the filler, the disintegrant, the adhesive and the lubricant and the particle size of the metronidazole tablet and the filler are controlled, the whole preparation process is stable, the product quality of the finally obtained metronidazole tablet is ensured, the dissolution rate is better, the dissolution effect is effectively improved, and the quality and the curative effect of the metronidazole tablet are improved.
The preferred steps of the metronidazole tablet preparation method provided by the embodiment of the invention are as follows:
step S501: the metronidazole raw material is crushed and sieved by a 60-mesh sieve to obtain the metronidazole, wherein the particle size of the metronidazole is 200-250 microns.
Step S502: weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for less than 5 minutes, granulating, and sieving with a 20-mesh sieve to obtain wet granules, wherein the particle size of the filling agent is 50-70 microns.
Step S503: drying the wet granules, wherein the drying temperature is not more than 60 ℃, and the moisture of the dried granules is 2.5%.
Step S504: and drying the wet granules, finishing the granules, adding a lubricant, and mixing in a three-dimensional mixer for 10 minutes to obtain intermediate granules.
Step S505: and (3) tabletting the intermediate particles after the content is converted, and controlling the tabletting hardness to be 6-8 kg to obtain the plain tablets.
Step S506: and (3) putting the plain tablets into a coating machine, and coating with coating powder of 03B690003-CN to obtain coated tablets, wherein the weight of the coated tablets is increased by 1-2%.
Step S507: and packaging the coated tablets by adopting aluminum plastic to obtain metronidazole tablets.
The invention is described in further detail with reference to a part of the test results, which are described in detail below with reference to specific examples.
Example 1
Metronidazole is not crushed and sieved, D90 is about 300 microns, and D90 of calcium hydrogen phosphate is about 200 microns.
The metronidazole tablets comprise the following components in percentage by mass based on 100% of the total mass of the metronidazole tablets:
the preparation method of the metronidazole tablets comprises the following steps:
step S601: taking metronidazole as a raw material for later use.
Step S602: weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for less than 5 minutes, granulating, and sieving with a 20-mesh sieve to obtain wet granules, wherein the particle size of the filling agent is 200 microns.
Step S603: drying the wet granules, wherein the drying temperature is not more than 60 ℃, and the moisture of the dried granules is 2.5%.
Step S604: and drying the wet granules, finishing the granules, adding a lubricant, and mixing in a three-dimensional mixer for 10 minutes to obtain intermediate granules.
Step S605: and (3) tabletting the intermediate particles after the content is converted, and controlling the tabletting hardness to be 6-8 kg to obtain the plain tablets.
Step S606: and (3) putting the plain tablets into a coating machine, and coating with coating powder of 03B690003-CN to obtain coated tablets, wherein the weight of the coated tablets is increased by 1.62%.
Step S607: and packaging the coated tablets by adopting aluminum plastic to obtain metronidazole tablets.
Example 2
Metronidazole is not crushed and sieved, D90 is about 250 microns, and D90 of calcium hydrogen phosphate is about 120 microns.
The metronidazole tablets comprise the following components in percentage by mass based on 100% of the total mass of the metronidazole tablets:
the preparation method of the metronidazole tablets comprises the following steps:
step S701: the metronidazole raw material is crushed and sieved by a 60-mesh sieve for standby.
Step S702: weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for less than 5 minutes, granulating, and sieving with a 20-mesh sieve to obtain wet granules, wherein the particle size of the filling agent is 200 microns.
Step S703: drying the wet granules, wherein the drying temperature is not more than 60 ℃, and the moisture of the dried granules is 2.6%.
Step S704: and drying the wet granules, finishing the granules, adding a lubricant, and mixing in a three-dimensional mixer for 15 minutes to obtain intermediate granules.
Step S705: and (3) tabletting the intermediate particles after the content is converted, and controlling the tabletting hardness to be 6-8 kg to obtain the plain tablets.
Step S706: and (3) putting the plain tablets into a coating machine, and coating with coating powder of 03B690003-CN to obtain coated tablets, wherein the weight of the coated tablets is increased by 1.71%.
Step S707: and packaging the coated tablets by adopting aluminum plastic to obtain metronidazole tablets.
Example 3
Metronidazole is not crushed and sieved, D90 is about 220 microns, and D90 of calcium hydrogen phosphate is about 60 microns.
The metronidazole tablets comprise the following components in percentage by mass based on 100% of the total mass of the metronidazole tablets:
the preparation method of the metronidazole tablets comprises the following steps:
step S801: the metronidazole raw material is crushed and sieved by a 60-mesh sieve for standby.
Step S802: weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for less than 5 minutes, granulating, and sieving with a 20-mesh sieve to obtain wet granules, wherein the particle size of the filling agent is 200 microns.
Step S803: drying the wet granules, wherein the drying temperature is not more than 60 ℃, and the moisture of the dried granules is 2.3%.
Step S804: and drying the wet granules, finishing the granules, adding a lubricant, and mixing in a three-dimensional mixer for 20 minutes to obtain intermediate granules.
Step S805: and (3) tabletting the intermediate particles after the content is converted, and controlling the tabletting hardness to be 6-8 kg to obtain the plain tablets.
Step S806: and (3) putting the plain tablets into a coating machine, and coating with coating powder of 03B690003-CN to obtain coated tablets, wherein the weight of the coated tablets is increased by 1.38%.
Step S807: and packaging the coated tablets by adopting aluminum plastic to obtain metronidazole tablets.
Example 4
Metronidazole is not crushed and sieved, D90 is about 150 microns, and D90 of calcium hydrogen phosphate is about 38 microns.
The metronidazole tablets comprise the following components in percentage by mass based on 100% of the total mass of the metronidazole tablets:
the preparation method of the metronidazole tablets comprises the following steps:
step S901: the metronidazole raw material is crushed and sieved by a 60-mesh sieve for standby.
Step S902: weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for less than 5 minutes, granulating, and sieving with a 20-mesh sieve to obtain wet granules, wherein the particle size of the filling agent is 200 microns.
Step S903: drying the wet granules, wherein the drying temperature is not more than 60 ℃, and the moisture of the dried granules is 2.3%.
Step S904: and drying the wet granules, finishing the granules, adding a lubricant, and mixing in a three-dimensional mixer for 20 minutes to obtain intermediate granules.
Step S905: and (3) tabletting the intermediate particles after the content is converted, and controlling the tabletting hardness to be 6-8 kg to obtain the plain tablets.
Step S906: and (3) putting the plain tablets into a coating machine, and coating with coating powder of 03B690003-CN to obtain coated tablets, wherein the weight of the coated tablets is increased by 1.38%.
Step S907: and packaging the coated tablets by adopting aluminum plastic to obtain metronidazole tablets.
Control formulation
Metronidazole tablets;
the manufacturer: famar Health Care Services Madrid, s.a.u.
Trade name: FLAGYL
The certificate holder: winthrop Pharmaceuticals UK Limited/Zentiva/Aventis PharmaLimited/Sanofi
The european union is marketed in the united kingdom as the marketed country and spanish as the origin.
Dissolution tests were performed on examples 1 to 4 and the control formulation.
Dissolution was determined by reference to the dissolution and release assay (first method of general rule 0931).
The instrument comprises the following steps: ultraviolet spectrophotometer and dissolution rate tester
Dissolution medium: pH1.0 hydrochloric acid solution, pH4.5 buffer solution, pH6.8 buffer solution.
Volume of dissolution medium: 500ml of
Rotating speed: 100 revolutions per minute
Sampling time: 5min, 10min, 15min, 20min, 30min, 45min, 60min
Taking the product, measuring dissolution and release according to determination method (0931 first method of the four parts of the Chinese pharmacopoeia 2015 edition), taking hydrochloric acid solution with pH1.0, buffer solution with pH4.5 and buffer solution with pH6.8 as dissolution medium, rotating at 100 rpm, collecting solution after 30min, filtering, precisely measuring filtrate 3ml, placing in 50ml measuring flask, diluting with dissolution medium to scale, shaking, measuring absorbance at 277nm according to ultraviolet-visible spectrophotometry (0401 of the four parts of the Chinese pharmacopoeia 2015 edition), and measuring absorbance at C6H9N3O3The absorption coefficient (E1% 1cm) of (D) was 377, and the amount of elution was calculated for each tablet.
The results of the dissolution profile measurements are shown in tables 1 to 3 below.
| Time (min) | 5 | 10 | 15 | 20 | 30 | 45 | 60 | |
| Control formulation | Control formulation (%) | 30.5 | 86.1 | 97.2 | 98.4 | 98.2 | 98.4 | 99.4 |
| Example 1 | From preparation (%) | 25.1 | 50.5 | 70.6 | 78.3 | 82.3 | 87.0 | 90.6 |
| Example 2 | From preparation (%) | 28.1 | 61.3 | 78.4 | 84.1 | 87.8 | 95.4 | 99.5 |
| Example 3 | From preparation (%) | 33.2 | 82.1 | 95.1 | 98.6 | 99.2 | 99.3 | 99.3 |
| Example 4 | From preparation (%) | 35.5 | 76.2 | 81.1 | 85.2 | 86.4 | 87.7 | 89.8 |
TABLE 1 test results of dissolution curves in hydrochloric acid solution of pH1.0
| Time (min) | 5 | 10 | 15 | 20 | 30 | 45 | 60 | |
| Control formulation | Control formulation (%) | 14.4 | 63.6 | 88.3 | 93.1 | 98.4. | 99.1 | 99.3 |
| Example 1 | From preparation (%) | 15.1 | 42.5 | 56.6 | 70.3 | 78.3 | 80.0 | 82.6 |
| Example 2 | From preparation (%) | 16.6 | 53.6 | 70.4 | 83.1 | 84.4. | 90.1 | 95.3 |
| Example 3 | From preparation (%) | 16.2 | 57.7 | 87.8 | 95.3 | 99.2 | 99.4 | 99.9 |
| Example 4 | From preparation (%) | 17.2 | 56.4 | 75.1 | 80.5 | 82.4 | 84.3 | 84.9 |
TABLE 2 results of the test of dissolution curves in hydrochloric acid solution of pH4.5
TABLE 3 results of the test of dissolution curves in hydrochloric acid solution of pH6.8
Wherein RSD is dissolution within batch homogeneity. In a medium with pH6.8, the 10min dissolution behavior RSD of the examples 1 to 4 is less than 20 percent, and the 20min dissolution behavior RSD is less than 10 percent. As can be seen from tables 1 to 3, the dissolution rate of the metronidazole tablets prepared by the method provided by this embodiment can reach the dissolution effect of the control preparation, and has good similarity to the control preparation.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (15)
1. The metronidazole tablet is characterized by comprising the following components in percentage by mass based on 100% of the total mass of the metronidazole tablet:
2. the metronidazole tablet of claim 1, wherein the metronidazole tablet comprises the following components in mass percent:
3. the metronidazole tablet of claim 1, wherein the metronidazole tablet comprises the following components in mass percent:
4. the metronidazole tablet of any of claims 1 to 3, wherein the filler comprises one of dibasic calcium phosphate, microcrystalline cellulose and corn starch;
and/or the disintegrant comprises one of starch, croscarmellose sodium, low substituted hydroxypropyl cellulose, and crospovidone;
and/or the binder comprises one of hydroxypropyl cellulose and povidone;
and/or the lubricant comprises one of magnesium stearate, calcium stearate and sodium hard fumarate.
5. A metronidazole tablet preparation method as claimed in any of claims 1 to 4, characterised by the steps of:
crushing a metronidazole raw material, and sieving the crushed metronidazole raw material by a first sieve to obtain metronidazole, wherein the particle size of the metronidazole is not more than 300 microns;
weighing metronidazole, a filling agent and a disintegrating agent according to a preset mass percentage, uniformly mixing in a wet granulator, adding an adhesive for granulation, and sieving by a second sieve to obtain wet granules, wherein the particle size of the filling agent is not more than 150 microns;
drying the wet particles, finishing the particles, adding a lubricant, and mixing in a mixer to obtain intermediate particles;
and tabletting, coating and packaging the intermediate granules to obtain the metronidazole tablets.
6. The method for preparing metronidazole tablets as claimed in claim 5, where the particle size of the metronidazole is not greater than 250 microns.
7. The method for preparing metronidazole tablets as claimed in claim 6, characterised in that the particle size of metronidazole is controlled at D90 of 200-250 microns.
8. The metronidazole tablet preparation method of claim 5, wherein the metronidazole, the filler and the disintegrant are weighed according to the preset mass percentage and mixed evenly in a wet granulator, and in the step of adding the binder, the adding time of the binder is less than 5 minutes.
9. The method for preparing metronidazole tablets as claimed in claim 5 where the filler has a particle size not greater than 100 microns.
10. The metronidazole tablet of claim 9, wherein the filler has a particle size D90 of 50-70 microns.
11. The metronidazole tablet preparation method of claim 5 wherein in the granulating step after drying the wet granules, the drying temperature is not more than 60 ℃, and the moisture content of the granules of the wet granules after drying is 1.5% to 3%.
12. The metronidazole tablet preparation method of claim 5, wherein in the step of adding the lubricant and then mixing in a mixer to obtain the intermediate particles, the mixing time in the mixer is 10-30 minutes.
13. The metronidazole tablet preparation method of any one of claims 5 to 12, wherein the tabletting, coating and packaging of the intermediate granules to obtain metronidazole tablets comprises:
tabletting the intermediate particles after the content is reduced to obtain plain tablets;
coating the plain tablets in a coating machine to obtain coated tablets;
and packaging the coated tablets by adopting aluminum plastic to obtain the metronidazole tablets.
14. The metronidazole tablet preparation method of claim 12, wherein in the tabletting step after the reduced content of the intermediate particles, the tabletting hardness is controlled to 6-8 kg.
15. The metronidazole tablet preparation method of claim 12, wherein in the step of coating the plain tablets in a coating machine to obtain coated tablets, the weight of the plain tablets is increased by 1-2% after coating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911406142.7A CN110917161B (en) | 2019-12-31 | 2019-12-31 | Metronidazole tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911406142.7A CN110917161B (en) | 2019-12-31 | 2019-12-31 | Metronidazole tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110917161A true CN110917161A (en) | 2020-03-27 |
| CN110917161B CN110917161B (en) | 2022-04-05 |
Family
ID=69861575
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911406142.7A Active CN110917161B (en) | 2019-12-31 | 2019-12-31 | Metronidazole tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110917161B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111728972A (en) * | 2020-07-30 | 2020-10-02 | 迪沙药业集团有限公司 | Metronidazole vitamin B6 composition |
| CN113827572A (en) * | 2021-11-17 | 2021-12-24 | 华中药业股份有限公司 | Metronidazole particle and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104887636A (en) * | 2015-06-16 | 2015-09-09 | 吉林万通药业集团郑州万通复升药业股份有限公司 | Metronidazole tablet and preparation method thereof |
| CN106137988A (en) * | 2016-01-14 | 2016-11-23 | 上海信谊万象药业股份有限公司 | A kind of metronidazole solid preparation and preparation method thereof |
| CN109620813A (en) * | 2019-02-21 | 2019-04-16 | 武汉同济现代医药科技股份有限公司 | A kind of oral solid tablet and preparation method thereof containing metronidazole |
-
2019
- 2019-12-31 CN CN201911406142.7A patent/CN110917161B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104887636A (en) * | 2015-06-16 | 2015-09-09 | 吉林万通药业集团郑州万通复升药业股份有限公司 | Metronidazole tablet and preparation method thereof |
| CN106137988A (en) * | 2016-01-14 | 2016-11-23 | 上海信谊万象药业股份有限公司 | A kind of metronidazole solid preparation and preparation method thereof |
| CN109620813A (en) * | 2019-02-21 | 2019-04-16 | 武汉同济现代医药科技股份有限公司 | A kind of oral solid tablet and preparation method thereof containing metronidazole |
Non-Patent Citations (2)
| Title |
|---|
| 王沛主编: "《制药原理与设备》", 31 March 2014, 上海科学技术出版社 * |
| 胡英主编: "《药物制剂 第2版》", 28 February 2013, 中国医药科技出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111728972A (en) * | 2020-07-30 | 2020-10-02 | 迪沙药业集团有限公司 | Metronidazole vitamin B6 composition |
| CN111728972B (en) * | 2020-07-30 | 2023-05-16 | 迪沙药业集团有限公司 | Metronidazole vitamin B6 composition |
| CN113827572A (en) * | 2021-11-17 | 2021-12-24 | 华中药业股份有限公司 | Metronidazole particle and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110917161B (en) | 2022-04-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103655539B (en) | A kind of oral solid formulation of canagliflozin and preparation method thereof | |
| CN110917161B (en) | Metronidazole tablet and preparation method thereof | |
| CN112190559B (en) | Controlled-release folic acid tablet and preparation method thereof | |
| CN102078323A (en) | Minodronate-containing pharmaceutical composition | |
| CN104586804A (en) | Preparation method for letrozole tablets with good stability | |
| CN103263395A (en) | Telmisartan tablet preparation and preparation method thereof | |
| CN109481412A (en) | A kind of II crystal linezolid piece and its preparation process | |
| CN103417503A (en) | Amoxicillin potassium clavulanate tablet and preparation technology thereof | |
| CN106580898B (en) | A kind of erigeron breviscapus dispersion tablet and preparation method | |
| CN104523628A (en) | Succinic acid solifenacin tablet capable of achieving direct powder compression and preparation method of succinic acid solifenacin tablet | |
| CN104173310A (en) | Stable amoxicillin tablet composition, as well as preparation method and application thereof | |
| CN103463082A (en) | Telmisartan-amlodipine double-layer tablet and preparation method thereof | |
| CN100415230C (en) | Dispersion tablets of penicillin V potassium, and its preparing method | |
| CN110960501B (en) | Norfloxacin capsule and preparation method thereof | |
| CN104324013B (en) | The preparation technology of indapamide slow release agent | |
| CN109730969B (en) | Lactic acid levofloxacin dispersible tablet and preparation method thereof | |
| CN111358795A (en) | Tofacitinib citrate preparation and preparation method thereof | |
| CN104337783B (en) | A kind of capecitabine tablet and preparation method thereof | |
| CN104352465A (en) | Prucalopride succinate pharmaceutical composition free of silicon dioxide and preparation method of prucalopride succinate pharmaceutical composition | |
| CN105193758A (en) | Gliclazide sustained release tablets and preparation method thereof | |
| CN112007002B (en) | Metronidazole tablet composition with stable quality and preparation method thereof | |
| CN113116840B (en) | Preparation method of hydroxychloroquine sulfate tablet | |
| CN101658502A (en) | Metronidazole sustained-release tablets and preparation method thereof | |
| CN107898787B (en) | A kind of pharmaceutical composition and its preparation and preparation method | |
| CN105395503B (en) | A kind of Compound Chlorzoxazone dispersible tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |