CN112516099B - Gliclazide sustained release tablet and preparation method thereof - Google Patents

Gliclazide sustained release tablet and preparation method thereof Download PDF

Info

Publication number
CN112516099B
CN112516099B CN202011456700.3A CN202011456700A CN112516099B CN 112516099 B CN112516099 B CN 112516099B CN 202011456700 A CN202011456700 A CN 202011456700A CN 112516099 B CN112516099 B CN 112516099B
Authority
CN
China
Prior art keywords
gliclazide
tablet
sustained release
glyceryl behenate
release
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.)
Active
Application number
CN202011456700.3A
Other languages
Chinese (zh)
Other versions
CN112516099A (en
Inventor
李勇
袁波
邓艳斌
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GUANGDONG HUANAN PHARMACEUTICAL GROUP CO Ltd
Guangdong Zhongsheng Pharmaceutical Co Ltd
Original Assignee
GUANGDONG HUANAN PHARMACEUTICAL GROUP CO Ltd
Guangdong Zhongsheng Pharmaceutical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by GUANGDONG HUANAN PHARMACEUTICAL GROUP CO Ltd, Guangdong Zhongsheng Pharmaceutical Co Ltd filed Critical GUANGDONG HUANAN PHARMACEUTICAL GROUP CO Ltd
Priority to CN202011456700.3A priority Critical patent/CN112516099B/en
Publication of CN112516099A publication Critical patent/CN112516099A/en
Application granted granted Critical
Publication of CN112516099B publication Critical patent/CN112516099B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses a gliclazide sustained release tablet and a preparation method thereof, the sustained release tablet comprises gliclazide, glyceryl behenate, a hydrophilic material, a filling agent, a lubricating agent and a pharmaceutically acceptable auxiliary material, wherein the mass ratio of the gliclazide to the glyceryl behenate to the hydrophilic material is 1: (0.3-0.6): (0.8-1.2). The sustained release tablet has stable drug release rate, equivalent release rate to the original drug, simple preparation process and suitability for industrial mass production.

Description

Gliclazide sustained release tablet and preparation method thereof
Technical Field
The invention relates to the technical field of medicines, in particular to a gliclazide sustained-release tablet and a preparation method thereof.
Background
Diabetes is a metabolic disease characterized by hyperglycemia, which is caused by defects in insulin secretion or impaired biological action, or both. Hyperglycemia occurring in the long term of diabetes results in chronic damage to, and dysfunction of, various tissues, particularly the eyes, kidneys, heart, blood vessels, nerves. Over 9200 million adults in china have diabetes, and 1.5 million people are potential patients for diabetes, i.e., about 1 out of every 10 adults have diabetes, 90% of which are type 2 diabetes. At present, the treatment of type 2 diabetes mainly comprises insulin treatment, biguanide drug treatment, sulfonylurea drug treatment, thiazolidinedione treatment, drug treatment for reducing carbohydrate absorption, aldose reductase inhibitor treatment and the like.
Gliclazide, chemical name is 1- (3-azabicyclo [3,3,0 ]]Octyl) -3-p-toluenesulfonylurea, soluble in chloroform, slightly soluble in methanol, slightly soluble in ethanol, insoluble in water, of formula C 15 H 21 N 3 O 3 S, molecular weight 323.41, structural formula as follows:
Figure BDA0002829597460000011
gliclazide belongs to a second-generation sulfonylurea hypoglycemic agent, directly acts on islet beta cells, can recover the early phase secretion peak of insulin, and recovers the physiological secretion mode of insulin. Therefore, gliclazide controls postprandial blood glucose elevation and does not cause hyperinsulinemia. Gliclazide has good control effect on body weight, and can also obviously reduce triglyceride and cholesterol. Gliclazide is developed and developed by Schveya France, and is firstly marketed in France in 1972, tablets and capsules are taken as the main materials at present, and gliclazide sustained-release preparations are prepared by adding auxiliary materials of conventional sustained-release preparations into gliclazide, the proportion of the gliclazide sustained-release preparations can reach up to 40 percent. The matrix type sustained release tablet has the problems of nonuniform drug release, easy burst release or incomplete drug release, and the membrane controlled sustained release preparation has the problems of coating membrane aging, slow drug release after long-term placement and the like. And the water-insoluble characteristic of gliclazide increases uncertainty in the release process in the slow release process.
Glyceryl behenate is an esterified product obtained by esterifying behenic acid and glycerol, and can be used as a slow-release material in medicines. As a lipid slow-release matrix, glyceryl behenate is convenient to use, and can be suitable for various preparation processes such as direct tabletting, wet granulation, dry granulation and hot melt granulation, the drug release is realized through an insoluble matrix, the diffusion from the matrix is a main mechanism of the drug release, and the burst release effect of the drug can be avoided.
Chinese patent ZL201310136470.6, applied by guangdong petidi pharmaceutical industry ltd at 2013.04.18, discloses a gliclazide tablet, which is characterized in that: is prepared by directly tabletting gliclazide solid dispersion particles and pharmaceutically acceptable auxiliary materials; the gliclazide solid dispersion particle is prepared by the following method: heating citric acid and polyvinyl acetate in a hot-melting extruder for melting, then adding gliclazide for melting, and extruding and granulating the molten liquid, wherein the weight ratio of the gliclazide to the citric acid is 1.5-2, and the weight ratio of the gliclazide to the polyvinyl acetate is 1-5.
Chinese patent ZL201710652866.4, applied by 2017.08.02 of Zhejiang Congde pharmaceutical industry group, inc. The patent discloses a gliclazide sustained release tablet, which is prepared by uniformly mixing drug-loaded particles and pharmaceutically acceptable auxiliary materials and tabletting, and is characterized in that the drug-loaded particles are prepared by the following method: heating glyceryl behenate to 65-70 ℃ for melting, then adding meglumine in the heat preservation process for stirring uniformly, then adding gliclazide for stirring until melting, cooling for solidification, and granulating, wherein the mass ratio of the gliclazide to the glyceryl behenate to the meglumine is (1.5-4.5): (0.1-0.3).
Chinese patent CN201910992482.6, applied by shandong lu anti-medicine gmbh in 2019.10.18. The patent discloses a gliclazide tablet (II) characterized by being prepared from raw materials including gliclazide, diluent, binder, glyceryl behenate and lubricant by fluid granulation and tableting.
Although the prior art discloses gliclazide sustained release tablets, glyceryl behenate is adopted as a sustained release material, the existing preparation process basically adopts a hot melting technology, the melting point of gliclazide is about 165 ℃, the gliclazide is easily degraded at high temperature, in Chinese patent ZL201710652866.4, the addition of meglumine and the like is reported to reduce the low eutectic temperature of the gliclazide glyceryl behenate mixture, but excessive auxiliary materials are easily added to cause side effects, and the scheme is finally used and still adopts a melting method. In actual production, the hot melting technology is complex, and the use conditions are limited. Secondly, because the behenate is a material which is difficult to dissolve in water, the medicament is difficult to release completely within 12 hours. The behenic acid glyceride is a waxy material, the character is changed after melting, the sticking phenomenon is easily generated in tabletting, and due to the lower melting point of the behenic acid glyceride, the tablet core is easy to stick and punch due to heat generated in the tabletting process, the long-time continuous tabletting is not facilitated, and the amplification production is influenced.
Disclosure of Invention
In view of the defects of the prior art, the invention aims to provide a gliclazide sustained release tablet and a preparation method thereof, the gliclazide sustained release tablet has good sustained release effect, active ingredients are slowly released in vivo after a patient takes the tablet, the blood concentration is stable, and the gliclazide sustained release tablet has long-acting property. In addition, the gliclazide sustained release tablet is simple to prepare, can be obtained by one-step granulation, does not need to be prepared by a melt extrusion or melting method, and has no sticking phenomenon in the process of tabletting.
Specifically, the gliclazide sustained release tablet comprises gliclazide, glyceryl behenate, a hydrophilic material, a filling agent, a lubricating agent and a pharmaceutically acceptable auxiliary material, wherein the mass ratio of the gliclazide to the glyceryl behenate to the hydrophilic material is 1: (0.3-0.6): (0.8-1.2).
In the invention, the composition and mass ratio of the gliclazide, the glyceryl behenate and the hydrophilic material are important technical keys for realizing technical effects. In the scheme, because the gliclazide is a water-insoluble drug and the behenate is an insoluble lipid auxiliary material, the gliclazide is insoluble in water and ethanol and cannot swell. After the two are mixed with hydrophilic materials, the insoluble particles can be wrapped by the hydrophilic components, and water can rapidly permeate into the tablet core to ensure that the tablet core is disintegrated, so that the release speed of the glyceryl behenate is adjusted, and the glyceryl behenate can be stably released within 12 h. When the dosage of the glyceryl behenate is too large, the medicament can not be completely released or the medicament release time is too long, and the treatment effect can not be achieved after the medicament is taken by patients. When the dosage of the glyceryl behenate is too small, the phenomenon of large-dosage release of the medicine occurs at the initial release stage, the release is excessive, the dosage is too large after the patient takes the medicine, and serious adverse reaction or poisoning phenomenon can occur. The dosage of the hydrophilic material plays a role in regulating the release speed of the glyceryl behenate, and the dosage is too large, so that the medicament is released in advance, and the dosage is too small, so that the medicament is difficult to release completely. The complete release effect can be achieved only when the gliclazide, the glyceryl behenate and the hydrophilic material are in a proper mass ratio. More specifically, the inventor finds that the mass ratio of the gliclazide to the glyceryl behenate to the hydrophilic material is 1: (0.3-0.6): (0.8-1.2), preferably 1:0.5:1.0, is beneficial to realizing the optimization of the quality of the gliclazide sustained release tablet product.
The hydrophilic material is selected from polyethylene glycol series, preferably polyethylene glycol 4000, polyethylene glycol 3350 or polyethylene glycol 6000, most preferably polyethylene glycol 4000, and the molecular weight is selected to have the advantages that the hydrophilic material is a solid with better fluidity and is easy to uniformly mix, for the invention, glyceryl behenate and polyethylene glycol can play a coupling role, and the drug release time of the gliclazide sustained release tablet can be controlled within 12 hours.
In the present invention, the lubricant is one of the key factors to solve the sticking phenomenon during the tabletting process. The glyceryl behenate has low melting point, and is easy to cause sticking due to compression heat in the long-term tabletting process, and the polyethylene glycol is also easy to cause sticking due to softening of the compression heat, so that the sticking phenomenon can occur in the tabletting process by adopting the two direct-pressing auxiliary materials for powder direct-pressing process development, and the situation becomes more complicated due to the existence of the glyceryl behenate and the polyethylene glycol simultaneously, so that the tablet weight difference is larger, and therefore, the selection of a proper lubricant is of great importance for solving the sticking phenomenon. The inventors have found that the use of talc or magnesium stearate separately, even in an amount up to the maximum allowable amount, does not effectively solve the sticking problem, and that when a mixed lubricant is used, the effect is superior to that when a single lubricant is used, the sticking problem can be solved excellently. Specifically, the lubricant is a mixture of talcum powder and magnesium stearate, and the mass percentage of the lubricant in the pharmaceutical composition ranges from 1% to 15%. Preferably, the mass ratio of the talcum powder to the magnesium stearate is 2.5-3.
In the gliclazide sustained release tablet, the filler is selected from one or a mixture of more than two of lactose monohydrate, mannitol, anhydrous lactose and corn starch, and the mass percentage range of the filler in the pharmaceutical composition is 15-45%. The use amount of lactose monohydrate is increased, the compressibility of the granules is improved, but the disintegration time is prolonged while the hardness is improved; the corn starch consumption is reduced, and the disintegration time is also shortened. When the filler is in a proper ratio, the release rate at each time point can be increased to be within a predetermined range. Preferably, the filler is a mixture of lactose monohydrate and corn starch, the mass ratio of the lactose monohydrate to the corn starch is 2-2.5.
In the gliclazide sustained release tablet, pharmaceutically acceptable auxiliary materials comprise a binder and a disintegrant, wherein the binder is selected from one or a mixture of more than two of corn starch and pregelatinized starch, and the disintegrant is selected from one or a mixture of more than two of crospovidone and croscarmellose sodium. The mass percentage range of the adhesive in the pharmaceutical composition is 2-15%, and the mass percentage range of the disintegrant in the pharmaceutical composition is 0.1-5%.
Specifically, the invention also provides a gliclazide sustained release tablet, which comprises the following components:
Figure BDA0002829597460000041
Figure BDA0002829597460000051
the invention also provides a preparation process of the gliclazide sustained release tablet, which adopts a one-step granulation method, can improve the compressibility of granules, further reduce sticking and simultaneously ensure the feasibility of production amplification, and the process comprises the following steps:
1) Preparing pregelatinized starch slurry, slowly adding pregelatinized starch into water, stirring, and sieving;
2) Placing gliclazide, lactose, corn starch, glyceryl behenate and polyethylene glycol in a granulator, preheating raw materials and auxiliary materials, spraying slurry and granulating when the temperature of the materials reaches 40-42 ℃, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the materials is less than or equal to 50 ℃;
3) Granulating, adding pulvis Talci, croscarmellose sodium or crospovidone, mixing, adding magnesium stearate, and mixing;
4) And (5) punching and tabletting.
Compared with the prior art, the invention has the following outstanding advantages and beneficial effects:
1) The gliclazide and the glyceryl behenate are insoluble in water, the drug is difficult to completely release within 12h, and the gliclazide and the glyceryl behenate are simultaneously dispersed in a proper amount of hydrophilic materials, so that the gliclazide and the glyceryl behenate can be controlled to completely release within 12 h.
2) The glyceryl behenate and the polyethylene glycol are easy to generate sticking phenomenon in the tabletting process, and the sticking phenomenon generated in the tabletting process is solved by adding a proper lubricant.
3) The preparation method adopts one-step granulation, does not need to adopt a melt extrusion or melting method, has simple preparation process and is suitable for industrial mass production.
The present invention will be described in further detail with reference to examples, but the embodiments of the invention are not limited thereto.
Example 1
Prescription
Name(s) Amount (g) (in 1000 tablets)
Gliclazide 30.0
Glyceryl behenate 15.0
Polyethylene glycol 4000 30.0
Lactose monohydrate 23.5
Corn starch 11.3
Talcum powder 3.8
Magnesium stearate 1.5
Pregelatinized starch 8.0
Croscarmellose sodium 1.1
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuously stirring for 20min after adding, wherein the stirring speed is 500rpm (two paddles), and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, lactose monohydrate, corn starch, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating raw and auxiliary materials, and starting spraying granulation when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the material is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and croscarmellose sodium, mixing for 10min, and mixing at 8rpm; adding magnesium stearate, and mixing for 5min at the mixing speed of 8rpm;
6) The tablet is pressed by a punch die with the diameter of 7.0mm, and the hardness of the tablet is 30-50N.
Example 2
Prescription
Name (R) Dosage (g) (in 1000 tablets)
Gliclazide 30.0
Glyceryl behenate 9.0
Polyethylene glycol 4000 24.0
Lactose monohydrate 15.0
Corn starch 7.5
Talcum powder 1.5
Magnesium stearate 0.6
Pregelatinized starch 8.0
Croscarmellose sodium 1.1
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuing to stir for 20min after adding, and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, lactose monohydrate, corn starch, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating the raw and auxiliary materials, and starting spraying granulation when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the materials is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and croscarmellose sodium, mixing for 10min, and mixing at 8rpm; adding magnesium stearate, and mixing for 5min at 8rpm;
6) The tablet is pressed by a punch die with the diameter of 6.0mm, and the hardness of the tablet is 30-50N.
Example 3
Prescription
Figure BDA0002829597460000071
Figure BDA0002829597460000081
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuously stirring for 20min after adding, wherein the stirring speed is 500rpm (two paddles), and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, lactose monohydrate, corn starch, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating the raw and auxiliary materials, and starting spraying granulation when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the materials is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and croscarmellose sodium, mixing for 10min, and mixing at 8rpm; adding magnesium stearate, and mixing for 5min at the mixing speed of 8rpm;
6) The tablets are pressed by a punch with the diameter of 8.0mm, and the hardness of the tablets is 30-50N.
Example 4
Prescription
Figure BDA0002829597460000082
Figure BDA0002829597460000091
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuing to stir for 20min after adding, and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, anhydrous lactose, corn starch, glyceryl behenate and polyethylene glycol 6000 in a granulator, preheating the raw and auxiliary materials, and starting spraying granulation when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the material is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and croscarmellose sodium, mixing for 10min, and mixing at 8rpm; adding magnesium stearate, and mixing for 5min at the mixing speed of 8rpm;
6) The tablet is pressed by a punch die with the diameter of 7.0mm, and the hardness of the tablet is 30-50N.
Example 5
Prescription
Figure BDA0002829597460000092
Figure BDA0002829597460000101
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuously stirring for 20min after adding, wherein the stirring speed is 500rpm (two paddles), and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, lactose monohydrate, corn starch, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating the raw and auxiliary materials, and starting spraying granulation when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the material is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and crospovidone, mixing for 10min, and mixing at 8rpm; adding magnesium stearate, and mixing for 5min at 8rpm;
6) The tablet is pressed by a punch die with the diameter of 8.0mm, and the hardness of the tablet is 30-50N.
Comparative example 1
Prescription
Name (R) Dosage (g) (in 1000 tablets)
Gliclazide 30.0
Glyceryl behenate 6.0
Polyethylene glycol 4000 21.0
Lactose monohydrate 16.9
Corn starch 11.3
Talcum powder 3.0
Magnesium stearate 1.5
Pregelatinized starch 5.0
Croscarmellose sodium 1.1
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuing to stir for 20min after adding, and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, lactose monohydrate, corn starch, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating raw and auxiliary materials, and starting spraying granulation when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the materials is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and croscarmellose sodium, mixing for 10min, and mixing at 8rpm; adding magnesium stearate, and mixing for 5min at the mixing speed of 8rpm;
6) The tablets are pressed by a punch with the diameter of 6.0mm, and the hardness of the tablets is 30-50N.
Comparative example 2
Prescription
Name(s) Dosage (g) (in 1000 tablets)
Gliclazide 30.0
Glyceryl behenate 24.0
Polyethylene glycol 4000 42.0
Lactose monohydrate 29.3
Corn starch 11.3
Talcum powder 4.9
Magnesium stearate 1.5
Pregelatinized starch 9.0
Croscarmellose sodium 1.5
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuing to stir for 20min after adding, and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, lactose monohydrate, corn starch, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating the raw and auxiliary materials, and starting spraying granulation when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the material is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and croscarmellose sodium, mixing for 10min, and mixing at 8rpm; adding magnesium stearate, and mixing for 5min at 8rpm;
6) The tablet is pressed by a punch die with the diameter of 8.0mm, and the hardness of the tablet is 30-50N.
Comparative example 3
Prescription
Name(s) Dosage (g) (in 1000 tablets)
Gliclazide 30.0
Glyceryl behenate 15.0
Lactose monohydrate 23.5
Corn starch 11.3
Talcum powder 3.8
Magnesium stearate 1.5
Pregelatinized starch 5.0
Croscarmellose sodium 1.1
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuously stirring for 20min after adding, wherein the stirring speed is 500rpm (two paddles), and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, lactose monohydrate, corn starch and glyceryl behenate in a granulator, preheating the raw and auxiliary materials, and starting spraying granulation when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the materials is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and croscarmellose sodium, mixing for 10min, and mixing at 8rpm; adding magnesium stearate, and mixing for 5min at 8rpm;
6) The tablet is pressed by a punch die with the diameter of 6.0mm, and the hardness of the tablet is 30-50N.
Comparative example 4
Prescription
Name (R) Dosage (g) (in 1000 tablets)
Gliclazide 30.0
Glyceryl behenate 15.0
Polyethylene glycol 4000 30.0
Lactose monohydrate 23.5
Talcum powder 3.8
Pregelatinized starch 8.0
Croscarmellose sodium 1.1
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuously stirring for 20min after adding, wherein the stirring speed is 500rpm (two paddles), and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, lactose monohydrate, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating the raw and auxiliary materials, and starting spraying and granulating when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the material is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Granulating with a sieve of phi 1.5mm at a granulating frequency of 10Hz and 10.0Hz;
5) Adding talcum powder and croscarmellose sodium, mixing for 10min, and mixing at 8rpm;
6) The tablets are compressed by a punch with 7.0mm phi and have the hardness of 30-50N.
Comparative example 5
Prescription
Figure BDA0002829597460000131
Figure BDA0002829597460000141
The preparation process comprises the following steps:
1) Preparing 10% pregelatinized starch slurry, slowly adding the formula amount of pregelatinized starch into a beaker filled with the formula amount of purified water (room temperature), stirring while adding, continuing to stir for 20min after adding, and after stirring, sieving by a 30-mesh sieve for later use;
2) Placing gliclazide, corn starch, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating the raw and auxiliary materials, and starting spraying and granulating when the temperature of the materials reaches 40-42 ℃;
3) Spraying slurry and granulating, wherein the air inlet temperature is 70 +/-10 ℃, and the fan frequency is 25-30Hz; the temperature of the materials is less than or equal to 50 ℃, and the liquid supply speed is about 1.0kg/min; the atomization pressure is 0.3MPa respectively, and the moisture of the particles is controlled to be 2.0-4.0%;
4) Sieving with a sieve of phi 1.5mm at a frequency of 10Hz and 10.0Hz;
5) Adding magnesium stearate and croscarmellose sodium, mixing for 10min, and mixing at 8rpm;
6) The tablets are pressed by a punch with the diameter of 6.0mm, and the hardness of the tablets is 30-50N.
The properties of the gliclazide sustained release tablets obtained in examples 1 to 5 and comparative examples 1 to 5 are shown in table 1, and it is known that the gliclazide sustained release tablets obtained in examples 1 to 5 are white-like tablets, which have no blushing phenomenon and have good dispersion uniformity, while the gliclazide sustained release tablets obtained in comparative examples 1 to 2 are white-like tablets, which have no blushing phenomenon and have good dispersion uniformity, the gliclazide sustained release tablets obtained in comparative example 3 are white-like tablets, which have no blushing phenomenon but have poor dispersion uniformity, and analysis shows that the gliclazide sustained release tablets obtained in comparative example 3 lack polyethylene glycol, and cannot be uniformly mixed with glyceryl behenate, the gliclazide sustained release tablets obtained in comparative examples 4 to 5 have good dispersion uniformity and have blushing, and analysis shows that the problem of the blushing in the tabletting process cannot be solved by a single lubricant.
TABLE 1 Properties of gliclazide sustained release tablets in examples 1 to 5 and comparative examples 1 to 5
Sample (I) Traits Sticking phenomenon Uniformity of dispersion
Example 1 Off-white color Without sticking Qualified
Example 2 Off-white color Without sticking Qualified
Example 3 Off-white color Without sticking Qualified
Example 4 Off-white color Without sticking Qualified
Example 5 Off-white color Without sticking Qualified
Comparative example 1 Off-white color Without sticking Qualified
Comparative example 2 Off-white color Without sticking Qualified
Comparative example 3 Off-white color Without sticking Fail to be qualified
Comparative example 4 Off-white color Sticking punch Qualified
Comparative example 5 Off-white color Sticking punch Qualified
Example 6 in vitro release results of gliclazide sustained release tablets obtained in examples 1 to 5 and comparative examples 1 to 2
Taking a commercially available product gliclazide sustained release tablet (specification: 30 mg) purchased from Schuyvera pharmaceutical Co., ltd as reference; the self-made samples are gliclazide sustained-release tablets of examples 1-5 and comparative examples 1-2.
The determination method comprises the following steps: taking a sample, taking a test solution for diluting to scale with a dissolution medium according to a dissolution and release determination method (0931 second method of general rules of the four parts of 2020 edition of Chinese pharmacopoeia), wherein a release medium is 900mL of phosphate buffer solution with pH of 8.6, the rotation speed is 100r/min, operating according to the method, continuing operating according to the method for 12 hours, respectively taking 8mL of the solution (and simultaneously supplementing 8 mL) in 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h and 12h, filtering, precisely taking 5mL of subsequent filtrate, respectively putting the subsequent filtrate into 25mL measuring bottles, uniformly shaking to obtain the test solution.
The release amount of each tablet was calculated by UV-visible spectrophotometry (Tong rule 0401), and the results of the dissolution test are shown in Table 2.
Table 2 measurement results (%) of release rate of gliclazide sustained-release tablets
Figure BDA0002829597460000151
Figure BDA0002829597460000161
According to the measurement of the release rate in table 2, the release of the gliclazide sustained-release tablets prepared in examples 1 to 5 is basically consistent with that of the commercially available sample, and the gliclazide sustained-release tablet obtained in example 1 is the closest to that of the commercially available sample, and the analysis shows that the gliclazide sustained-release tablet prepared in the scope of the present technical scheme has the effect of slow and accurate release within 12 hours. The release of the gliclazide sustained release tablets prepared in the comparative examples 1 and 2 is inconsistent with that of a commercially available sample, specifically, the gliclazide sustained release tablets prepared in the comparative example 1 are basically and completely released within 6-8 h, the release speed is higher than that of the commercially available sample, analysis shows that the content of glyceryl behenate in the formula is lower, and an effective sustained release effect cannot be achieved, while the gliclazide sustained release tablets prepared in the comparative example 2 are too slow to be completely released within 12h, and do not achieve a good sustained release effect, and analysis shows that the content of glyceryl behenate in the formula is higher, so that the release is influenced. Therefore, only the gliclazide sustained release tablets prepared in the technical scheme have good sustained release effect. Therefore, the gliclazide sustained release tablet can effectively control the release of the active ingredient gliclazide, and the drug can not be released suddenly, thereby ensuring the safety and effectiveness of the drug and stable quality. The invention adopts glyceryl behenate as a slow release material, and adopts the hydrophilic material polyethylene glycol to effectively control the release of the gliclazide, thereby avoiding the phenomenon that the active ingredient is incompletely or suddenly released, ensuring the safety and effectiveness of the medicine and ensuring the stable quality.
Example 7 stability study
The stability tests of the gliclazide sustained-release tablets of examples 1 to 5 and the gliclazide sustained-release tablets prepared by the preparation method (melting method) of the chinese patent ZL201710652866.4 were respectively carried out, and the results are shown in the following table 3.
Table 3 stability test results of gliclazide sustained release tablets
Figure BDA0002829597460000162
Figure BDA0002829597460000171
As can be seen from table 3, in examples 1 to 5, the impurities of the gliclazide sustained release tablets did not increase significantly with time, and the release dissolution rate did not decrease, and the results show that the stability of the gliclazide sustained release tablets prepared by the present scheme is good. However, the gliclazide sustained-release tablet prepared by the preparation method in patent ZL201710652866.4 has a tendency that the dissolution rate becomes slow along with time although the impurities are not obviously increased, and analysis shows that by using a melting method, glyceryl behenate has a slow curing process after melting and solidifying, the internal structure of the glyceryl behenate has a changing process, and the dissolution and release performance of the glyceryl behenate is gradually weakened along with the time.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (2)

1. The gliclazide sustained release tablet is characterized by comprising the following components:
gliclazide 30.0 mg/tablet
15.0 mg/tablet of glyceryl behenate
Polyethylene glycol 4000.0 mg/tablet
Lactose monohydrate 23.5 mg/tablet
Corn starch 11.3 mg/tablet
Talcum powder 3.8 mg/tablet
Magnesium stearate 1.5 mg/tablet
Pregelatinized starch 8.0 mg/tablet
Croscarmellose sodium 1.1 mg/tablet.
2. The preparation method of the gliclazide sustained release tablet according to claim 1, characterized by comprising the steps of:
1) Preparing pregelatinized starch slurry, slowly adding pregelatinized starch into water, stirring, and sieving;
2) Placing gliclazide, lactose monohydrate, corn starch, glyceryl behenate and polyethylene glycol 4000 in a granulator, preheating the raw and auxiliary materials, spraying slurry for granulation when the temperature of the materials reaches 40-42 ℃, wherein the air inlet temperature is 70 +/-10 ℃, and the frequency of a fan is 25-30Hz; the material temperature is less than or equal to 50 ℃;
3) Granulating, adding pulvis Talci and croscarmellose sodium, mixing, adding magnesium stearate, and mixing;
4) Stamping and tabletting.
CN202011456700.3A 2020-12-11 2020-12-11 Gliclazide sustained release tablet and preparation method thereof Active CN112516099B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011456700.3A CN112516099B (en) 2020-12-11 2020-12-11 Gliclazide sustained release tablet and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011456700.3A CN112516099B (en) 2020-12-11 2020-12-11 Gliclazide sustained release tablet and preparation method thereof

Publications (2)

Publication Number Publication Date
CN112516099A CN112516099A (en) 2021-03-19
CN112516099B true CN112516099B (en) 2023-03-17

Family

ID=74999022

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011456700.3A Active CN112516099B (en) 2020-12-11 2020-12-11 Gliclazide sustained release tablet and preparation method thereof

Country Status (1)

Country Link
CN (1) CN112516099B (en)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103845299B (en) * 2012-12-07 2016-06-29 亚宝药业集团股份有限公司 A kind of slow releasing tablet treating cardiovascular disease and preparation method thereof
CN104274419A (en) * 2013-07-10 2015-01-14 广东省中药研究所 Trimetazidine hydrochloride sustained release tablet taking glyceryl behenate as framework material and preparation method of trimetazidine hydrochloride sustained release tablet
CN110585155A (en) * 2019-10-18 2019-12-20 山东鲁抗医药股份有限公司 Gliclazide tablet (II) and preparation method thereof
CN110917158B (en) * 2019-12-09 2022-04-12 济南精合医药科技有限公司 Gliclazide microporous membrane osmotic pump sustained-release tablet and preparation method thereof
CN111329841B (en) * 2020-03-04 2021-11-19 山东鲁抗医药集团赛特有限责任公司 Gliclazide sustained release tablet and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study;Alaa Mohamed Nazief等;《Int J Nanomedicine》;20200218;第15卷;全文 *

Also Published As

Publication number Publication date
CN112516099A (en) 2021-03-19

Similar Documents

Publication Publication Date Title
EP2029134B1 (en) Stabilized pharmaceutical compositions comprising fesoterodine
JP7551182B2 (en) Composition for oral sustained release of poorly soluble drugs and method for preparing same
CN101574323B (en) Migltol microcapsule tablet and preparation method thereof
CN112641742B (en) Sacubitril valsartan sodium sustained-release tablet and preparation method thereof
CN112022825A (en) Alvatripopa maleate tablet and preparation method thereof
CN110037994A (en) A kind of brufen quick-release and slow-release double-layer tablets and preparation method thereof
CN111329841B (en) Gliclazide sustained release tablet and preparation method thereof
CN103520128A (en) Pramipexole sustained-release tablet, preparation method and application thereof
WO2024125654A1 (en) Sustained-release epalrestat composition, method for preparing same, and use thereof
CN112494485B (en) Saxagliptin and metformin hydrochloride sustained-release tablet
CN107375224B (en) A kind of Gliclazide sustained-release tablet
CN112516099B (en) Gliclazide sustained release tablet and preparation method thereof
CN109010298B (en) Metformin and glipizide compound composition and preparation method thereof
CN111557920A (en) Lipoic acid-containing tablet and preparation method thereof
CN109646417B (en) Trimetazidine sustained release tablet and preparation method thereof
CN113116836A (en) Gliclazide sustained release tablet
CN110585155A (en) Gliclazide tablet (II) and preparation method thereof
CN100490808C (en) Gliquilone slow-releasing preparation
TW201904572A (en) Febuxostat controlled release composition and preparation method thereof
WO2022042645A1 (en) Oral sustained release composition of edaravone, preparation method, and application
CN111450069A (en) Metformin hydrochloride oral sustained-release tablet and preparation method thereof
CN112618501A (en) Voglibose tablet and preparation method thereof
CN112168796A (en) Controlled-release drug sustained-release preparation of biphasic sustained-release system and preparation method thereof
CN110859843A (en) Pharmaceutical composition for treating arteriosclerosis complicated with angina pectoris and preparation method thereof
TWI823471B (en) Sacubitril-valsartan sodium sustained release composition, preparation method and use thereof

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