CN110051639A - A kind of fater disintegration type nicergoline tablets and preparation method thereof - Google Patents
A kind of fater disintegration type nicergoline tablets and preparation method thereof Download PDFInfo
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- CN110051639A CN110051639A CN201910196333.9A CN201910196333A CN110051639A CN 110051639 A CN110051639 A CN 110051639A CN 201910196333 A CN201910196333 A CN 201910196333A CN 110051639 A CN110051639 A CN 110051639A
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
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- 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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- 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
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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Abstract
The present invention relates to a kind of preparation methods of fater disintegration type nicergoline tablets, this method includes a necessary committed step: preparing microcrystalline cellulose-carmethose particle first using wet granulation method, it is mixed again with other auxiliary materials, which can make the nicergoline tablets fater disintegration of preparation.Tablet forming technique provided by the invention is powder vertical compression technique: the microcrystalline cellulose of preparation-carmethose particle, Nicergoline, calcium monohydrogen phosphate, magnesium stearate are directly mixed；Tabletting, coating and aluminum-plastic packaged again, obtain finished product.Nicergoline tablets prepared by the present invention, every test rating is qualified, disintegration time limited≤2 minute, and dissolution rapidly is realized in the quick and complete disintegration of energy in the dissolution medium of investigation.Disintegrating agent easy to moisture absorption, the nicergoline tablets excellent in stability of preparation are not used in prescription provided by the invention.The preparation method of nicergoline tablets provided by the invention, method are novel, simple process, and good to solve the problems, such as that the nicergoline tablets listed at present are not disintegrated poor with stability.
Description
Technical field
The invention belongs to technical field of medicine, are related to a kind of preparation method of fater disintegration matrix agent, and in particular to
The preparation method of fater disintegration type nicergoline tablets.
Background technique
With the aging of population of society, memory and cognitive decline are the inevitable physiological phenomenons of normal aging, and are crazy about
Slow-witted, mild cognitive impairment and normal aging occur from cognitive decline state different degrees of in the elderly, the nervous system disease
Have become the big killer for threatening human health.By taking dementia as an example, senile dementia is also known as Alzheimer disease, has become
The fourth-largest killer of the elderly after cardiovascular disease, malignant tumour, cerebral apoplexy.The disease is a kind of primary degeneration brain
Disease occurs in Senectitude and presenium, and increases with the age and be multiplied, and over 60 years old, illness rate was 4%~8%, 65
It can be more than 30% after increasing to 10%, 80 years old after year.And patient's number of Aged in China dementia is also in significant ascendant trend, according to system
Meter, patient populations occupy first place in the world there are about 6,000,000 at present, and about 1/4 in China in global patient.
Nicergoline is semi-synthetic ergoline derivatives.With alpha-receptor retardation and vasodilative effect.It can reinforce brain
The metabolism of cellular energy increases the utilization of oxygen and glucose.Promote the conversion of neurotransmitter dopamine and increases nerve
Conduction reinforces the synthesis of brain protein, effectively improves memory and learning ability, restore neurogenous normal function and change rapidly
The symptom of kind brain decline, thus the symptom of brain decline can be effectively improved.Clinically Nicergoline is with its unique curative effect,
It is widely used.
Nicergoline is degradable under high temperature and super-humid conditions to wet and thermo-responsive.It is carried out in Nicergoline and auxiliary material
In Study on Compatibility, compatibility is poor under conditions of high humidity with different types of disintegrating agent for discovery Nicergoline, this and disintegration
Agent easily moisture absorption is related.Nicergoline is BCS 2 class drugs of classification, belongs to low-solubility high osmosis drug, Nicergoline is being made
Dissolution in agent is to influence the key factor of bioavilability.The nicergoline tablets listed at present, some stability is preferable, but body
Disintegration is poor in outer medium, and vivo biodistribution availability is low；Some disintegrations are good, but stability is poor, impurity rapid development, imitate the phase
Inside it is difficult to qualification.Needing the technical issues of overcoming is, influencing each other between stability of equilibrium and disintegration, and it is full to obtain the two
The preparation required enough.
It attempts to prepare Buddhist nun ergot using Nicergoline, microcrystalline cellulose, calcium monohydrogen phosphate, carmethose and magnesium stearate
Forest tract.Wherein, it is coated for film-coating or sugar-coat.It is that microcrystalline cellulose and carboxylic first are fine to advantageous auxiliary material is disintegrated in label composition
Plain sodium is tieed up, wherein microcrystalline cellulose is that filler has weaker calving disaggregation, and market model is more；Carmethose is parent
Aqueous binder, on the market according to viscosity difference be divided into it is low it is viscous, in glue and high-adhesive.Using above-mentioned composition, for reality
The purpose of existing fater disintegration dissolution, the scheme normally occurred are the microcrystalline celluloses using different model, improve disintegration；Or
The carmethose of different model is replaced, hydrophily is improved.
It is tested, the microcrystalline cellulose such as granule for the various different models that domestic market is commercially available is respectively adopted
The carmethose of the PH101 of diameter, large-sized PH200, highdensity PH301, the KG802 of low-density and different viscosities
Such as low viscous 7LF PH, in 7MF PH, the high viscous 7HF PH that glue, adopted after mixing auxiliary material and main ingredient using conventional method
The nicergoline tablets being prepared with vertical compression technique, or pass through the techniques such as wet granulation, drying, whole grain, sieving, tabletting, preparation
Obtained nicergoline tablets cannot be disintegrated completely, and dissolution is slow.
Summary of the invention
Based on current nicergoline tablets there are the problem of, will the present invention provides a kind of preparation method of nicergoline tablets
Microcrystalline cellulose and carmethose in prescription are pelletized first, by microcrystalline cellulose-carmethose of preparation
Direct tablet compressing after particle is mixed with Nicergoline, calcium monohydrogen phosphate, magnesium stearate again is coated and aluminum-plastic packaged, obtains Nicergoline
Piece.It can be realized quick and complete disintegration using nicergoline tablets prepared by the method provided by the present invention, achieve the purpose that Fast Stripping.
It is demonstrated experimentally that if not using method provided in the present invention, and use Nicergoline, microcrystalline cellulose, carboxylic
Methylcellulose sodium, calcium monohydrogen phosphate, magnesium stearate powder direct tablet compressing technique or after main ingredient, auxiliary material are mixed jointly through wet process system
The nicergoline tablets of grain technique preparation, can not achieve the purpose of fater disintegration, Fast Stripping.
The present invention provides a kind of nicergoline tablets vertical compression technique without traditional disintegrating agent, using technique provided by the invention
The nicergoline tablets disintegration of preparation rapidly, has good stability.
By in prescription microcrystalline cellulose and carmethose by granulation, make to be disintegrated completely, dissolution is slow
Prescription becomes being disintegrated quickly, completely, dissolves out rapid prescription.Method provided by the invention had both been free of traditional disintegrating agent and had guaranteed
The stability of product, and realize the fater disintegration of nicergoline tablets, dissolution.
A kind of preparation method of fater disintegration type nicergoline tablets, key step in the present invention are as follows:
Step 1
Prepare the composite auxiliary material particle with fast disintegration property, specific preparation process is, by prescription microcrystalline cellulose and
Carmethose is pelletized using wet granulation technology, by the microcrystalline cellulose of preparation-carmethose particle drying,
Size controlling is carried out to the particle after drying, obtains the composite auxiliary material particle with fast disintegration property.
Step 2
Mixing: the microcrystalline cellulose of preparation-carmethose particle, Nicergoline, calcium monohydrogen phosphate, magnesium stearate are mixed one
Determine revolution, obtains total mix powder.
Step 3
Tabletting: the total mix powder of preparation is placed in tablet press machine, carries out tabletting, monitors relevant parameter, and Nicergoline plain piece is made.
Step 4
Coating: the Nicergoline plain piece of preparation is placed in high-efficiency coating pot and carries out film coating, obtains Nicergoline coating tablet.
Step 5
Aluminum-plastic packaged: Nicergoline coating tablet is packed, and finished product is obtained.The packaging refers to aluminum-plastic packaged, material PVC-
Aluminium or PVDC-PVC- aluminium.
A further improvement of the present invention is that:
Microcrystalline cellulose and carmethose weight ratio are 10:1~30:1 in step 1；Microcrystalline cellulose and carboxymethyl cellulose
Sodium wet granulation technology includes wet mixing granulation and boiling granulating technique；Microcrystalline cellulose-carmethose particle
Dry includes oven drying and fluidized drying, and drying temperature is 30~70 DEG C；Microcrystalline cellulose-carmethose particle carries out
Size controlling is to carry out whole grain to microcrystalline cellulose-carmethose particle using 18-200 mesh screen.
Mixing described in step 2 includes two step of premix total mix.The premix is that microcrystalline cellulose-carboxylic first is fine
Plain sodium particle, Nicergoline, calcium monohydrogen phosphate is tieed up to be mixed；Total mix is that magnesium stearate is added in premixing flour to carry out total mix.
Relevant parameter is monitored in step 3 refers to the monitoring in tableting processes to piece thickness, tablet weight variation, hardness.
Film coating in step 4, the coating material of selection are film coating pre-mix dose, including HPMC type and PVA type.
Aluminum-plastic packaged in step 5 is PVDC-PVC- aluminium material.
A further improvement of the present invention is that:
Microcrystalline cellulose and carmethose weight ratio are 15:1~20:1 in step 1；Microcrystalline cellulose and carboxymethyl cellulose
Sodium wet granulation technology selects wet mixing granulation；Microcrystalline cellulose-carmethose particle drying temperature be 40~
60℃；It is using 24-100 mesh screen to microcrystalline cellulose-carboxylic that microcrystalline cellulose-carmethose particle, which carries out size controlling,
Methylcellulose sodium particle carries out whole grain.
A further improvement of the present invention is that:
It is using 40-80 mesh screen to crystallite fibre that microcrystalline cellulose-carmethose particle, which carries out size controlling, in step 1
It ties up element-carmethose particle and carries out whole grain.
Film coating in step 4 is HPMC type film coating pre-mix dose, main to form are as follows: HPMC, titanium dioxide and poly-
Ethylene glycol.
By adopting the above-described technical solution, the technological progress achieved by the present invention is:
(1) the present invention provides a kind of novel method for improving nicergoline tablets disintegration, do not have before making the present invention by crystallite
Cellulose and carmethose are pelletized, to improve any report of disintegration.It is fine using crystallite prepared by the present invention
Element-carmethose particle is tieed up in addition to for nicergoline tablets, it may also be used in other any quickly disintegrated tablets of need.
(2) microcrystalline cellulose-carmethose particle that the present invention is prepared using committed step, it is main in prescription
Effect is the nicergoline tablets fater disintegration for making preparation, additionally has the function of adhesive and filler.It is demonstrated experimentally that if
It does not use method provided in the present invention, and uses Nicergoline, microcrystalline cellulose, carmethose, calcium monohydrogen phosphate, hard
Fatty acid magnesium technique of direct powder compression or the Nicergoline prepared through wet granulation technology after mixing main ingredient, auxiliary material jointly
Piece can not achieve the purpose of fater disintegration, Fast Stripping.
(3) using, without traditional disintegrating agent, the nicergoline tablets of preparation exist in the nicergoline tablets of the technical program preparation
It is not easy to moisture absorption during preparation process and storage, it has good stability.
Detailed description of the invention
The dissolution curve (n=6) of Fig. 1 embodiment and reference examples in pH1.2 medium；
The dissolution curve (n=6) of Fig. 2 embodiment and reference examples in pH4.0 medium；
The dissolution curve (n=6) of Fig. 3 embodiment and reference examples in pH6.8 medium；
The leaching condition used in above-mentioned dissolution curve investigation are as follows: slurry processes, 100 turns, 900ml medium, every sub-sampling 5ml, sampling
The blank dissolution medium of same volume is added afterwards.Detection method: HPLC method, Detection wavelength 288nm.
Specific embodiment
Description is of the invention in the examples below that now, these embodiments are merely illustrative the present invention, without to protection
Range causes to limit.
Raw materials used and auxiliary material is common marketable material and auxiliary material unless otherwise indicated in the following example.Used
Capital equipment is wet mixing pelletizer, producer: Shenzhen Xinyi spy Science and Technology Ltd., model: G10.Rotary tablet machine,
Producer: Shanghai information source pharmaceutical machine Co., Ltd, model: ZPS8.Three-dimensional mixer, producer: it is limited that industry manufacture is closed in Liaocheng ten thousand
Company, model: SBH-10.Small-sized seed-coating machine, producer: Shanghai Huanghai Sea medicine inspection Instrument Ltd., model: BY300A.Tablet is hard
Spend instrument, producer: Tianda Tianfa Technology Co., Ltd., model: YD-20KZ.Intelligent disintegration tester, producer: Tianjin is extremely big
Tian Fa Science and Technology Ltd., model: 2B-2E.Dissolving-out tester, producer: Tianda Tianfa Technology Co., Ltd., model:
RC8MD.High performance liquid chromatograph, producer: Shimadzu Scisakusho Ltd, model: LC-2030C.
Prescription, composition and the preparation process of fater disintegration type nicergoline tablets:
Embodiment 1
Composition (10mg specification) in the preparation of 1 embodiment of table, 1 nicergoline tablets
Note: 1. microcrystalline celluloses, carmethose and purified water throw 5% by recipe quantity is high, to offset pelletization loss；
2. prepare coating solution, polygamy system 10%, to offset coating process loss.
2, preparation process
(1) microcrystalline cellulose and carmethose granulation
Granulation: weighing microcrystalline cellulose and carmethose by the 105% of recipe quantity, be placed in wet mixing pelletizer, if
It sets rotating speed of agitator and shears slurry revolving speed, unlatching wet mixing pelletizer, dry-mixing 2 minutes.After the dry-mixing time reaches, keep
Wet mixing pelletizer is open state, clicks atomization plus water button carries out atomization plus water.Wet process is kept after atomization plus water
Mixer-granulator is open state, continues granulation 2 minutes.After Granulation time reaches the predetermined time, discharging button is clicked, is carried out
Discharging, closes wet mixing pelletizer after discharging.
It is dry: the microcrystalline cellulose of preparation-carmethose particle is shared equally in baking pan, is placed in drying box, if
Setting temperature is 40~60 DEG C, starts timing when temperature reaches, and every 0.5h samples about 1g after dry 3.5h, is surveyed using quick moisture content
Determine instrument, survey moisture content, after reaching requirement, stops drying, close drying box, record drying time.
Whole grain: carrying out whole grain to microcrystalline cellulose-carmethose particle using the sieve of selected mesh number, by sieve with
On particle crushed, make its all by select mesh number sieve.After whole grain, microcrystalline cellulose-carboxylic for will obtaining
Methylcellulose sodium particle is placed in clean material bag, sealing, spare.
(2) it mixes
Premix: microcrystalline cellulose-carmethose particle, Nicergoline and the calcium monohydrogen phosphate for weighing recipe quantity is placed in mixing machine
It is interior.It covers hopper cover and opens mixing machine, carry out premixed operation, mixing revolution is 150~300 turns.
Total mix: it weighs recipe quantity magnesium stearate and is placed in premix mixing machine, cover hopper cover and open mixing machine, carry out total mix
Operation, mixing revolution are 100~200 turns.Total mix particle in mixing machine is discharged to clean material bag, after sampling, sealing,
The sample of taking-up is for measuring total mix powder content.
(3) tabletting
Total mix powder is added at one time in tablet press machine hopper, tablet press machine is opened, tablet press machine revolving speed is set as 20rpm and carries out tabletting
It operates, the clean facilities material bag sack of powder charge is tied on tablet press machine discharge port with silica gel elastic band in tableting processes, avoids medicine
Piece exposure.It is thick that appearance, slice weight and piece are monitored in tableting processes.Inspection is sampled after tabletting.Plain piece will be housed after sampling
Clean facilities material bag sealing, be placed in Aluminum-plastic composite bag, seal, carry out mark storage it is spare.
(4) it is coated
The preparation of coating solution: weighing film coating pre-mix dose and purified water by the 110% of recipe quantity, and coating pre-mixing agent is placed in and is stirred
It mixes in the purified water under state, quickly stirs, so that the agglomerate to be formed is scattered, then reducing mixing speed makes vortex almost disappear, after
Continuous stirring 45 minutes, it is spare.
Coating process: installing seed-coating machine, and adjusting compressed air pressure is 0.05~0.3mpa.Set coating pan revolving speed as
15~25rpm, setting inlet air temperature are 40~70 DEG C, adjust air inlet angle, make piece bed tempertaure at 40~55 DEG C.Plain piece is added
Into coating pan, seed-coating machine is opened, is preheated 10~30 minutes, sampling weighs slice weight before being coated.Wriggling revolution speed is set, makes to wrap
Clothing flow velocity is 5~15g/ minutes, is coated.Coating tablet appearance is checked in coating process.After coating, closes and wriggle
Pump, continues 10~30 minutes dry, sampling, and slice weight after weighing coating calculates coating weight gain.It is sampled after coating, detects water
Part, content and dissolution curve.After coating tablet is cooling, discharge to clean polybag, sealing.
(5) aluminum-plastic packaged
It is aluminum-plastic packaged: to install aluminium-plastic bubble plate packing machine, open compressed air, open cooling-water machine, set each temperature of heating plate 140
± 20 DEG C, 180 ± 20 DEG C of heat-sealing temperature, power on, preheats 20~30 minutes.Tablet is poured into hopper, to each heating plate temperature
After degree reaches setting value, unlatching host, leakage detection apparatus, empty machine are run, and determine that bubble eye is formed, sealed, lot number imprints, punching is normal
Blanking switch life's work is opened afterwards.After normal packaging, periodically carries out quality and check oneself and record.Rejecting at any time in packaging process has
The unqualified tablet such as stain, color spot, loose pieces, sliver rejects abnormal/underproof plastic-aluminum piece.After packaging, packet is taken at random
Sample after dress is detected by internal control quality standard.
The preparation process of following example 2 to embodiment 5 is consistent with the preparation process of embodiment 1, and composition is different.
Embodiment 2
Composition (5mg specification) in the preparation of 2 embodiment of table, 2 nicergoline tablets
Note: 1. microcrystalline celluloses, carmethose and purified water throw 5% by recipe quantity is high, to offset pelletization loss；
2. prepare coating solution, polygamy system 10%, to offset coating process loss.
Embodiment 3
Composition (30mg specification) in the preparation of 3 embodiment of table, 3 nicergoline tablets
Note: 1. microcrystalline celluloses, carmethose and purified water throw 5% by recipe quantity is high, to offset pelletization loss；
2. prepare coating solution, polygamy system 10%, to offset coating process loss.
Embodiment 4
Composition (10mg specification) in the preparation of 4 embodiment of table, 4 nicergoline tablets
Note: 1. microcrystalline celluloses, carmethose and purified water throw 5% by recipe quantity is high, to offset pelletization loss；
2. prepare coating solution, polygamy system 10%, to offset coating process loss.
Embodiment 5
Composition (10mg specification) in the preparation of 5 embodiment of table, 5 nicergoline tablets
Note: 1. microcrystalline celluloses, carmethose and purified water throw 5% by recipe quantity is high, to offset pelletization loss；
2. prepare coating solution, polygamy system 10%, to offset coating process loss.
Reference examples:
Powder vertical compression technique and wet granulation technology preparation reference examples sample is respectively adopted.
Reference examples 1
Composition (10mg specification) in the preparation of 6 reference examples of table, 1 nicergoline tablets
Note: when 1. preparation coating solution, polygamy system 10%, to offset coating process loss.
Preparation process
(1) it mixes
Premix: Nicergoline, microcrystalline cellulose, carmethose and the calcium monohydrogen phosphate for weighing recipe quantity are placed in mixing machine.
It covers hopper cover and opens mixing machine, carry out premixed operation, mixing revolution is 150~300 turns.
Total mix: it weighs recipe quantity magnesium stearate and is placed in premix mixing machine, cover hopper cover and open mixing machine, carry out total mix
Operation, mixing revolution are 100~200 turns.Total mix particle in mixing machine is discharged to clean material bag, after sampling, sealing,
The sample of taking-up is for measuring total mix powder content.
(2) tabletting
Total mix powder is added at one time in tablet press machine hopper, tablet press machine is opened, tablet press machine revolving speed is set as 20rpm and carries out tabletting
It operates, the clean facilities material bag sack of powder charge is tied on tablet press machine discharge port with silica gel elastic band in tableting processes, avoids medicine
Piece exposure.It is thick that appearance, slice weight and piece are monitored in tableting processes.Inspection is sampled after tabletting.Plain piece will be housed after sampling
Clean facilities material bag sealing, be placed in Aluminum-plastic composite bag, seal, carry out mark storage it is spare.
(3) it is coated
The preparation of coating solution: weighing film coating pre-mix dose and purified water by the 110% of recipe quantity, and coating pre-mixing agent is placed in and is stirred
It mixes in the purified water under state, quickly stirs, so that the agglomerate to be formed is scattered, then reducing mixing speed makes vortex almost disappear, after
Continuous stirring 45 minutes, it is spare.
Coating process: installing seed-coating machine, and adjusting compressed air pressure is 0.05~0.3mpa.Set coating pan revolving speed as
15~25rpm, setting inlet air temperature are 40~70 DEG C, adjust air inlet angle, make piece bed tempertaure at 40~55 DEG C.By plain piece plus
Enter into coating pan, open seed-coating machine, preheat 10~30 minutes, sampling weighs slice weight before being coated.Wriggling revolution speed is set, is made
Being coated flow velocity is 5~15g/ minutes, is coated.Coating tablet appearance is checked in coating process.After coating, closes and wriggle
Pump, continues 10~30 minutes dry, sampling, and slice weight after weighing coating calculates coating weight gain.It is sampled after coating, detects water
Part, content and dissolution curve.After coating tablet is cooling, discharge to clean polybag, sealing.
(4) aluminum-plastic packaged
It is aluminum-plastic packaged: to install aluminium-plastic bubble plate packing machine, open compressed air, open cooling-water machine, set each temperature of heating plate 140
± 20 DEG C, 180 ± 20 DEG C of heat-sealing temperature, power on, preheats 20~30 minutes.Tablet is poured into hopper, to each heating plate temperature
After degree reaches setting value, unlatching host, leakage detection apparatus, empty machine are run, and determine that bubble eye is formed, sealed, lot number imprints, punching is normal
Blanking switch life's work is opened afterwards.After normal packaging, periodically carries out quality and check oneself and record.Rejecting at any time in packaging process has
The unqualified tablet such as stain, color spot, loose pieces, sliver rejects abnormal/underproof plastic-aluminum piece.After packaging, packet is taken at random
Sample after dress is detected by internal control quality standard.
Following 2 preparation process of reference examples and reference examples 1 are consistent.
Reference examples 2
Composition (10mg specification) in the preparation of 7 reference examples of table, 2 nicergoline tablets
Note: when 1. preparation coating solution, polygamy system 10%, to offset coating process loss.
Reference examples 3
Composition (10mg specification) in the preparation of 8 reference examples of table, 3 nicergoline tablets
Note: 1. microcrystalline celluloses, carmethose, calcium monohydrogen phosphate and purified water throw 5% by recipe quantity is high, to offset granulation
Process losses；2. prepare coating solution, polygamy system 10%, to offset coating process loss.
Preparation process
(1) auxiliary material wet granulation
Granulation: microcrystalline cellulose, carmethose and calcium monohydrogen phosphate are weighed by the 105% of recipe quantity, is placed in wet-mixing system
Grain machine in, setting rotating speed of agitator and shearing slurry revolving speed, open wet mixing pelletizer, dry-mixing 2 minutes.The dry-mixing time reaches
After arriving, holding wet mixing pelletizer is open state, clicks atomization plus water button carries out atomization plus water.After atomization plus water
Holding wet mixing pelletizer is open state, continues granulation 5 minutes.After Granulation time reaches the predetermined time, discharging is clicked
Button discharges, and wet mixing pelletizer is closed after discharging.
It is dry: the granules of accessories of preparation to be shared equally in baking pan, is placed in drying box, setting temperature is 40~60 DEG C, to
Start timing when temperature reaches, every 0.5h samples about 1g after dry 4.0h, using rapid moisture analyzer, surveys moisture content, reaches and want
After asking, stop drying, close drying box, records drying time.
Whole grain: whole grain is carried out to granules of accessories using the sieve of selected mesh number, particle more than sieve is crushed, is made
Its all passes through the sieve of selected mesh number.After whole grain, obtained granules of accessories is placed in clean material bag, sealing,
It is spare.
(2) mixing, (3) tabletting, (4) coating, (5) aluminum-plastic packaged same embodiment 1.
Reference examples 4
Composition (5mg specification) in the preparation of 9 reference examples of table, 4 nicergoline tablets
Note: when 1. preparation coating solution, polygamy system 10%, to offset coating process loss.
Preparation process
(1) wet granulation
Granulation: Nicergoline, microcrystalline cellulose, carmethose and the calcium monohydrogen phosphate of recipe quantity are weighed, wet-mixing is placed in
In granulator, setting rotating speed of agitator and shearing slurry revolving speed, unlatching wet mixing pelletizer, dry-mixing 2 minutes.The dry-mixing time
After reaching, holding wet mixing pelletizer is open state, clicks atomization plus water button carries out atomization plus water.Atomization plus water terminate
Keeping wet mixing pelletizer afterwards is open state, continues granulation 5 minutes.After Granulation time reaches the predetermined time, point is hit
Expect button, discharges, wet mixing pelletizer is closed after discharging.
It is dry: the granules of accessories of preparation to be shared equally in baking pan, is placed in drying box, setting temperature is 40~60 DEG C, to
Start timing when temperature reaches, every 0.5h samples about 1g after dry 4.0h, using rapid moisture analyzer, surveys moisture content, reaches and want
After asking, stop drying, close drying box, records drying time.
Whole grain: whole grain is carried out to granules of accessories using the sieve of selected mesh number, particle more than sieve is crushed, is made
Its all passes through the sieve of selected mesh number.After whole grain, obtained granules of accessories is placed in clean material bag, sealing,
It is spare.
(2) mixing, (3) tabletting, (4) coating, (5) aluminum-plastic packaged same embodiment 1.
Quality research
The sample prepared using embodiment 1-5 and reference examples 1-4 is detected by the quality standard of formulation, especially compared
The dissolution curve situation of embodiment 1-5 sample and reference examples 1-4 sample in different media.
10 embodiment 1-5 of table and reference examples prepare the testing result of sample
By visible 5 sample of embodiment 1- embodiment prepared using the method provided by the present invention of data in table 10, in pH6.8 medium
Dissolution is apparently higher than the sample of reference examples 1-4 preparation.Disintegration time limited investigates the equal energy of sample for showing prepared by embodiment 1- embodiment 5
Quick and complete disintegration, and reference examples 1 and 2 sample of reference examples are not disintegrated, reference examples 3 and the disintegration of 4 sample of reference examples are incomplete.
Sample prepared by embodiment 1 to embodiment 5 is disintegrated rapidly within 1min in above-mentioned 3 kinds of media, is shown as
Fast Stripping.Reference examples 1 and 2 sample of reference examples in pH1.2 medium and pH4.0 medium, because in prescription calcium monohydrogen phosphate in pH1.2
It gradually dissolves, the slow corrosion of sample, but is not disintegrated in medium and pH4.0 medium, it is partially slow to show dissolution；In pH6.8 medium
Because calcium monohydrogen phosphate is insoluble, reference examples sample is not disintegrated, and can not be dissolved out.Reference examples 3 and as usual 4 samples in above-mentioned 3 kinds of media,
Disintegration is slowly and incomplete, is disintegrated at not continuing to be disintegrated after big, shows as slowly dissolving out, in the same time the amount of dissolution
It is significantly less than embodiment.
Claims (7)
1. a kind of preparation method of fater disintegration type nicergoline tablets, it is characterised in that include the following steps:
A. wet granulation technology preparation has the composite auxiliary material particle of fast disintegration property, will not have fater disintegration in prescription
Two kinds of auxiliary materials of ability are pelletized, and are made it have the specific preparation process of quickly disintegrated ability and are, the crystallite in prescription is fine
Dimension element and carmethose are pelletized using wet granulation technology, by microcrystalline cellulose-carmethose of preparation
Grain is dry, carries out size controlling to the particle after drying, obtains the composite auxiliary material particle with fast disintegration property;
B. composite auxiliary material particle is mixed with main ingredient and other auxiliary materials, tabletting.
2. preparation method as described in claim 1, wherein microcrystalline cellulose and carmethose weight ratio are 10:1~30:
1, preferably 15:1~20:1.
3. the preparation method as described in one of claim 1-2, wherein microcrystalline cellulose and carmethose wet granulation work
Skill includes wet mixing granulation and boiling granulating technique.
4. the preparation method as described in one of claim 1-3, wherein microcrystalline cellulose-carmethose particle drying includes
Oven drying and fluidized drying, drying temperature are 30~70 DEG C, preferably 40~60 DEG C.
5. the preparation method as described in one of claim 1-4, wherein carrying out grain to microcrystalline cellulose-carmethose particle
Diameter control is to carry out whole grain, preferably 24-100 mesh to microcrystalline cellulose-carmethose particle using 18-200 mesh screen
Net, more preferable 40-80 mesh screen.
6. wherein tabletting uses powder vertical compression technique, composition using the preparation method as described in one of claim 1-5
Are as follows: microcrystalline cellulose-carmethose composite particles, Nicergoline, calcium monohydrogen phosphate and magnesium stearate.
7. a kind of preparation method of fater disintegration type nicergoline tablets, includes the following steps:
(1) wet granulation technology preparation has the composite auxiliary material particle of fast disintegration property, will not have fater disintegration in prescription
Two kinds of auxiliary materials of ability are pelletized, and quickly disintegrated ability is made it have, and specific preparation process is, the crystallite in prescription is fine
Dimension element and carmethose are pelletized using wet granulation technology, by microcrystalline cellulose-carmethose of preparation
Grain is dry, carries out size controlling to the particle after drying, obtains the composite auxiliary material particle with fast disintegration property;
(2) mix: by the microcrystalline cellulose of preparation-carmethose particle, Nicergoline, calcium monohydrogen phosphate, magnesium stearate into
Row mixing obtains total mix powder, and the mixing includes two step of premix total mix, and the premix is by microcrystalline cellulose-carboxylic first
Sodium cellulosate particle, Nicergoline, calcium monohydrogen phosphate are mixed；Total mix is that magnesium stearate is added in premixing flour to carry out total mix;
(3) tabletting: the total mix powder prepared in (2) is placed in tablet press machine, carries out tabletting, and Nicergoline plain piece is made;
(4) it is coated: the Nicergoline plain piece of preparation being placed in high-efficiency coating pot and carries out film coating, obtain Nicergoline coating
Piece, the film coating, the coating material of selection are film coating pre-mix dose, including HPMC type and PVA type, preferably HPMC
Type;
(5) aluminum-plastic packaged: Nicergoline coating tablet is packed, and obtains finished product, and described is packaged as aluminium-plastic bubble plate packing, material
Matter is PVC- aluminium or PVDC-PVC- aluminium, preferably PVDC-PVC- aluminium material.
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| CN115068435A (en) * | 2022-08-03 | 2022-09-20 | 昆山龙灯瑞迪制药有限公司 | Preparation method of nicergoline tablets |
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Denomination of invention: A rapidly disintegrating nieergolin tablet and its preparation method Effective date of registration: 20230508 Granted publication date: 20210831 Pledgee: Bank of China Limited Xianning branch Pledgor: Hubei kelaiwei biopharmaceutical Co.,Ltd. Registration number: Y2023420000190 |