CN107773553A - A kind of memantine sustained release pellet and preparation method thereof - Google Patents
A kind of memantine sustained release pellet and preparation method thereof Download PDFInfo
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- CN107773553A CN107773553A CN201610735626.6A CN201610735626A CN107773553A CN 107773553 A CN107773553 A CN 107773553A CN 201610735626 A CN201610735626 A CN 201610735626A CN 107773553 A CN107773553 A CN 107773553A
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- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
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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
- A61K31/13—Amines
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- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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Abstract
The present invention relates to a kind of memantine sustained release pellet and preparation method thereof, the memantine sustained release pellet includes blank capsule core, the medicated layer comprising memantine and sustained-release coating layer successively from the inside to the outside, it is characterised in that：Described sustained-release coating layer includes first layer ethylcellulose coat layer and second layer Surelease coatings.Sustained release pellet outward appearance rounding of the present invention, uniform particle diameter, good fluidity；Without phenomenon of burst release and release the drug completely, stability is good.
Description
Technical field
The present invention relates to a kind of Memantine sustained release pellet and its preparation method, belong to pharmaceutical technology field.
Background technology
Alzheimer's disease (Alzheimer ' s Disease, AD) is a kind of central nervous system degenerative disease, is old
A term dull-witted most common type, is the irreversible carry out sexual disorder that a kind of brain cell (neuron) deteriorates, insidious onset,
The course of disease is in chronic progressive, and the incidence of disease increases and increased with the age.Clinical manifestation declines for cognitive ability, mental act is abnormal,
Activity of daily living reduction etc..Research finds that AD pathogenesis is damaged with central cholinergic system and toxicity of excitatory amino acid is relevant.
Data are announced in April, 2012 show that there is nearly 35,600,000 AD patient in the whole world, it is contemplated that number to the year two thousand thirty is doubled according to WHO
(65,700,000), present three times are up to the year two thousand fifty.China AD patient has 6,000,000 or so, it is contemplated that will have to China in 2025
10000000 AD patients.
Memantine is approved for treatment of the moderate to severe AD in Europe at present, and is used for moderate to weight in the U.S.
Spend AD treatment.Memantine is a kind of uncompetitive nmda receptor antagonist with medium compatibility, and it both can be in pathology
In the case of block calcium channel, while reduce the excititoxic effect of Glutamatergic, form normal study and note
Recall, the neuron under pathology virulent state can also be protected.This magnesium ion for being different from physiological blocks and high-affinity NMDA
The complete blocking effect of receptor antagonist.The clinical test of the scholars such as Cummings and 6 Memantine clinical researches are assembled point
Analysis, the Behavioral and psychological symptom for Memantine being treated to AD patient are studied.As a result show, Memantine can effectively alleviate AD trouble
A variety of Behavioral and psychological symptoms of person, two results of study prompt Memantine to intense, aggressive and irritability mental act
Symptom also has significant curative effect.Therefore, severe AD patients in being treated using Memantine, it can obtain significantly and have facing for statistical significance
Bed curative effect, the progress of disease is delayed, while Memantine has good tolerance, prompts using severe AD in Memantine treatment
Patient is very effective treatment method.
CN103181914 protects a kind of Memantine hydrochloride sustained-release capsule, and it is hydrochloric acid mainly to protect capsule inner stuffing
Memantine sustained release pellet, sustained release pellet are made up of the drug containing piller of hydrochloric Memantine with one layer of sustained release coating.Although this patent
Solves the prominent risk released of sustained release tablets, but in the prolonged storage of the capsule, moisture-sensitive wet environment influences.Because hydrochloric acid is beautiful
Buddha's warrior attendant is highly soluble in water, the risk that medicated layer migrates toward slow release layer be present, so as to there is the prominent risk released.Patent CN103417491
Memantine pellet preparations are protected, blank capsule core is mainly protected and is wrapped in the memantine medicine composite bed of outer layer
Technique, but the patent and patent CN103181914 are equally existed and prominent are released risk.Therefore, stable preparation process, invention make salt
The formulation and technology that phenomenon of burst release does not occur under the conditions of hot and humid for sour Memantine is the technical problem for being badly in need of solving.
The content of the invention
Multiple coatings are carried out using more particle dosage unit membrane control technologies, each unit it is an object of the present invention to design,
Memantine sustained release pellet is prepared, wherein sustained-release coating layer is controlled using double-layer sustained release film, both ensure that product stability was good,
Also ensure that sustained drug, uniformly slowly and fully discharge.
To solve the above problems, technical scheme provided by the invention is as follows：A kind of memantine sustained release pellet, the salt
Sour Memantine sustained release pellet includes blank capsule core, the medicated layer comprising memantine and sustained-release coating layer successively from the inside to the outside,
It is characterized in that：Described sustained-release coating layer includes first layer ethylcellulose coat layer and second layer Surelease coatings,
Wherein, ethylcellulose coat layer accounts for the 1%-10% of blank capsule core and medicated layer quality, preferably 2%-8%, more preferably 3%-
5%；Surelease coatings account for the 1%-10% of blank capsule core and medicated layer quality, preferably 2%-8%, more preferably 5%-
7%.
Further, memantine sustained release pellet provided by the invention, its blank capsule core, medicated layer, slow release layer are each
Moiety weight percentage is respectively blank capsule core 20%-80%, preferably 45%-75%, more preferably 55%-75%, further
It is preferred that 60%-75%；Medicated layer 10%-50%, preferably 15%-35%, more preferably 18%-30%；Slow release layer 5%-30%, it is excellent
Select 5%-20%, more preferably 8%-15%.
More specifically, first layer ethylcellulose coat layer is in addition to ethyl cellulose, also comprising plasticizer.Described plasticising
One or more of the agent in polyethylene glycol, triethyl citrate, triglyceride and oleic acid.
First layer ethylcellulose coat layer or second layer Surelease coatings also include pore-foaming agent.Described pore
One or more of the agent in HPMC, hydroxypropyl cellulose, polyvinylpyrrolidone or polyethylene glycol.
Ethyl cellulose, pore-foaming agent, the mass ratio of plasticizer are 5~35 in first layer ethylcellulose coat layer：1~
10：1, it is excellent
Select 5~35：1~6：1；Surelease aqueous dispersions, the quality of pore-foaming agent in second layer Surelease coatings
Than for 10~40：
0~1, preferably 5~40：0~1.
More specifically, its shaping of described memantine sustained release pellet blank capsule core used is selected from microcrystalline cellulose ball
One or more in core, sucrose capsule core, starch capsule core.The particle size range of described blank capsule core is 20-60 mesh.
More specifically, the medicated layer of described memantine sustained release pellet is also wrapped in addition to active ingredient memantine
Include adhesive, antiplastering aid.
Wherein, the one kind or more of adhesive in HPMC, hydroxypropyl cellulose, polyvinylpyrrolidone
Kind；One or more of the antiplastering aid in talcum powder, silica.
Blank capsule core, memantine, adhesive, the mass ratio of antiplastering aid are 1~30 in described medicated layer：1~10：
0~2：0~1, preferably 10~30：2~10：0~2：0~1.
The invention further relates to a kind of preparation method of described memantine sustained release pellet, it includes：
(1) memantine, adhesive, antiplastering aid are added in ethanol water, are made containing decoction；
(2) using blank capsule core as core, medicine liquid spray will be contained and be wrapped in blank capsule core, drug containing piller is made；
(3) ethyl cellulose, plasticizer, pore-foaming agent are added in ethanol water, sustained release coating liquid 1 is made；By water, cause
Hole agent is added in Surelease aqueous dispersions, and sustained release coating liquid 2 is made；
(4) using drug containing piller as core, sustained release coating liquid 1, sustained release coating liquid 2 is sprayed successively and are wrapped in medicated layer piller
On, slow release layer piller is made, aging, produces.
Wherein described ethanol solution concentration is 10%-95%, preferably 40%-95%.
Described spray pattern is the spray spraying medicine-feeding of fluid bed bottom, and described aging techniques are to make micropill in fluid bed
40-60 DEG C of online dry 0.5-2 hour.
Compared with prior art, the present invention is using ethylcellulose coat layer and Surelease aqueous dispersion coatings
Double-layer sustained release coatings design, and internal layer ethylcellulose coat layer can effectively prevent the medicated layer outer layers under the conditions of hot and humid
Slow release layer migration releases problem so as to produce to dash forward, it is ensured that the stability of micropill；The Surelease coatings of outer layer can guarantee that simultaneously
Medicine is slowly, lasting, completely release, 12h releases reach more than 90%.
Embodiment
With reference to embodiment, the invention will be further described.
Embodiment 1：The preparation of Memantine sustained release pellet
It is prepared by drug containing piller：Using the ethanol waters of 1600g 50% as medicine-feeding decentralized medium, 70g polyvinyl pyrroles are added
Alkanone, then 280g memantines and 50g talcum powder are dispersed in polyvinylpyrrolidonesolution solution, obtain suspension；Using
Mode is sprayed at fluid bed bottom, and medicine-feeding suspension spraying is added medicine to onto blank capsule core at a temperature of 30-40 DEG C, it is small to obtain drug containing
Ball.
It is prepared by slow-release pill：Using the ethanol waters of 1260g 95% as slow release layer decentralized medium, 2g oleic acid, 2g glycerine are added
Three acid esters, add 20g polyethylene glycol, and stirring adds 116g ethyl celluloses after dissolving, obtains slow release layer suspension；Adopt
Mode is sprayed with fluid bed bottom, slow release layer suspension is sprayed on drug containing piller at a temperature of 30-40 DEG C, it is small to obtain slow release layer
Ball；Make micropill 40-60 DEG C of online dry 0.5-2 hour in fluid bed；Content, filling micropill are determined into corresponding capsule, i.e.,
.
Embodiment 2：The preparation of Memantine slow release layer micropill
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：373g water is added in 560g Surelease aqueous dispersions, stirring obtains slow release layer and mixed
Suspension；Mode is sprayed using fluid bed bottom, the slow release layer suspension made is sprayed to drug containing piller at a temperature of 40-50 DEG C
On, obtain slow release layer piller；Make micropill 40-60 DEG C of online dry 0.5-2 hour in fluid bed；Determine content, filling micropill
Into corresponding capsule, produce.
Embodiment 3：The preparation of Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：Using the ethanol waters of 630g 95% as slow release layer decentralized medium, 1g oleic acid, 1g glycerine three are added
Acid esters, adds 10g polyethylene glycol, and stirring adds 58g ethyl celluloses after dissolving, obtains slow release layer suspension.Using
Mode is sprayed at fluid bed bottom, and the slow release layer suspension made is sprayed on drug containing piller at a temperature of 30-40 DEG C, is sustained
Layer piller 1；
Slow release layer piller 2：187g water is added in 280g Surelease aqueous dispersions, stirring obtains slow release layer suspension
Liquid；Mode is sprayed using fluid bed bottom, the slow release layer suspension made is sprayed to slow release layer piller 1 at a temperature of 40-50 DEG C
On, obtain slow release layer piller 2.
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 4：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3；
Slow release layer piller 2：Using 397g water as slow release layer decentralized medium, 3g triethyl citrates are added, add 60g
Eudragit RL-30D, stirring add 7g talcum powder after dissolving, obtain slow release layer suspension.Using fluid bed bottom spray side
Formula, the slow release layer suspension made is sprayed on drug containing piller at a temperature of 30-40 DEG C, obtains slow release layer piller 2；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 5：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3；
Slow release layer piller 2：Using 209g purified waters as slow release layer decentralized medium, add 7.5g polyethylene glycol and stir, will
Aqueous Solutions of Polyethylene Glycol is added in 250g Surelease aqueous dispersions, and stirring obtains slow release layer suspension；Using fluid bed
Mode is sprayed at bottom, and the slow release layer suspension made is sprayed on slow release layer piller 1 at a temperature of 40-50 DEG C, obtains slow release layer
Piller 2；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 6：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3；
Slow release layer piller 2：It is 293g only by purified water quantitative change with the preparation of slow release layer piller 2 in embodiment 5,
Surelease and polyethylene glycol dosage are as shown above；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 7：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3；
Slow release layer piller 2：It is 418g only by purified water quantitative change with the preparation of slow release layer piller 2 in embodiment 5,
Surelease and polyethylene glycol dosage are as shown above；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 8：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3, only 95% ethanol water dosage is changed into
378g, ethyl cellulose, polyethylene glycol, oleic acid, triglyceride dosage are as shown above；
Slow release layer piller 2：With the preparation of slow release layer piller 2 in embodiment 6；
Small 2 ball of slow release layer is placed in the dry 1-6h of 40-60 DEG C of electric heating constant-temperature blowing drying box；Determine content, filling micropill
Into corresponding capsule, produce.
Embodiment 9：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller in embodiment 1；
Slow release layer piller 2：With the preparation of slow release layer piller 2 in embodiment 6；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 10：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3, oleic acid and triglyceride are only replaced with into lemon
Lemon triethylenetetraminehexaacetic acid ester；
Slow release layer piller 2：With the preparation of slow release layer piller 2 in embodiment 6；
Small 2 ball of slow release layer is placed in the dry 1-6h of 40-60 DEG C of electric heating constant-temperature blowing drying box；Determine content, filling micropill
Into corresponding capsule, produce.
Embodiment 11：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 10, triethyl citrate dosage is adjusted as above
Shown in table；
Slow release layer piller 2：With the preparation of slow release layer piller 2 in embodiment 6；
Small 2 ball of slow release layer is placed in the dry 1-6h of 40-60 DEG C of electric heating constant-temperature blowing drying box；Determine content, filling micropill
Into corresponding capsule, produce.
Embodiment 12：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3,95% ethanol consumption is changed into 711g, ethyl
Cellulose, polyethylene glycol, oleic acid, triglyceride dosage are as shown above；
Slow release layer piller 2：It is 335g, Surelease by purified water quantitative change with the preparation of slow release layer piller 2 in embodiment 6
With polyethylene glycol dosage as shown above；
Small 2 ball of slow release layer is placed in the dry 1-6h of 40-60 DEG C of electric heating constant-temperature blowing drying box；Determine content, filling micropill
Into corresponding capsule, produce.
Embodiment 13：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3；
Slow release layer piller 2：With the preparation of slow release layer piller 2 in embodiment 6；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 14：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3；
Slow release layer piller 2：With the preparation of slow release layer piller 2 in embodiment 6；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 15：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1, polyvinylpyrrolidone is replaced with into hydroxy propyl cellulose
Element.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3；
Slow release layer piller 2：With the preparation of slow release layer piller 2 in embodiment 6；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Embodiment 16：Prepare Memantine sustained release pellet
It is prepared by drug containing piller：Prepared with drug containing piller in embodiment 1.
It is prepared by slow-release pill：
Slow release layer piller 1：With the preparation of slow release layer piller 1 in embodiment 3；
Slow release layer piller 2：With the preparation of slow release layer piller 2 in embodiment 6；
Make the 40-60 DEG C of online dry 0.5-2 hour in fluid bed of slow release layer piller 2；It is paired to determine content, filling micropill
The capsule answered, is produced.
Capsule in above example is put under 60 DEG C of hot conditions, sampled within 0 day, 10 days, 30 days, using basket method, 100
Under rev/min, in 900ml, 37 DEG C of pH1.2 cushioning liquid, dissolution rate detection is carried out to spansule.
The memantine accumulative releasing degree (n=6) of each micropill in the embodiment of table 1
Example 1-3 results show that the micropill of ethyl cellulose slow release coating fully can not discharge completely after 8h；
The micropill releasing result of Surelease sustained release coatings can meet the release request of slow releasing pharmaceutical, but occur within 10 days in high temperature
Phenomenon of burst release；The micropill dissolution result that ethyl cellulose is combined progress sustained release coating with Surelease is slower, but meets sustained release
The release request of medicine, it is also relatively stable under the high temperature conditions；Example 3-4 results show that Eudragit RL-30D Controlled releases are imitated
Fruit is poor compared with Surelease；Example 5-7 results are shown, pore-foaming agent is added in outer layer Surelease sustained release coatings and forms duct,
The medicine of coating inner side is discharged by these ducts, accelerates drug release rate；And Surelease sustained-release coating layers weightening control
7% or so the release made in blank capsule core and medicated layer quality is preferable, excessive or very few can not reach preferable releasing result；It is real
The result of example 6,8,9 shows that ethylcellulose coat weightening is preferable in 5% or so release of blank capsule core and medicated layer quality, mistake
It is more or very few can not reach preferable releasing result；Example 10-11 shows that the change of plasticizer type or dosage is to final release
As a result influence smaller；Example 12 shows that the drugloading rate for reducing micropill is smaller on the influence of final releasing result；Example 13-14 results
It has been shown that, the release of sucrose capsule core are slightly faster than starch capsule core and microcrystalline cellulose capsule core；The result of example 15 shows that adhesive changes to most
Whole releasing result influences smaller；The result of example 16 is shown, appropriate to adjust adhesive with anti-stick agent level to final releasing result shadow
Sound is smaller.
Claims (15)
1. a kind of memantine sustained release pellet, the memantine sustained release pellet include successively from the inside to the outside blank capsule core,
Medicated layer and sustained-release coating layer comprising memantine, it is characterised in that：Described sustained-release coating layer includes first layer ethyl
Coated cellulose layer and second layer Surelease coatings, wherein, ethylcellulose coat layer accounts for blank capsule core and medicated layer matter
The 1%-10% of amount, preferably 2%-8%, more preferably 3%-5%；Surelease coatings account for blank capsule core and medicated layer quality
1%-10%, more preferably preferably 2%-8%, 5%-7%.
2. memantine sustained release pellet according to claim 1, it is characterised in that blank capsule core, medicated layer, slow release layer
Each several part percentage by weight is respectively blank capsule core 20%-80%, preferably 45%-75%, more preferably 55%-75%, more to enter one
Walk preferred 60%-75%；Medicated layer 10%-50%, preferably 15%-35%, more preferably 18%-30%；Slow release layer 5%-30%,
It is preferred that 5%-20%, more preferably 8%-15%.
3. memantine sustained release pellet according to claim 1, it is characterised in that first layer ethylcellulose coat layer
In addition to ethyl cellulose, also comprising plasticizer.
4. memantine sustained release pellet according to claim 3, it is characterised in that described plasticizer is selected from poly- second two
One or more in alcohol, triethyl citrate, triglyceride and oleic acid.
5. memantine sustained release pellet according to claim 1, it is characterised in that first layer ethylcellulose coat layer
Or second layer Surelease coatings also include pore-foaming agent.
6. memantine sustained release pellet according to claim 5, it is characterised in that described pore-foaming agent is selected from hydroxypropyl first
One or more in base cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone or polyethylene glycol.
7. according to the memantine sustained release pellet described in claim any one of 2-6, it is characterised in that first layer ethyl cellulose
Ethyl cellulose, pore-foaming agent, the mass ratio of plasticizer are 5~35 in plain coatings：1~10：1, preferably 5~35：1~6：1；The
Surelease aqueous dispersions, the mass ratio of pore-foaming agent are 10~40 in two layers of Surelease coatings：0~1, preferably 5~40：
0~1.
8. memantine sustained release pellet according to claim 1, it is characterised in that it is molded blank capsule core choosing used
One or more from microcrystalline cellulose capsule core, sucrose capsule core, starch capsule core.
9. memantine sustained release pellet according to claim 8, it is characterised in that the particle diameter model of described blank capsule core
Enclose for 20-60 mesh.
10. memantine sustained release pellet according to claim 1, it is characterised in that described medicated layer removes active ingredient
Outside memantine, in addition to adhesive, antiplastering aid.
11. memantine sustained release pellet according to claim 10, it is characterised in that it is fine that adhesive is selected from hydroxypropyl
Tie up the one or more in element, hydroxypropyl cellulose, polyvinylpyrrolidone；Antiplastering aid is in talcum powder, silica
It is one or more.
12. according to the memantine sustained release pellet described in any one of claim 10 or 11, it is characterised in that described drug containing
Blank capsule core, memantine, adhesive, the mass ratio of antiplastering aid are 1~30 in layer：1~10：0~2：0~1, preferably 10~
30：2~10：0~2：0~1.
13. the preparation method of the memantine sustained release pellet described in claim 1, it includes：
(1) memantine, adhesive, antiplastering aid are added in ethanol water, are made containing decoction；
(2) using blank capsule core as core, medicine liquid spray will be contained and be wrapped in blank capsule core, drug containing piller is made；
(3) ethyl cellulose, plasticizer, pore-foaming agent are added in ethanol water, sustained release coating liquid 1 is made；By water, pore-foaming agent
Add in Surelease aqueous dispersions, sustained release coating liquid 2 is made；
(4) using drug containing piller as core, sustained release coating liquid 1, sustained release coating liquid 2 is sprayed successively and are wrapped on medicated layer piller,
Slow release layer piller is made, aging, produces.
14. preparation method according to claim 13, wherein described ethanol solution concentration is 10%-95%, preferably
40%-95%.
15. preparation method according to claim 13, wherein described spray pattern is the spray spraying medicine-feeding of fluid bed bottom, institute
The aging techniques stated are to make micropill 40-60 DEG C of online dry 0.5-2 hour in fluid bed.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114748443A (en) * | 2022-04-20 | 2022-07-15 | 北京丰科睿泰医药科技有限公司 | Memantine hydrochloride sustained-release pellet and preparation method thereof |
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- 2016-08-26 CN CN201610735626.6A patent/CN107773553A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104013592A (en) * | 2014-06-10 | 2014-09-03 | 浙江京新药业股份有限公司 | Memantine hydrochloride slow-release pill and preparation method thereof |
| CN105816441A (en) * | 2016-05-31 | 2016-08-03 | 北京康立生医药技术开发有限公司 | Memantine hydrochloride and donepezil hydrochloride composite preparation |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114748443A (en) * | 2022-04-20 | 2022-07-15 | 北京丰科睿泰医药科技有限公司 | Memantine hydrochloride sustained-release pellet and preparation method thereof |
| CN114748443B (en) * | 2022-04-20 | 2023-05-02 | 北京丰科睿泰医药科技有限公司 | Memantine hydrochloride sustained-release pellets and preparation method thereof |
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