CN104013592B - Memantine sustained release pill and preparation method thereof - Google Patents
Memantine sustained release pill and preparation method thereof Download PDFInfo
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- CN104013592B CN104013592B CN201410254808.2A CN201410254808A CN104013592B CN 104013592 B CN104013592 B CN 104013592B CN 201410254808 A CN201410254808 A CN 201410254808A CN 104013592 B CN104013592 B CN 104013592B
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Abstract
The invention discloses a kind of memantine to be sustained pill.The capsule inner stuffing is memantine slow-release pill, and the memantine slow-release pill includes blank capsule core, the main medicament layer of hydrochloric Memantine, isolation coat layer and sustained-release coating layer successively from the inside to the outside.Stability of the present invention is good, without phenomenon of burst release, it is ensured that sustained drug, uniformly slowly discharges medicine, the effect of improving product.
Description
Technical field
The present invention relates to a kind of memantine sustained release pill and preparation method thereof, belong to pharmaceutical technology field.
Background technology
With the continuous growth of world population ages and the increasingly raising of living standards of the people, the average life span is also with prolonging
Long, 2002, the whole world the elderly of more than 60 years old accounted for the 20% of world population sum, estimated to the year two thousand fifty, the elderly's quantity
It is up to the 21% of total world population.With world population ages, senile dementia has turned into the matter of utmost importance of human health, hair
Sick rate is as the progress of aging population is in the trend risen year by year.Whole world number of patients is more than 18,000,000 at present, China
Number of patients there are about 6,000,000, be the country that number of patients is most in the world.During memantine (Memantine HCl) is used for
Spend to the treatment of the alzheimer dementia of severe.Alzheimer's disease (AD) is that a kind of brain cell (neuron) deteriorates not
Reversible carry out sexual disorder, it causes the forfeiture of cognitive function, main memory, judgement and reasoning, sports coordination and figure identification.
Late period the disease, all memories and intellectual function may all be lost.People with Alzheimer's disease is in memory, judgement
Problem be present with terms of thinking, so that it is difficult to work or participates in daily life.It and senile dementia, i.e., it is relevant with old-age group
Intellectual deterioration (intelligence lose) it is relevant.Senile dementia is defined as two kinds of main Types：Caused by the atrophy of broad sense
Alzheimer type and as caused by vascular problem, mainly apoplexy etc..In people more than 80 years old, 20% suffers from A Erci
The silent disease in sea.In spite of the medicine that can improve symptom, but Alzheimer's disease can not be cured at present.Memantine is at present in European quilt
Ratify the treatment to severe AD for middle severe, and be used for treatment of the moderate to severe AD in the U.S..In addition, with receiving peace
The AD patient for consoling agent compares, and when giving Memantine to severe AD patients in the treatment to receiving medicine donepezil, generates
Bigger alleviation unexpected to AD symptoms.The result do not showing slightly into moderate AD patients, including giving
The therapeutic alliance of Memantine and other medicinal compounds for being approved for AD treatments does not have compared with the control compound used
Produce any advantage.WO2005/06790B describes one kind and treats the slight method for arriving severe Alzheimer's disease (AD), including
The Memantine or its pharmaceutically acceptable salt of effective dose are given to the subject of needs.This method is directed to by not receiving to control
The subject (naive subject) for the treatment of, and previously once received other medicinal compounds for being approved for AD treatments
Treatment but start Memantine administration before stop AChEI (acetylcholinesterase inhibitor) treatment it is tested earlier than one day
The group of person's composition.WO2006/009769 describes a kind of formulation, and about 4 hours to about 24 hours interior energies maintain Memantine upon administration
The pharmaceutically useful polymer base carrier of rate of release.However, the polymer substrate formation mechenism dependent on numerous state-variables
It is well-known in the art that drug release characteristics, which can be directly affected,.This is particularly difficult in Memantine composition, because U.S. dollar
Firm medicine is dissolved in water and has high osmosis, so any change during matrix is formed all is likely to result in insoluble drug release and suction
Change in receipts.
CN101677960 describe a kind of Memantine extension release pharmaceutical composition, using lipid matter or with it is non-
Material of the lipid matter together as Drug controlled release.Lipid matter is made as matrix Drug controlled release, non-fat metallic substance
To be coated Drug controlled release.However, lipid matter can play extension, the release of water soluble drug memantine is prevented,
But to easily being influenceed in the control of drug releasing rate by more multifactor, such as easily by pharmaceutical composition volume size, surface area with
And the influence of food.Release such as is adjusted plus coating double factor with lipid matter, two variable factors are to a certain extent
It is more difficult to Drug controlled release and reaches preferable release profiles.It is well known that lipid matter compressibility is poor, if used in formula
Measure it is larger, to final composition it is compressing for and problem.If using releasing piece at once, using twice daily
Memantine dosage regimen, this is probably not welcome by patient, because the compliance of patient is as the frequency of medication increases and drops
It is low.Moreover, because faster absorption rate, the adverse events of bigger frequency may be caused by giving releasing piece at once.Therefore, for
The problem of sustained release preparation once a day of pharmaceutically acceptable salt containing Memantine or Memantine is concern.Patent
CN1968684 protects a kind of tune release formulation comprising Memantine, mainly protects and a kind of uses HPMC as skeleton slow-release material
The sustained release tablet for oral use of Memantine.Although sustained release tablets can have the function that steady blood concentration, there is also prominent for sustained release tablets
Risk is released, there is certain potential safety hazard.
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
Solve the prominent risk released of sustained release tablets, but the capsule is vulnerable to the influence of wet environment during long-term storage, due to
Memantine is the material for being highly soluble in water, the risk that medicated layer migrates toward slow release layer be present, so as to equally there is the prominent wind released
Danger.
Patent CN103417491 protects Memantine hydrochloride slow-release pellet preparation, mainly protects blank capsule core and parcel
In the technique of the memantine medicament slow release composite bed of outer layer, but the technique equally existed with patent CN103181914 it is prominent
Release risk.
The content of the invention
It is an object of the present invention to provide a kind of memantine sustained release pill and preparation method thereof.Stability of the present invention
Well, without phenomenon of burst release, it is ensured that sustained drug, uniformly slowly discharge medicine, improve the effect of producing mouth.
In order to solve the above technical problems, technical scheme provided by the invention is as follows：A kind of memantine is sustained pill, salt
Sour Memantine sustained release pill includes the drug containing piller comprising memantine, isolation coat layer and sustained release coating successively from the inside to the outside
Layer.
In above-mentioned memantine sustained release pill, described isolation coat layer includes isolation coat material by weight
70-95 parts, talcum powder 5-30 parts；Described isolation coat material is pyrrolidones, hydroxypropyl cellulose, hydroxypropyl methylcellulose
Element, hydroxyethyl cellulose, ethyl cellulose, IR, Eudragit RL100, Eudragit
RS100, EudragitRL 30D, Eudragit RS 30D, Eudragit NE30D, Aquacoat ECD, Surelease or
Kollicoat RS30D。
In foregoing memantine sustained release pill, described isolation coat material is HPMC.
In foregoing memantine sustained release pill, the quality of described separation layer is the 3%- of drug containing piller quality
20%.
In foregoing memantine sustained release pill, described drug containing piller includes blank capsule core, in the outer of blank capsule core
Face is provided with the main medicament layer of hydrochloric Memantine.
In foregoing memantine sustained release pill, described main medicament layer include by weight memantine 20-50 parts,
Adhesive 7-15 parts, diluent 30-50 parts and antiplastering aid 5-15 parts；Described sustained-release coating layer includes sustained release coating by weight
Material 70-85 parts, polyethylene glycol 10-30 parts and triethyl citrate 0-5 parts；Described Sustained release coating materials ethyl cellulose,
Cellulose acetate, Eudragit RL100, Eudragit RS100, Eudragit RL 30D, Eudragit RS 30D,
It is one or more kinds of in Eudragit NE30D, Aquacoat ECD, Surelease or Kollicoat RS30D.
In foregoing memantine sustained release pill, described adhesive is pyrrolidones, hydroxypropyl cellulose, hydroxypropyl first
Base cellulose, hydroxyethyl cellulose or ethyl cellulose；Described diluent is mannitol, polyethylene glycol, sucrose, lactose or wine
Stone acid；Described antiplastering aid is talcum powder, magnesium stearate, stearic acid or glycerin monostearate；Described solvent be ethanol,
Water, acetone, methanol, the one or more of isopropanol combine.
In foregoing memantine sustained release pill, described adhesive is HPMC；Described diluent
For mannitol；Described antiplastering aid is talcum powder.
The preparation method of foregoing memantine sustained release pill, it is characterised in that：Comprise the following steps；
(1) take hydroxypropyl methylcellulose to be dissolved in solvent and be configured to solution A；Polyethylene glycol and memantine are dissolved in into solvent to match somebody with somebody
Solution B is made；Solution A is added in solution B, talcum powder stirring is added, obtains drug containing coating solution；
(2) drug containing coating solution is coated to blank capsule core, the main medicament layer piller of hydrochloric Memantine is made after drying；
(3) take hydroxypropyl methylcellulose to be dissolved in solvent and be configured to solution C, talcum powder is added into solution C stirring, obtains isolation bag
Clothing liquid；
(4) isolation coat liquid is coated to main medicament layer piller, separation layer piller is made after drying；
(5) take triethyl citrate and polyethylene glycol to be dissolved in solvent and be configured to solution D, ethyl cellulose is added into solution D
Stirring, obtains sustained release coating liquid；
(6) sustained release coating liquid is coated to separation layer piller, memantine sustained release pill is obtained after drying.
In the preparation method of above-mentioned memantine sustained release pill, following steps are specifically included；
(1), the preparation of main medicament layer piller；
A, hydroxypropyl methylcellulose is taken to add the container equipped with 80 DEG C~90 DEG C purified waters, stirring makes to disperse, and adds purifying
Water, it is stirring while adding, obtain A product；
B, polyethylene glycol and memantine are put in container, adds purified water dissolving, obtain B product；
C, A product are added in B product, stirs, then add talcum powder while stirring, talcum powder is uniformly dispersed, mistake
80 mesh sieves, obtain drug containing coating solution；
D, by blank capsule core, feed way is added in the material barrel of fluid bed by hand, is begun to warm up, and is protected to temperature of charge
When holding more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of blank capsule core, using peristaltic pump by drug containing coating solution to sky
White capsule core hydrojet；
E, drug containing coating solution have been sprayed completely, control material temperature is between 36 DEG C~40 DEG C, re-dry about 5-10 minutes,
Obtain the main medicament layer piller of hydrochloric Memantine；
(2), the preparation of separation layer piller；
A, hydroxypropyl methylcellulose is taken to add the container equipped with 80 DEG C~90 DEG C purified waters, stirring makes to disperse, let cool, Bian Lengjia
Side is stirred, and obtains C product；
B, talcum powder is put into C product and stirred, cross 80 mesh sieves, maintained agitator gentle agitation, obtain isolation coat liquid；
C, by main medicament layer piller, feed way is added in the material barrel of fluid bed by hand, is begun to warm up, to temperature of charge
When being maintained at more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of main medicament layer piller, using peristaltic pump by isolation coat liquid
To main medicament layer piller hydrojet；
D, isolation coat liquid have been sprayed completely, control material temperature is between 36 DEG C~40 DEG C, re-dry about 5-10 minutes,
Obtain separation layer piller；
(3), the preparation of memantine sustained release pill；
A, weigh triethyl citrate and polyethylene glycol is added in the container equipped with ethanol, be stirred to dissolve, add pure
Change water, obtain D product；
B, ethyl cellulose is slowly put into D product and stirred, cross 80 mesh sieves, maintained agitator gentle agitation, be sustained
Coating solution；
C, by separation layer piller, feed way is added in the material barrel of fluid bed by hand, is begun to warm up, to temperature of charge
When being maintained at more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of separation layer piller, using peristaltic pump by sustained release coating liquid
To separation layer piller hydrojet；
D, sustained release coating liquid have been sprayed completely, control material temperature is between 36 DEG C~40 DEG C, re-dry about 5-10 minutes,
Obtain memantine sustained release pill.
Compared with prior art, the present invention adds between the drug containing piller and sustained-release coating layer comprising memantine
One layer of isolation coat layer, solve the problems, such as that memantine medicine is easily prominent under high humidity environment and release, improve the stabilization of product
Property, the effect of ensure that product.Further, also to the component of each layer, proportioning and preparation technology, (including technique walks applicant
The parameter of rapid and each step) it is further defined, many factor synergies, burst drug release risk is minimally reduced,
So that the stability of product reaches optimal.The present invention also has a small volume, is not easy to be influenceed by food during drug administration, producer
Method is simple and easy, is suitable for industrialized production, there is larger application value.
Embodiment
With reference to embodiment, the present invention is further illustrated.
Embodiment 1：To study the separation layer influence to spansule dissolution under conditions of high humidity, two kinds of pillers, i.e. are prepared
Without separation layer (or isolation coat layer) drug containing piller A and having separation layer drug containing piller B, after pour into capsule and be sustained glue into corresponding
Capsule A and spansule B, while in the closed container for being put into relative humidity 92.5%, investigate 5,10 days dissolution results.
First, spansule A preparation
(1) prepared by the drug containing piller of memantine：
1.1, which weigh hydroxypropyl methylcellulose E3, adds the container equipped with 80 DEG C~90 DEG C purified waters, and stirring makes to disperse, added
Cold purified water, it is stirring while adding, obtain I；
1.2 put Macrogol 6000 and memantine in container, add purified water dissolving, obtain II.
1.3 again add (I) in (II), stir, and talcum powder is then added when stirring, and stirring makes talcum powder
It is uniformly dispersed.Coating solution crosses 80 mesh sieves, maintains agitator gentle agitation, standby.
1.4 by blank capsule core by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge protect
When holding more than 35 DEG C, atomizing pressure (1.6BAR) is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet.
1.5 treat that coating solution has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C, take out
Drug containing piller,
(2) sustained release coating process：
3.1 weigh triethyl citrate, and Macrogol 6000 is added in the container equipped with ethanol, is stirred to dissolve, and is added
Purified water, obtain I.
3.2 ethyl cellulose is slowly put into I in stirred 80 mesh sieve maintain agitator gentle agitation, it is standby.
3.3 by blank capsule core by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge protect
When holding more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet.
3.4 treat that coating solution has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C, take out
Slow-release pill A.
(3) slow-release pill A is obtained into spansule A by intermediates content filling capsule.
2nd, spansule B preparation
(1) prepared by the drug containing piller comprising memantine：
1.1, which weigh hydroxypropyl methylcellulose, adds the container equipped with 80 DEG C~90 DEG C purified waters, and stirring makes to disperse, added cold
Purified water, it is stirring while adding, obtain I.
1.2 put polyethylene glycol and memantine in container, add purified water dissolving, obtain II.
1.3 again add (I) in (II), stir, and talcum powder is then added when stirring, and stirring makes talcum powder scattered equal
It is even.Coating solution crosses 80 mesh sieves, maintains agitator gentle agitation, standby.
1.4 by blank capsule core by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge protect
When holding more than 35 DEG C, atomizing pressure (1.6BAR) is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet.
1.5 treat that coating solution has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C, take out
Drug containing piller.
(2) prepared by separation layer piller
2.1, which weigh hydroxypropyl methylcellulose E3, adds the container equipped with 80 DEG C~90 DEG C purified waters, and stirring makes to disperse, let cool,
The cold edged stirring in side, obtains I.
2.2 talcum powder is put into I in stirred 80 mesh sieve maintain agitator gentle agitation, it is standby.
2.3 by blank capsule core by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge protect
When holding more than 35 DEG C, atomizing pressure (1.6BAR) is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet.
2.4 treat that coating solution has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C, take out
Separation layer piller.
(3) sustained release coating process：
3.1 weigh triethyl citrate, and polyethylene glycol is added in the container equipped with ethanol, is stirred to dissolve, and adds purifying
Water, obtain I.
3.2 ethyl cellulose is slowly put into I in stirred 80 mesh sieve maintain agitator gentle agitation, it is standby.
3.3 by blank capsule core by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge protect
When holding more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet
3.4 treat that coating solution has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C, take out
Slow-release pill.
(4) slow-release pill B is obtained into spansule B by intermediates content filling capsule.
3rd, both the above spansule is put into 92.5% high humidity environment, sampled according to Chinese Pharmacopoeia within 0 day, 5,10 days
Dissolution detection method, using basket method, under 100 revs/min, in 900ml, 37 degree of pH1.2 cushioning liquid, to spansule
Carry out stripping curve detection.
As a result：Substantially it can be seen that spansule A and spansule B detected stripping curve at 0 day and is not different, still
Spansule A stripping curve is significantly faster than that 0 day after high humidity 5 days, 10 days, but spansule B stripping curve is almost
Do not change, it is possible thereby to show the separation layer protective effect superior to slow release effect.
Embodiment 2:The preparation method of Memantine hydrochloride sustained-release capsule：
(1)：It is prepared by the main medicament layer piller (i.e. drug containing piller) of hydrochloric Memantine：
1.1, which weigh hydroxypropyl cellulose, adds the container equipped with 80 DEG C~90 DEG C purified waters, and stirring makes to disperse, added cold
Purified water, it is stirring while adding, obtain I.
1.2 put polyethylene glycol and memantine in container, add purified water dissolving, obtain II.
1.3 again add (I) in (II), stir, and talcum powder is then added when stirring, and stirring makes talcum powder scattered equal
It is even, 80 mesh sieves are crossed, agitator gentle agitation is maintained, it is standby to obtain drug containing coating solution.
1.4 by blank capsule core by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge protect
When holding more than 35 DEG C, atomizing pressure (1.6BAR) is opened, adjusts the fluidized state of piller, using peristaltic pump by drug containing coating solution
To blank capsule core hydrojet.
1.5 treat that drug containing coating solution has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C,
Obtain the main medicament layer piller of hydrochloric Memantine.
(2) prepared by separation layer piller
2.1, which weigh hydroxypropyl cellulose EF, adds the container equipped with 80 DEG C~90 DEG C purified waters, and stirring makes to disperse, let cool,
The cold edged stirring in side, obtains I.
2.2 talcum powder is put into I in stirred 80 mesh sieve maintain agitator gentle agitation, it is standby to obtain isolation coat liquid.
2.3 by main medicament layer piller by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge
When being maintained at more than 35 DEG C, atomizing pressure (1.6BAR) is opened, adjusts the fluidized state of piller, you can peristaltic pump hydrojet is opened,
Using peristaltic pump by isolation coat liquid to main medicament layer piller hydrojet.
2.4 have sprayed isolation coat liquid completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C,
Obtain separation layer piller.
(3) preparation process of memantine sustained release pill：
3.1 weigh triethyl citrate, and polyethylene glycol is added in the container equipped with ethanol, is stirred to dissolve, and adds purifying
Water, obtain I.
3.2 ethyl cellulose is slowly put into I in stirred 80 mesh sieve maintain agitator gentle agitation, obtain sustained release coating
Liquid is standby.
3.3 by separation layer piller by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge
When being maintained at more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet, uses wriggling
Pump is by sustained release coating liquid to separation layer piller hydrojet.
3.4 treat that sustained release coating liquid has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C,
Take out memantine sustained release pill.
(4) memantine is sustained pill and obtains spansule by intermediates content filling capsule.
Embodiment 3：The preparation method of Memantine hydrochloride sustained-release capsule
(1) preparation of main medicament layer piller：
1.1, which weigh hydroxypropyl cellulose, adds the container equipped with 80 DEG C~90 DEG C purified waters, and stirring makes to disperse, added cold
Purified water, it is stirring while adding, obtain I.
1.2 put polyethylene glycol and memantine in container, add purified water dissolving, obtain II.
1.3 again add (I) in (II), stir, and talcum powder is then added when stirring, and stirring makes talcum powder scattered equal
It is even.80 mesh sieves are crossed, agitator gentle agitation is maintained, it is standby to obtain drug containing coating solution.
1.4 by blank capsule core by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge protect
When holding more than 35 DEG C, atomizing pressure (1.6BAR) is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet, makes
With peristaltic pump by drug containing coating solution to blank capsule core hydrojet.
1.5 treat that drug containing coating solution has sprayed completely, and control material temperature is between 36 DEG C~40 DEG C, about 5-10 points of re-dry
Clock, obtain the main medicament layer piller of hydrochloric Memantine.
(2) prepared by separation layer piller
2.1, which weigh hydroxypropyl cellulose EF, adds the container equipped with 80 DEG C~90 DEG C purified waters, and stirring makes to disperse, let cool,
The cold edged stirring in side, obtains I.
2.2 talcum powder is put into I in stirred 80 mesh sieve maintain agitator gentle agitation, it is standby.
2.3 by blank capsule core by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge protect
When holding more than 35 DEG C, atomizing pressure (1.6BAR) is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet, makes
With peristaltic pump by isolation coat liquid to main medicament layer piller hydrojet.
2.4 coating solutions to be isolated have sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C,
Obtain separation layer piller.
(3) preparation process of memantine sustained release pill：
3.1 weigh triethyl citrate, and polyethylene glycol is added in the container equipped with Surelease, is stirred to dissolve, and is added
Purified water, obtain I.
I stirred 80 mesh sieve is maintained agitator gentle agitation by 3.2, obtains sustained release coating liquid, standby.
3.3 by separation layer piller by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge
When being maintained at more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet, uses wriggling
Pump is by sustained release coating liquid to separation layer piller hydrojet.
3.4 treat that sustained release coating liquid has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C,
Obtain memantine sustained release pill.
(4) memantine sustained release pill will be obtained and obtain Memantine hydrochloride sustained-release capsule by intermediates content filling capsule.
Embodiment 4：The preparation method of Memantine hydrochloride sustained-release capsule
(1) preparation of drug containing piller：
Extrusion spheronization：Memantine, microcrystalline cellulose, HPMC are mixed, it is wet to make wetting agent with 25g water
Method is pelletized, and obtained wet granular obtains thickness and the appropriate bar of length by extruder, and bar obtains by spheronizator
Roundness and the appropriate piller of finish, it is 1% to be shaped with fixed that the piller is dried to moisture by 50 DEG C, crosses 25 mesh sieves
Obtain including the drug containing piller of memantine.
(2) prepared by separation layer piller
2.1, which weigh hydroxypropyl cellulose EF, adds the container equipped with 80 DEG C~90 DEG C purified waters, and stirring makes to disperse, let cool,
The cold edged stirring in side, obtains I.
2.2 talcum powder is put into I in stirred 80 mesh sieve maintain agitator gentle agitation, it is standby.
2.3 by the drug containing piller comprising memantine by hand feed way add fluid bed material barrel in, start
Heating, when being maintained at more than 35 DEG C to temperature of charge, atomizing pressure (1.6BAR) is opened, adjusts the fluidized state of piller, you can
Peristaltic pump hydrojet is opened, using peristaltic pump by sustained release coating liquid to separation layer piller hydrojet.
2.4 coating solutions to be isolated have sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C,
Take out separation layer piller.
(3) preparation process of memantine sustained release pill：
3.1 weigh triethyl citrate, and polyethylene glycol is added in the container equipped with Surelease, is stirred to dissolve, and is added
Purified water, obtain I.
I stirred 80 mesh sieve is maintained agitator gentle agitation by 3.2, obtains sustained release coating liquid, standby.
3.3 by separation layer piller by hand feed way add fluid bed material barrel in, begin to warm up, to temperature of charge
When being maintained at more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of piller, you can opens peristaltic pump hydrojet, uses wriggling
Pump is by sustained release coating liquid to separation layer piller hydrojet.
3.4 treat that sustained release coating liquid has sprayed completely, control material temperature re-dry about 5-10 minutes between 36 DEG C~40 DEG C,
Take out memantine sustained release pill.
(4) memantine is sustained pill and obtains Memantine hydrochloride sustained-release capsule by intermediates content filling capsule.
Claims (2)
1. memantine is sustained pill, it is characterised in that memantine sustained release pill from the inside to the outside successively by comprising
Drug containing piller, isolation coat layer and the sustained-release coating layer composition of memantine；
The drug containing piller forms by blank capsule core, and in main medicament layer of the outside of blank capsule core provided with hydrochloric Memantine；
The blank capsule core parts by weight are 80 parts, and the main medicament layer is composed of the following components by weight：28 parts of memantine, bonding
5 parts of 7 parts of agent HPMC E3,20 parts of diluent PEG6000 and antiplastering aid talcum powder；
The isolation coat layer is made up of 1 part of 7 parts of isolation coat material HPMC and talcum powder by weight；
The sustained-release coating layer is by weight by 29.4 parts of Sustained release coating materials ethyl cellulose 10cp, Macrogol 6000 11
2 parts of compositions of part and triethyl citrate.
2. the preparation method of the memantine sustained release pill described in a kind of claim 1, it is characterised in that including following step
Suddenly；（1）, main medicament layer piller preparation；
A, hydroxypropyl methylcellulose is taken to add the container equipped with 80 DEG C~90 DEG C purified waters, stirring makes to disperse, and adds purified water, side
Edged stirs, and obtains A product；
B, polyethylene glycol and memantine are put in container, adds purified water dissolving, obtain B product；
C, A product are added in B product, stirs, then add talcum powder while stirring, talcum powder is uniformly dispersed, cross 80 mesh
Sieve, obtains drug containing coating solution；
D, by blank capsule core, feed way is added in the material barrel of fluid bed by hand, is begun to warm up, is maintained to temperature of charge
At more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of blank capsule core, using peristaltic pump by drug containing coating solution to blank pill
Core hydrojet；
E, drug containing coating solution has been sprayed completely, control material temperature re-dry 5-10 minutes, is contained between 36 DEG C~40 DEG C
The main medicament layer piller of memantine；
（2）, separation layer piller preparation；
A, hydroxypropyl methylcellulose is taken to add the container equipped with 80 DEG C~90 DEG C purified waters, stirring makes to disperse, let cool, the cold edged in side stirs
Mix, obtain C product；
B, talcum powder is put into C product and stirred, cross 80 mesh sieves, maintained agitator gentle agitation, obtain isolation coat liquid；
C, by main medicament layer piller, feed way is added in the material barrel of fluid bed by hand, is begun to warm up, and is kept to temperature of charge
When more than 35 DEG C, atomizing pressure is opened, adjusts the fluidized state of main medicament layer piller, using peristaltic pump by isolation coat liquid to master
Medicine layer piller hydrojet；
D, isolation coat liquid has been sprayed completely, control material temperature is between 36 DEG C~40 DEG C, re-dry 5-10 minutes, obtain every
Absciss layer piller；
（3）, memantine sustained release pill preparation；
A, weigh triethyl citrate and polyethylene glycol added in the container equipped with ethanol, be stirred to dissolve, add purified water,
Obtain D product；
B, ethyl cellulose is slowly put into D product and stirred, cross 80 mesh sieves, maintained agitator gentle agitation, obtain sustained release coating
Liquid；
C, by separation layer piller, feed way is added in the material barrel of fluid bed by hand, is begun to warm up, and is kept to temperature of charge
When more than 35 DEG C, open atomizing pressure, adjust separation layer piller fluidized state, using peristaltic pump by sustained release coating liquid to every
Absciss layer piller hydrojet；
D, sustained release coating liquid has been sprayed completely, control material temperature re-dry 5-10 minutes, obtains salt between 36 DEG C~40 DEG C
Sour Memantine is sustained pill.
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Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104434855B (en) * | 2014-12-10 | 2017-02-01 | 哈药集团技术中心 | Memantine hydrochloride tablet and preparation method thereof |
| CN105326837A (en) * | 2015-10-09 | 2016-02-17 | 北京万全德众医药生物技术有限公司 | Memantine hydrochloride sustained release-donepezil quick release compound capsule |
| CN105769794B (en) * | 2016-04-03 | 2019-06-21 | 北京化工大学 | A kind of memantine sustained release pellet tablet and preparation method thereof |
| CN107773553A (en) * | 2016-08-26 | 2018-03-09 | 江苏先声药业有限公司 | A kind of memantine sustained release pellet and preparation method thereof |
| CN108066297B (en) * | 2016-11-16 | 2022-09-16 | 深圳万和制药有限公司 | Positioning release memantine orally disintegrating tablet composition for treating senile dementia |
| CN106581682A (en) * | 2016-12-09 | 2017-04-26 | 河南中帅医药科技股份有限公司 | Memantine hydrochloride/donepezil slow-release resin composition and preparation method thereof |
| CN106727439A (en) * | 2016-12-21 | 2017-05-31 | 河南中帅医药科技股份有限公司 | A kind of memantine is sustained donepezil quick-release compound capsule |
| CN109966269A (en) * | 2017-12-27 | 2019-07-05 | 江苏万邦生化医药集团有限责任公司 | A kind of Memantine hydrochloride slow-release pellet preparation and preparation method thereof |
| CN108969506A (en) * | 2018-09-11 | 2018-12-11 | 山东鲁抗医药股份有限公司 | A kind of memantine sustained release pellet and preparation method thereof |
| CN111568871A (en) * | 2020-03-23 | 2020-08-25 | 北京华氏开元医药科技有限公司 | Urapidil sustained release preparation and preparation method thereof |
| CN113546063A (en) * | 2020-04-26 | 2021-10-26 | 江苏天士力帝益药业有限公司 | Memantine hydrochloride sustained-release capsule 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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| CN103417491A (en) * | 2012-05-25 | 2013-12-04 | 杭州赛利药物研究所有限公司 | Memantine hydrochloride slow-release pellet preparation and preparation method thereof |
| CN103816135A (en) * | 2014-02-28 | 2014-05-28 | 广州新济药业科技有限公司 | Memantine hydrochloride sustained release preparation and preparing method thereof |
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| CA2607600A1 (en) * | 2005-06-16 | 2006-12-28 | Forest Laboratories, Inc. | Modified and immediate release memantine bead formulation |
| WO2012101653A2 (en) * | 2011-01-25 | 2012-08-02 | Cadila Healthcare Limited | Modified release pharmaceutical compositions memantine |
| CN103054826A (en) * | 2012-12-27 | 2013-04-24 | 北京阜康仁生物制药科技有限公司 | Orally disintegrating tablet of memantine hydrochloride sustained-release pellets and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103417491A (en) * | 2012-05-25 | 2013-12-04 | 杭州赛利药物研究所有限公司 | Memantine hydrochloride slow-release pellet preparation and preparation method thereof |
| CN103816135A (en) * | 2014-02-28 | 2014-05-28 | 广州新济药业科技有限公司 | Memantine hydrochloride sustained release preparation and preparing method thereof |
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