CN105434386B - A kind of sustained-release tablet containing highly-water-soluble active constituent and preparation method thereof - Google Patents
A kind of sustained-release tablet containing highly-water-soluble active constituent and preparation method thereof Download PDFInfo
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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
- A61K9/20—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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- 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
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
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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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
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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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- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
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Abstract
The invention belongs to pharmaceutical preparations technology fields, and in particular to a kind of sustained-release tablet containing highly-water-soluble active constituent and preparation method thereof.The component and its weight percent content of the sustained-release tablet are as follows：Highly-water-soluble active constituent 45%~70%, the first slow-release material 0.3%~4%, the second slow-release material 27%~51%, diluent 0~18%, lubricant 0.1%~1.0%, first slow-release material and the second slow-release material can be identical or different, and one or more in hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, carboxymethylcellulose calcium, povidone, carbomer, polyoxyethylene.Relative to existing sustained-release tablet, sustained-release tablet compressibility of the invention is good, and cost is relatively low, high-quality, and hardness will not decline after long-term storage.
Description
Technical field
The present invention relates to pharmaceutical preparations technology fields, and in particular to a kind of sustained-release tablet containing highly-water-soluble active constituent
And preparation method thereof.
Background technology
For highly-water-soluble active constituent, ordinary tablet has the disadvantages that：(1) highly-water-soluble active constituent is soluble in
Water, drug after oral administration dissolve out rapidly, and high amount of drug is only partially absorbed in small intestine site when by gastrointestinal tract, leads to biology
Availability is low；(2) highly-water-soluble activity component concentration is excessively high in gastrointestinal tract, and apparent stimulation is generated to gastrointestinal tract mucous
And generate the adverse reactions such as lactic acidosis；(3) ordinary tablet need to take orally often daily, and compliance is poor, forget that medication can influence
The effect of drug.Therefore, for highly-water-soluble active constituent, it is necessary to develop a kind of sustained release preparation.Sustained release preparation can ensure
Drug steadily discharges and extends the tail portion residence time, makes patient more comfortable；Due to using slow release method, drug dissolves in stomach
Greatly reduce, avoid the stimulation to stomach.
Since some highly-water-soluble active constituents are crystalline powder, poor fluidity, compressibility is excessively poor, in any pressure
Under all cannot be tabletted.It is further reduced by its compressibility after granulation, the tablet hardness range for making preparation is very narrow, unfavorable
In the quality control that commercialization produces greatly；Simultaneously due also to the commonly required high unit dose of highly-water-soluble active constituent is more than etc.
In 500mg/ pieces, available auxiliary material quantity space is limited.Therefore, the preparation method below sustained-release tablet generally use：
1st, tabletting after being pelletized using dry granulating machine.But since the compressibility of highly-water-soluble active constituent is excessively poor, lead to
Its compressibility further reduces after crossing dry granulation, and the tablet hardness range for making preparation is very narrow, and production is difficult to control.In addition,
Dry granulation process is complicated, and influence factor is various, and the compactibility and particle diameter distribution of particularly prepared particle can be to product matter
Amount generates significant impact, is unfavorable for being commercialized the quality control produced greatly.
2nd, using direct tablet compressing technique.It, can when being mixed with highly-water-soluble active constituent since the viscosity of slow-release material is very big
Mixing problem of non-uniform can occur；The grain size of slow-release material is small, and poor fluidity, recipe quantity is big, and grain size difference all influences prescription stream
The quality of dynamic property, and then cause tablet weight variation unstable.
3rd, using organic solvent.Organic solvent has been used in pelletization, explosion-proof arrange not only is used in production process
It applies, also the organic solvent in product is removed, the insecurity in production process and production cost has been significantly greatly increased
Greatly improve.
4th, release clothing film is controlled to reach slow release effect common tabletting packet.The invention has used in coating process
Solvent will not only use explosion precaution in production process, also the organic solvent in product is removed, be significantly greatly increased
Insecurity and production cost in production process greatly improve.In addition, manufacturing process is cumbersome.
5th, diluent is added in before tabletting, reduces the dosage of controlled-release material, achieve the purpose that Drug controlled release speed.For
Active component content is more than 40%, and for the very poor tablet of compressibility, after wet granulation, the compressibility of material is big
It is big to reduce, it is narrow to lead to the problem of hardness range.Even if adding in the diluent less than 5%, can not solve at all.
6th, using the rate of release of the controlled-release material of different stage control drug.The tablet batch that this preparation method obtains
Between rate of release difference it is big, its validity and safety will be influenced in this way.
Therefore, people are good for compliance, and drug release is steady, and compressibility is good, and for a long time store after hardness will not under
There are still demands for the higher sustained release preparation of quality of drop.
Invention content
In view of the above shortcomings of the prior art, the present invention provides a kind of new sustained releases containing highly-water-soluble active constituent
Tablet.
The present invention also provides the preparation methods of the above-mentioned sustained-release tablet containing highly-water-soluble active constituent.
The purpose of the present invention is achieved through the following technical solutions：
A kind of sustained-release tablet containing highly-water-soluble active constituent, wherein, the component of the sustained-release tablet and its weight hundred
Divide as follows than content：
First slow-release material and the second slow-release material can be identical or different, and selected from hydroxypropyl methylcellulose, hydroxyl
It is one or more in propyl cellulose, sodium carboxymethylcellulose, carboxymethylcellulose calcium, povidone, carbomer, polyoxyethylene.
First slow-release material and the second slow-release material substantially improve after specific Adding Way prepares particle
The dry jet mixing pile of mixed material, including compressibility and mobility.
Relative to existing sustained-release tablet, sustained-release tablet compressibility of the invention is good, in addition, cost is relatively low, high-quality, it is long
Hardness will not decline after phase storage.
Preferably, the sustained-release tablet is by including first adding highly-water-soluble active constituent and the first slow-release material mixing
Particle is made in water, then wet granule compression tablet method the step of pelletized with the second slow-release material and diluent is prepared.
For the highly-water-soluble active constituent excessively poor to compressibility, the present inventor is in an experiment it was unexpectedly observed that work as
When slow-release material is added in step by step in pelletization, obtained wet granular is uniform in size, will not be a large amount of high viscous because of using
It spends controlled-release material and a large amount of large crumb and fine powder, fast drying occurs, can accurately determine dry terminal.It can significantly improve slow
Hardness will not change after the compressibility of release tablet formulations and long-term placement, and prepared sustained-release tablet can effectively control releasing for drug
It puts.And it is possible thereby to overcome unqualified by tablet weight variation caused by plus slow release material in the prior art, preparation process is numerous
The defects of trivial, achieves unexpected advantageous effect.
Preferably, the weight ratio of first slow-release material and the second slow-release material is 1:10~90.First slow-release material
Content with the second slow-release material can act synergistically to ensure that tablet has in tableting processes in above-mentioned proportional region
The release that good formability and necessary hardness are become reconciled.
Preferably, second slow-release material is hydroxypropyl methylcellulose or is hypromellose cellulose content in 30% weight
Mixture more than amount.
The hydroxypropyl methylcellulose (such as hydroxypropyl methylcellulose K100MCR) belongs to the gel-type skeleton sustained release of water swelling
Material as main slow-release material, is used in mixed way individually or with other slow-release materials so that active constituent release is steady slow
Effect it is more preferable.
It is further preferred that second slow-release material be highly viscous hydroxypropyl methylcellulose (viscosity is 75000~
140000Pas), particularly preferably hydroxypropyl cellulose K100MCR.For the present invention, the hydroxypropyl of K100MCR ranks
Cellulose has the grain size and viscosity for being more suitable for preparing sustained-release tablet so that tablet has good hardness and the drug stablized to release
It puts, avoids tablet rupture in transportational process, the burst release at initial stage and the incomplete problem of later stage release.
Preferably, the one kind or more of the diluent in pregelatinized starch, microcrystalline cellulose, dextrin, calcium monohydrogen phosphate
Kind；The lubricant is magnesium stearate, calcium stearate, zinc stearate, aluminum stearate, stearic acid, magnesium carbonate, magnesia, talcum
It is one or more in powder, silica, superfine silica gel powder, polyethylene glycol, hydrogenated vegetable oil, sldium lauryl sulfate.The dilution
Agent has good mobility and compressibility, can further improve the hardness of tablet.
It is highly preferred that the diluent is microcrystalline cellulose；Its more preferable average grain diameter is 50 μm, is had with obtaining this
The surface area and cavernous structure and corresponding tabletting performance that invention sustained-release tablet property is adapted, can guarantee tablet
Hardness and cheap.The lubricant is magnesium stearate, it is a kind of widely applied excipient substance, cheap to be easy to get,
Do not influence product quality, such as hardness；In addition so that tablet surface is smooth.
Preferably, the component of the sustained-release tablet and its weight percent content are as follows：
Wherein, the weight ratio of first slow-release material and the second slow-release material is 1:10~50.
In the formula, the performance of sustained-release tablet obtained further improves.
Most preferably, the component of the sustained-release tablet and its weight percent content are as follows：
Wherein, the weight ratio of first slow-release material and the second slow-release material is 1:15~30.
In the formula, the performance of sustained-release tablet obtained further improves.
" the highly-water-soluble active constituent " is defined as the substance with therapeutic effect.
" the highly-water-soluble active constituent " refers to that active constituent is highly soluble in water, and solubility is more than 100mg/mL's in water
Substance.
An embodiment according to the present invention, the highly-water-soluble active constituent be selected from double valproic acids or its salt, niacin,
Melbine or its pharmaceutically acceptable derivates.
A kind of preparation method of the sustained-release tablet containing highly-water-soluble active constituent, includes the following steps：
(1) it by highly-water-soluble active constituent and the first slow-release material mixing, adds in water and particle is made；Then it is slow to add in second
It releases material and diluent is pelletized to obtain wet granular；
(2) above-mentioned wet granular is dried to obtain dry particl, whole grain then is carried out to dry particl；
(3) particle after above-mentioned whole grain and lubricant are uniformly mixed so as to obtain material, then tabletting to obtain the final product.
Preferably, in step (2), the aperture of the sieve of the whole grain is 0.6~2.5mm, more preferable 1.0~2.0mm, into
The preferred 1.5mm of one step.Such as pelletizing machine progress can be used in the step.
Preferably, the lubricant is sieved in advance, sieve mesh number be 16~30 mesh, more preferably 16~25 mesh, into
One step is preferably 20 mesh.
In the sustained-release tablet containing highly-water-soluble active constituent of the present invention, the content of highly-water-soluble active constituent is very high,
Therefore one timing of highly-water-soluble active component content, smaller, patient swallows easily, and administration compliance is good.
The content specification of the sustained-release tablet containing highly-water-soluble active constituent of the present invention usually can be according to administering mode
It needs flexibly to set.The absolute content of highly-water-soluble active constituent is generally 500mg/ pieces~1000mg/ pieces.
Unless otherwise indicated, percentage of the present invention " % " is the weight percent based on unitary tablet.Also,
In unit formulation, the sum of each component degree is 100%.
The prescription compressibility of the sustained-release tablet of the present invention is good, ensures that active constituent rate of release is steady, makes tablet quality more
It is guaranteed.
The preparation method technique of the present invention is simpler, and cost is relatively low, and the sustained-release tablet being prepared has with existing drug
Comparable therapeutic effect.
The various auxiliary materials that the sustained-release tablet of the present invention uses, can very easily buy, and cheap on the market,
So the tablet of the present invention is at low cost, it can significantly mitigate the medication burden of patient.In addition, the preparation process of the present invention is simple, it can
Control property is strong, easy to operate.
Description of the drawings
Fig. 1 is that sustained-release tablet prepared by embodiment 1 and the former dissolution for grinding medicine in pH6.8 phosphate-buffered liquid mediums are bent
Line.
Specific embodiment
The invention discloses good sustained-release tablets containing highly-water-soluble active constituent of a kind of compressibility and preparation method thereof.
Based on the description of more than invention content, those skilled in the art can be comprehensively with the application of the invention, all same principles or similar
Change be regarded as being included within the scope of the present invention.
It is just provided by the invention slow containing highly-water-soluble active constituent below in order to be better understood from and illustrate the present invention
Release tablet formulations and preparation method thereof provide exemplary illustration, but it is understood not to the limitation to invention content.
Device therefor instrument mainly includes in following embodiment：
G20 type wet mixing pelletizers；BSL-25 type mixing machines；FZB type crushing and pelletizing machines；ZP10A type tablet press machines；YD-
35 tablet hardness instruments；RC806 digestion instruments.
Embodiment 1
Prescription is as shown in table 1：
Table 1：1000 diabecron sustained-release tablet (750mg/ pieces) prescriptions
It is according to recipe quantity in upper table that highly-water-soluble active ingredient hydrochloric acid melbine and the first slow-release material carboxymethyl is fine
The plain sodium of dimension is placed in wet mixing pelletizer, and setting mixing speed is 200~250 revs/min, and cutter speed is 2000~3000
Rev/min, the particle that suitable size is made in appropriate purified water is gradually added into after dry-mixed, then adds in the second slow-release material hydroxypropyl first fibre
Dimension element K100MCR pelletizes in pot of pelletizing.Wet granular obtained moves to drying in fluid bed, and temperature of charge is 50 DEG C, it
The sieve for crossing 1.5mm afterwards obtains the particle containing Metformin hydrochloride.By the lubricant of recipe quantity cross 20 mesh sieve after and above-mentioned salt
Sour melbine particle is uniformly mixed, the tablet of adjustment compression force compacting different hardness.
Embodiment 2
Prescription is as shown in table 2：
Table 2：1000 niacin slow-release tablet (750mg/ pieces) prescriptions
Sustained release tablets are prepared using preparation method same as Example 1.
Embodiment 3
Prescription is as shown in table 3：
Table 3：1000 Divalproex sodium sustained-release tablet (500mg/ pieces) prescriptions
Other than the second slow-release material and diluent are added in together, using preparation method system same as Example 1
Standby sustained release tablets.
Embodiment 4
Prescription is as shown in table 4：
Table 4：1000 niacin slow-release tablet (750mg/ pieces) prescriptions
Sustained release tablets are prepared using preparation method same as Example 1.
Embodiment 5
Prescription is as shown in table 5：
Table 5：1000 Divalproex sodium sustained-release tablet (500mg/ pieces) prescriptions
Other than two kind of second slow-release material is added in together, prepared using preparation method same as Example 1 slow
Release piece.
Comparative example 1
Prescription is identical with table 1 in embodiment 1.Preparation method is：
According to recipe quantity in table 1 by highly-water-soluble active ingredient hydrochloric acid melbine, the first slow-release material carboxymethyl cellulose
Plain sodium and the second slow-release material hydroxypropyl methylcellulose K100MCR are placed in wet mixing pelletizer, setting mixing speed for 200~
250 revs/min, cutter speed is 2000~3000 revs/min, appropriate purified water is gradually added into after dry-mixed, particle is made, obtained
Wet granular moves to drying in fluid bed, and temperature of charge is 50 DEG C, and the sieve for crossing 1.5mm later is obtained containing Metformin hydrochloride
Particle.The lubricant of recipe quantity is crossed after 20 mesh sieve and is uniformly mixed with above-mentioned Metformin hydrochloride particle, adjustment compression force compacting
The tablet of different hardness.
1 embodiment 1 of experimental example grinds medicine sustained-release tablet dissolution determination with original
In United States Pharmacopeia 37 editions the dissolving-out method of diabecron sustained-release tablet be using dissolution method (the second method,
Paddle method)：
Digestion instrument：Tian Fa Science and Technology Ltd.s of University Of Tianjin RC806；
Dissolution medium：PH6.8 phosphate buffers, 1000ml；
Chromatographic column：Agilent, Zorbax SB C18,4.6mm x 150mm, 5 μm；
Dissolution medium temperature：37℃；
The manufacturer that original grinds medicine is：Bristol Myers Squibb.
Method 2 (paddle method)：100rpm；Time：1 hour, 2 hours and 10 hours.
As a result comparison and conclusion：
Fig. 1 is that diabecron sustained-release tablet agent prepared by embodiment 1 and original grind medicine in pH6.8 phosphate-buffered liquid mediums
In Dissolution profiles figure.Its middle polyline A is the Dissolution profiles that original grinds medicine, and broken line B is sustained-release tablet prepared by embodiment 1
Dissolution profiles.
As shown in Figure 1, the Dissolution profiles of diabecron sustained-release tablet prepared by the present invention and the former dissolution rate for grinding medicine
Curvilinear trend is identical, similar factors 74.Illustrate that the dissolution rate of the sustained-release tablet of the invention containing Metformin hydrochloride is ground with original
Medicine is closely similar, therefore the two can reach closely similar therapeutic effect.But the present invention is slow containing Metformin hydrochloride
Release tablet formulations preparation method is simple, easily realizes, cost is substantially reduced.
Dissolution determination is carried out to sustained-release tablet prepared by embodiment 2~5, it is also closely similar that dissolution rate with original grinds medicine.
The measure of 2 embodiment 1 of experimental example, 1 sustained-release tablet compressibility of embodiment 3, embodiment 5 and comparative example
Example 1,3 and each 10 of the product of comparative example 1, are placed in hardness tester, carry out Determination of Hardness.
The tablet placement of Example 5 carried out hardness test after 12 months under room temperature.
According to 2010 editions annex VE tablet friability inspection techniques of Chinese Pharmacopoeia：10 are taken, the powder to come off is blown away with hair-dryer
End, precise weighing are put in cylinder, are rotated 100 times.It takes out, powder, precise weighing is removed with method.Counting loss weight obtains crisp
Broken number of degrees value.As a result it is as follows.
Table 6：1 sustained-release tablet hardness range of embodiment
Table 7：3 sustained-release tablet hardness range of embodiment
Table 8：1 sustained-release tablet hardness range of comparative example
Table 9：The embodiment 5 sustained-release tablet room temperature hardness test result of 12 months
As a result comparison and conclusion：
From table 6 and table 7 as it can be seen that in the preparation method of sustained-release tablet of the present invention, the first slow-release material and the second slow-release material
After adding in granulation by several times, obtained always mixed powder has very wide hardness range, illustrates it with good compressibility.Therefore, when
First slow-release material and the second slow-release material add in granulation by several times, and the compressibility and release of tablet are fine.
As seen from Table 8, after slow-release material adds in granulation simultaneously, obtained always mixed powder adjustment compression force cannot all obtain friability
Qualified hardness range is spent, illustrates that its preparation process is not suitable for.
As seen from Table 9, after the sustained-release tablet that preparation method of the present invention obtains is placed for a long time, hardness will not change,
Illustrate that its preparation process is suitable.
Claims (10)
- A kind of 1. sustained-release tablet containing highly-water-soluble active constituent, which is characterized in that the component of the sustained-release tablet and its again It is as follows to measure degree：First slow-release material is selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, carboxymethyl cellulose It is one or more in calcium, povidone, carbomer, polyoxyethylene；The sustained-release tablet be by including first adding water that particle is made highly-water-soluble active constituent and the first slow-release material mixing, The wet granule compression tablet method for the step of being pelletized again with the second slow-release material and diluent is prepared；The weight ratio of first slow-release material and the second slow-release material is 1:10~90；Second slow-release material is hydroxypropyl methylcellulose or is mixing of the hypromellose cellulose content more than 30% weight Object.
- 2. the sustained-release tablet according to claim 1 containing highly-water-soluble active constituent, which is characterized in that the diluent It is one or more in pregelatinized starch, microcrystalline cellulose, dextrin, calcium monohydrogen phosphate；The lubricant be selected from magnesium stearate, Calcium stearate, zinc stearate, aluminum stearate, stearic acid, magnesium carbonate, magnesia, talcum powder, silica, superfine silica gel powder, poly- second It is one or more in glycol, hydrogenated vegetable oil, sldium lauryl sulfate；The highly-water-soluble active constituent be selected from double valproic acids or Its salt, niacin or melbine.
- 3. the sustained-release tablet according to claim 1 containing highly-water-soluble active constituent, which is characterized in that described second is slow Material is released as highly viscous hydroxypropyl methylcellulose, the diluent is microcrystalline cellulose, and the lubricant is magnesium stearate.
- 4. the sustained-release tablet according to claim 3 containing highly-water-soluble active constituent, which is characterized in that described second is slow Material is released as hydroxypropyl cellulose K100MCR.
- 5. the sustained-release tablet according to claim 1 containing highly-water-soluble active constituent, which is characterized in that the sustained release tablets The component and its weight percent content of agent are as follows：Wherein, the weight ratio of first slow-release material and the second slow-release material is 1:10~50.
- 6. the sustained-release tablet according to claim 1 containing highly-water-soluble active constituent, which is characterized in that the sustained release tablets The component and its weight percent content of agent are as follows：Wherein, the weight ratio of first slow-release material and the second slow-release material is 1:15~30.
- 7. a kind of preparation method of the sustained-release tablet according to any one of claims 1 to 6 containing highly-water-soluble active constituent, It is characterized by comprising the following steps：(1) it by highly-water-soluble active constituent and the first slow-release material mixing, adds in water and particle is made；Then the second sustained release material is added in Material and diluent are pelletized to obtain wet granular；(2) above-mentioned wet granular is dried to obtain dry particl, whole grain then is carried out to dry particl；(3) particle after above-mentioned whole grain and lubricant are uniformly mixed so as to obtain material, then tabletting to obtain the final product.
- 8. the preparation method of the sustained-release tablet according to claim 7 containing highly-water-soluble active constituent, which is characterized in that In step (2), the aperture of the sieve of the whole grain is 0.6~2.5mm；The lubricant is sieved in advance, and sieve mesh number is 16~30 mesh.
- 9. the preparation method of the sustained-release tablet according to claim 8 containing highly-water-soluble active constituent, which is characterized in that In step (2), the aperture of the sieve of the whole grain is 1.0~2.0mm；The lubricant is sieved in advance, and sieve mesh number is 16~25 mesh.
- 10. the preparation method of the sustained-release tablet according to claim 9 containing highly-water-soluble active constituent, feature exist In in step (2), the aperture of the sieve of the whole grain is 1.5mm；The lubricant is sieved in advance, sieve mesh number 20 Mesh.
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| CN107049980A (en) * | 2017-04-01 | 2017-08-18 | 重庆康刻尔制药有限公司 | A kind of diabecron sustained-release tablet and preparation method thereof |
| CN107412182B (en) * | 2017-04-01 | 2020-11-13 | 重庆康刻尔制药股份有限公司 | Preparation method of metformin hydrochloride sustained-release tablets |
| CN111588701B (en) * | 2020-05-25 | 2021-04-23 | 上海普康药业有限公司 | Metformin hydrochloride sustained release tablet and preparation method thereof |
| CN112168796B (en) * | 2020-09-28 | 2022-10-25 | 北京诺康达医药科技股份有限公司 | Controlled-release drug sustained-release preparation of biphasic sustained-release system and preparation method thereof |
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| CN1850033A (en) * | 2006-03-07 | 2006-10-25 | 中国药科大学 | Water soluble anti-cancer medicine slow-release fiber preparation and preparing method therefor |
| CN101288652A (en) * | 2007-09-30 | 2008-10-22 | 西北工业大学 | Water-soluble drug sustained-release tablet and preparation method thereof |
| CN101444486A (en) * | 2008-06-20 | 2009-06-03 | 广东药学院 | Water-soluble drug sustained-release microsphere and preparation method and applications thereof |
| CN101518518A (en) * | 2008-12-12 | 2009-09-02 | 山东京卫制药有限公司 | Niacin simvastatin sustained-release preparation and preparation method thereof |
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Address after: Haikou standard structure building 570, No. 3113, Haikou Industrial Park, Haikou, Haixin high tech Zone, Hainan Province Patentee after: Huayi Taikang Pharmaceutical Co.,Ltd. Address before: 571100 Haikou City, Hainan Province, 273 Nanhai Avenue Haikou High-tech Zone D light steel structure standard industrial plant west side Patentee before: HAINAN VISUM PHARMACEUTICAL Co.,Ltd. |
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