CN109908096A - A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof - Google Patents
A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof Download PDFInfo
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- CN109908096A CN109908096A CN201711313479.4A CN201711313479A CN109908096A CN 109908096 A CN109908096 A CN 109908096A CN 201711313479 A CN201711313479 A CN 201711313479A CN 109908096 A CN109908096 A CN 109908096A
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- trimetazidine hydrochloride
- hydroxypropyl methylcellulose
- sustained
- release tablets
- release
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Abstract
This application discloses a kind of trimetazidine hydrochloride sustained-release tablets, including Trimetazidine Hydrochloride, sustained-release matrix material, filler, adhesive and lubricant, and the sustained-release matrix material is the mixture of different viscosities hydroxypropyl methylcellulose.The Trimetazidine Hydrochloride Tablets in healthy of the application have compared with the burst release for solving Trimetazidine Hydrochloride early period accomplish that drug steadily discharges, and solve that Trimetazidine Hydrochloride Tablets in healthy stability is poor, degradable disadvantage improves Trimetazidine Hydrochloride Tablets in healthy stability.
Description
Technical field
The application belongs to field of pharmaceutical preparations, more specifically, this application involves a kind of trimetazidine hydrochloride sustained-release tablets and
Preparation method.
Background technique
Trimetazidine (Trimetazidine) chemical name is 1- (2,3,4- trimethoxy benzyl) piperazine, is first
3- ketone Acyl-CoA thiolase inhibitor (3-KAT), it can inhibit fatty acid (FFA) to aoxidize, and stimulation grape is glycoxidative, and
Confrontation Ischemic Myocardial Cells have protective effect to a certain extent.Trimetazidine Hydrochloride is widely used in angina pectoris hair in recent years
The prophylactic treatment of work and the complementary symptomatic treatment of dizziness and tinnitus.
External listing trimetazidine hydrochloride sustained-release tablets, trade name Vastarel MR reach maximum at present after 5 hours oral
Concentration, time of the blood concentration not less than 75% is more than 24 hours, reaches stable state within 60 hours.The daily single of conventional tablet takes agent
Amount is 20mg, need to be taken daily 3 times, is prepared into sustained-release tablet and can reduce and takes number, improves patient's compliance.
Patent EP1108424A1 describes a kind of substrate tablet that can discharge Trimetazidine for a long time, it is characterised in that base
Matter piece is realized by hypromellose, but a kind of viscosity hypromellose is applied alone, and drug is caused to be released, and is dissolved out
It is not sufficiently stable, it is incompatible as adhesive and Trimetazidine Hydrochloride using povidone, cause trimetazidine hydrochloride sustained-release tablets to be stablized
Property the degradation of difference long-term experiment it is serious.
Patent CN1124140A is described using ethyl cellulose or the film controlling type of polymethacrylic acid polymer sustained release system
Agent.Although the composition release time is long, drug discharged about 75% at 16 hours, and release is incomplete.
Patent CN1994280A, which is described, prepares Trimetazidine Hydrochloride pellet using centrifugal granulating or extrusion spheronization method, fluidisation
Reach slow releasing function after bed coating, this step of preparation process is cumbersome, is unfavorable for industrialized production.
Patent WO2009066315A2 describes a kind of without containing the Trimetazidine of cellulose or derivatives thereof or its salt
Slow releasing composition.This application uses the povidone solution of isopropanol as adhesive, the tabletting by the way of wet granulation.It is this
Mode increases the residual of organic solvent in tablet, not only not environmentally but also has improved cost, and early period, release was very fast.
Patent CN102670537A describes a kind of using polyvinyl acetate and povidone mixture and ethyl cellulose
Mixture sustained release tablets are made as sustained-release matrix material.Trimetazidine Hydrochloride Tablets in healthy stability is poor in this application, and degradable lacks
Point.
In conclusion since above-mentioned deficiency exists in the prior art, spy proposes this application.
Summary of the invention
The purpose of the application is, in view of the deficiencies of the prior art, provides a kind of trimetazidine hydrochloride sustained-release tablets.The sustained release
Piece, which does sustained-release matrix material using different viscosities hydroxypropyl methylcellulose, can control the burst release of Trimetazidine Hydrochloride early period, reach
Steady releasing effect.
To achieve the goals above, the application adopts the following technical scheme that
A kind of trimetazidine hydrochloride sustained-release tablets, including Trimetazidine Hydrochloride, sustained-release matrix material, filler, adhesive and
Lubricant, which is characterized in that the sustained-release matrix material is the mixture of different viscosities hydroxypropyl methylcellulose.
Preferably, the different viscosities hydroxypropyl methylcellulose mixture refers to low viscosity hydroxypropyl methylcellulose and high viscosity hydroxyl
The mixing of third methylcellulose, and the weight ratio of low viscosity hydroxypropyl first fiber number dimension element and high viscosity hydroxypropyl methylcellulose is 1/5-1/3；
Preferably 1/4.
Preferably, the low viscosity hydroxypropyl methylcellulose viscosity is 2.0~100mPa.s, preferably hydroxypropyl methylcellulose E50；
The high viscosity hydroxypropyl methylcellulose viscosity is 3000~120000mPa.s, preferably hydroxypropyl methylcellulose E4M.
Preferably, in the trimetazidine hydrochloride sustained-release tablets, by weight percentage, the content of each component are as follows:
15-30% Trimetazidine Hydrochloride；
15-65% filler；
2-10% adhesive；
20-65% hydroxypropyl methylcellulose mixture；
0.1-1% lubricant.
Preferably, in the trimetazidine hydrochloride sustained-release tablets, by weight percentage, the content of each component are as follows:
15-20% Trimetazidine Hydrochloride；
20-50% filler；
2-8% adhesive；
30-55% hydroxypropyl methylcellulose mixture；
0.3-0.6% lubricant.
Preferably, the filler is one or more of calcium hydrogen phosphate hydrate, microcrystalline cellulose or lactose.
Preferably, described adhesive is hydroxypropyl methylcellulose, preferably hydroxypropyl methylcellulose E50.
Preferably, the lubricant is one of magnesium stearate, talcum powder, colloidal silicon dioxide or superfine silica gel powder or several
Kind.
The trimetazidine hydrochloride sustained-release tablets of the application do sustained-release matrix material using the mixing of different viscosities hydroxypropyl methylcellulose
The burst release that Trimetazidine Hydrochloride early period can be controlled reaches steady releasing effect；Adhesive is done using hydroxypropyl methylcellulose, and
Routine is made adhesive with povidone and is compared, and avoids Trimetazidine Hydrochloride after placing for a long time from degrading, guarantees trimetazidine hydrochloride sustained-release
Tablet stability, Trimetazidine Hydrochloride, filler and adhesive are with mixture after purified water wet granulation into framework material tabletting
Technique prepares sustained release tablets, avoids that organic solvent is added, is suitble to industrialized production.
Trimetazidine Hydrochloride easily dissolves in water, and solubility is greater than 1000mg/mL, therefore controls high solubility agents
Burst release be the key that the application.So-called burst release just refers to the drug bolus release that slow, controlled release preparation occurs at release initial stage
Phenomenon.
Trimetazidine hydrochloride sustained-release tablets described herein do sustained-release matrix material using different viscosities hydroxypropyl methylcellulose
The burst release that Trimetazidine Hydrochloride early period can be controlled reaches steady releasing effect.The sustained-release matrix material hydroxypropyl first is fine
It ties up plain mixture and accounts for sustained release tablets total weight 20-65%, wherein hydroxypropyl methylcellulose E50 and hydroxypropyl methylcellulose E4M ratio 1/5-
1/3, more preferable 1/4, why determine that such amount ranges are because of low viscosity hydroxypropyl methylcellulose in sustained-release matrix material
The burst release that gel prevents drug can be formed in drug release initial stage rapid aquation, high viscosity hydroxypropyl methylcellulose can be better
Control the steady release of later period drug.
Trimetazidine hydrochloride sustained-release tablets described herein make adhesive using hydroxypropyl methylcellulose, and preferably hydroxypropyl first is fine
Tie up element E50, dosage for sustained release tablets total weight 2-10%, preferably 4%, avoid using polyvinylpyrrolidone as adhesive,
To avoid Trimetazidine Hydrochloride after placing for a long time from degrading, trimetazidine hydrochloride sustained-release tablets stability ensure that.
The another object of the application is, provides a kind of preparation method of trimetazidine hydrochloride sustained-release tablets.
To achieve the goals above, the application adopts the following technical scheme that
A kind of preparation method of trimetazidine hydrochloride sustained-release tablets, which is characterized in that the preparation method includes by salt love song
He carries out wet granulation at piperazine, filler and adhesive mixing to beauty, and then additional framework material and mix lubricant, carry out tabletting packet
Clothing to get arrive the trimetazidine hydrochloride sustained-release tablets.
Preferably, the method specifically comprises the following steps:
(1) Trimetazidine Hydrochloride is uniformly mixed with filler and adhesive；
(2) purified water wet granulation is used, fluidized bed drying obtains dry particle；
(3) above-mentioned dry particle mixed with hydroxypropyl methylcellulose, finally lubricant added to mix；
(4) tabletting, coating.
The preparation method of trimetazidine hydrochloride sustained-release tablets described herein, with the technique system of purified water wet granule compression tablet
It is standby, it avoids that organic solvent is added, environmental protection and saving, process stabilizing are suitble to industrialized production.And trimetazidine hydrochloride sustained-release obtained
Tablet quality is stablized, and dissolution is steady.
Specific embodiment
The application is described in detail below with reference to embodiment, but the application is not limited to these embodiments.
Unless otherwise instructed, the raw material in embodiments herein is bought by commercial sources,
Wherein Trimetazidine Hydrochloride purchase is bought from Wuhan Wuyao Pharmaceutical Co., Ltd, hydroxypropyl methylcellulose from DOW Chemical
Company, other auxiliary materials are common medicinal supplementary material.
Obtained trimetazidine hydrochloride sustained-release tablets measure hardness with YD-20 hardness analyzer in embodiment.
Obtained trimetazidine hydrochloride sustained-release tablets Elite8 digestion instrument and U3000 type high performance liquid chromatography in embodiment
Instrument measures release.
Embodiment 1
1, prescription
Preparation process
(1) recipe quantity Trimetazidine Hydrochloride, calcium monohydrogen phosphate and polyvinylpyrrolidone are uniformly mixed.
(2) add appropriate purified water wet granulation, fluidized bed drying.
(3) particle is made in step (2) and recipe quantity hydroxypropyl methylcellulose E50, hydroxypropyl methylcellulose E4M is uniformly mixed,
Magnesium stearate is added to be uniformly mixed；
(4) the mixture tabletting that obtains step (3), non-functional coatings.
It is as shown in the table that the phosphate buffer that the sample that embodiment 1 obtains is put in pH6.8 is measured into release:
The release profiles for investigating the trimetazidine hydrochloride sustained-release tablets that embodiment 1 obtains can be seen that with different viscosities hydroxypropyl
The mixture of methylcellulose does the better Drug controlled release of framework material energy, prevents burst drug release.
Embodiment 2
Prescription:
Preparation process:
(1) recipe quantity Trimetazidine Hydrochloride, calcium monohydrogen phosphate and polyvinylpyrrolidone are uniformly mixed.
(2) add appropriate purified water wet granulation, fluidized bed drying.
(3) particle is made in step (2) and recipe quantity hydroxypropyl methylcellulose E50, hydroxypropyl methylcellulose E4M is uniformly mixed,
Magnesium stearate is added to be uniformly mixed；
(4) the mixture tabletting that obtains step (3), non-functional coatings.
The phosphate buffer that the sample that embodiment 2 obtains is put in pH6.8 is measured into release are as follows:
Variety classes adhesive known to the release profiles for the trimetazidine hydrochloride sustained-release tablets that embodiment 2 obtains is investigated to hydrochloric acid
The release of Trimetazidine sustained release tablets influences little.
Sample in embodiment 2 is carried out to accelerate 6 months related substance investigation results as shown in the table:
| It is total miscellaneous | 0 day | Accelerate January | Accelerate 2 months | Accelerate 3 days | Accelerate 6 months |
| Prescription 3 | 0.12 | 0.12 | 0.13 | 0.14 | 0.15 |
| Prescription 4 | 0.13 | 0.13 | 0.14 | 0.16 | 0.17 |
| Prescription 5 | 0.13 | 0.23 | 0.31 | 0.43 | 0.56 |
It can be seen that with hydroxypropyl methylcellulose by accelerating 6 months related substances to investigate result as adhesive implementation
Example has preferable stability.
Embodiment 3
1, prescription
Preparation process
(1) recipe quantity Trimetazidine Hydrochloride, calcium monohydrogen phosphate and adhesive are uniformly mixed.
(2) add appropriate purified water wet granulation, fluidized bed drying.
(3) particle is made in step (2) and recipe quantity hydroxypropyl methylcellulose E50, hydroxypropyl methylcellulose E4M is uniformly mixed,
Magnesium stearate is added to be uniformly mixed；
(4) the mixture tabletting that obtains step (3), non-functional coatings.
The above is only several embodiments of the application, not does any type of limitation to the application, although this Shen
Please disclosed as above with preferred embodiment, however not to limit the application, any person skilled in the art is not taking off
In the range of technical scheme, a little variation or modification are made using the technology contents of the disclosure above and is equal to
Case study on implementation is imitated, is belonged in technical proposal scope.
Claims (10)
1. a kind of trimetazidine hydrochloride sustained-release tablets, including Trimetazidine Hydrochloride, sustained-release matrix material, filler, adhesive and profit
Lubrication prescription, which is characterized in that the sustained-release matrix material is the mixture of different viscosities hydroxypropyl methylcellulose.
2. trimetazidine hydrochloride sustained-release tablets according to claim 1, which is characterized in that the different viscosities hypromellose
Plain mixture refers to the mixing of low viscosity hydroxypropyl methylcellulose and high viscosity hydroxypropyl methylcellulose, and low viscosity hydroxypropyl first fiber number is tieed up
The weight ratio of element and high viscosity hydroxypropyl methylcellulose is 1/5-1/3；Preferably 1/4.
3. trimetazidine hydrochloride sustained-release tablets according to claim 2, which is characterized in that the low viscosity hydroxypropyl methylcellulose
Viscosity is 2.0~100mPa.s, preferably hydroxypropyl methylcellulose E50；The high viscosity hydroxypropyl methylcellulose viscosity be 3000~
120000mPa.s preferably hydroxypropyl methylcellulose E4M.
4. trimetazidine hydrochloride sustained-release tablets described in any one of -3 according to claim 1, which is characterized in that the salt love song
In his beautiful piperazine sustained release tablets, by weight percentage, the content of each component are as follows:
15-30% Trimetazidine Hydrochloride；
15-65% filler；
2-10% adhesive；
20-65% hydroxypropyl methylcellulose mixture；
0.1-1% lubricant.
5. trimetazidine hydrochloride sustained-release tablets according to claim 4, which is characterized in that the trimetazidine hydrochloride sustained-release tablets
In, by weight percentage, preferably each component contains:
15-20% Trimetazidine Hydrochloride；
20-50% filler；
2-8% adhesive；
30-55% hydroxypropyl methylcellulose mixture；
0.3-0.6% lubricant.
6. trimetazidine hydrochloride sustained-release tablets described according to claim 1 or 2 or 3 or 5, which is characterized in that the filler is
One or more of calcium hydrogen phosphate hydrate, microcrystalline cellulose or lactose.
7. trimetazidine hydrochloride sustained-release tablets described according to claim 1 or 2 or 3 or 5, which is characterized in that described adhesive is
Hydroxypropyl methylcellulose, preferably hydroxypropyl methylcellulose E50.
8. trimetazidine hydrochloride sustained-release tablets described according to claim 1 or 2 or 3 or 5, which is characterized in that the lubricant is
One or more of magnesium stearate, talcum powder, colloidal silicon dioxide or superfine silica gel powder.
9. a kind of preparation method of the trimetazidine hydrochloride sustained-release tablets as described in any one of claim 1-8, feature exist
In the preparation method includes mixing Trimetazidine Hydrochloride, filler and adhesive to carry out wet granulation, then additional skeleton
Material and mix lubricant carry out compress tablet coating to get the trimetazidine hydrochloride sustained-release tablets are arrived.
10. preparation method according to claim 9, which is characterized in that the method specifically comprises the following steps:
(1) Trimetazidine Hydrochloride is uniformly mixed with filler and adhesive；
(2) purified water wet granulation is used, fluidized bed drying obtains dry particle；
(3) above-mentioned dry particle mixed with hydroxypropyl methylcellulose, finally lubricant added to mix；
(4) tabletting, coating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711313479.4A CN109908096A (en) | 2017-12-12 | 2017-12-12 | A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711313479.4A CN109908096A (en) | 2017-12-12 | 2017-12-12 | A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof |
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| CN201711313479.4A Pending CN109908096A (en) | 2017-12-12 | 2017-12-12 | A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110623934A (en) * | 2019-09-26 | 2019-12-31 | 杭州百诚医药科技股份有限公司 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
| CN112315942A (en) * | 2020-11-04 | 2021-02-05 | 南京康川济医药科技有限公司 | Trimetazidine hydrochloride sustained release preparation and preparation method thereof |
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| EP1108424A1 (en) * | 1999-12-17 | 2001-06-20 | Adir Et Compagnie | Matrix tablet for sustained release of trimetazidine after oral administration |
| US20020006435A1 (en) * | 2000-01-27 | 2002-01-17 | Samuels Paul J. | Transdermal anesthetic and vasodilator composition and methods for topical administration |
| WO2009034541A9 (en) * | 2007-09-11 | 2009-12-30 | Ranbaxy Laboratories Limited | Controlled release pharmaceutical dosage forms of trimetazidine |
| CN102824644A (en) * | 2012-09-13 | 2012-12-19 | 浙江诚意药业有限公司 | High-stability sustained-release tablet prepared by using hydroxy propyl cellulose |
| CN102885795A (en) * | 2012-10-31 | 2013-01-23 | 广州帝奇医药技术有限公司 | Trimetazidine dihydrochloride sustained-release tablet and preparation method thereof |
| CN104473905A (en) * | 2014-11-20 | 2015-04-01 | 美吉斯制药（厦门）有限公司 | Trimetazidine hydrochloride sustained-release capsule and preparation method thereof |
| CN105878200A (en) * | 2014-11-18 | 2016-08-24 | 郑州泰丰制药有限公司 | Trimetazidine hydrochloride sustained release tablets and preparation method thereof |
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2017
- 2017-12-12 CN CN201711313479.4A patent/CN109908096A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1108424A1 (en) * | 1999-12-17 | 2001-06-20 | Adir Et Compagnie | Matrix tablet for sustained release of trimetazidine after oral administration |
| CN1302663A (en) * | 1999-12-17 | 2001-07-11 | 阿迪尔公司 | Substrate tablet containing trimetazidine capable of long time controlled release after oral application |
| US20020006435A1 (en) * | 2000-01-27 | 2002-01-17 | Samuels Paul J. | Transdermal anesthetic and vasodilator composition and methods for topical administration |
| WO2009034541A9 (en) * | 2007-09-11 | 2009-12-30 | Ranbaxy Laboratories Limited | Controlled release pharmaceutical dosage forms of trimetazidine |
| CN102824644A (en) * | 2012-09-13 | 2012-12-19 | 浙江诚意药业有限公司 | High-stability sustained-release tablet prepared by using hydroxy propyl cellulose |
| CN102885795A (en) * | 2012-10-31 | 2013-01-23 | 广州帝奇医药技术有限公司 | Trimetazidine dihydrochloride sustained-release tablet and preparation method thereof |
| CN105878200A (en) * | 2014-11-18 | 2016-08-24 | 郑州泰丰制药有限公司 | Trimetazidine hydrochloride sustained release tablets and preparation method thereof |
| CN104473905A (en) * | 2014-11-20 | 2015-04-01 | 美吉斯制药（厦门）有限公司 | Trimetazidine hydrochloride sustained-release capsule and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110623934A (en) * | 2019-09-26 | 2019-12-31 | 杭州百诚医药科技股份有限公司 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
| CN112315942A (en) * | 2020-11-04 | 2021-02-05 | 南京康川济医药科技有限公司 | Trimetazidine hydrochloride sustained release preparation and preparation method thereof |
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Application publication date: 20190621 |
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