CN102319225B - Trimetazidine hydrochloride sustained release tablet and preparation method thereof - Google Patents
Trimetazidine hydrochloride sustained release tablet and preparation method thereof Download PDFInfo
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- CN102319225B CN102319225B CN 201110286002 CN201110286002A CN102319225B CN 102319225 B CN102319225 B CN 102319225B CN 201110286002 CN201110286002 CN 201110286002 CN 201110286002 A CN201110286002 A CN 201110286002A CN 102319225 B CN102319225 B CN 102319225B
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- trimetazidine hydrochloride
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- release tablet
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Abstract
The invention belongs to the field of sustained release medicament preparations, and particularly relates to a trimetazidine hydrochloride sustained release tablet and a preparation method thereof. The trimetazidine hydrochloride sustained release tablet is prepared from 40 to 45 parts of trimetazidine hydrochloride, 100 to 200 parts of polyoxyethylene, 100 to 200 parts of dextrin, 60 to 100 parts of 3-10 percent ethyl cellulose solution and 3 to 5 parts of magnesium stearate through material mixing, soft material preparing, drying, tabletting and other steps. In the trimetazidine hydrochloride sustained release tablet, the polyoxyethylene serves as an auxiliary material, and the sustained release tablet is prepared from the medicaments by a method of direct tabletting or tabletting aftergranulating. The drug dissolution of the trimetazidine hydrochloride sustained release tablet reaches about 90 percent 6 hours later, so the sustained release tablet is only required to be taken twice a day; therefore, the sustained release tablet has the advantages of releasing drug slowly and uniformly to reduce release rate and postpone peak time, reducing the number of administration times per day, improving the compliance of patients to the medicament and the like. Furthermore, the preparation method of the invention is simple and easy to operate.
Description
Technical field
The invention belongs to the sustained release pharmaceutical formulation field, be specifically related to a kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof.
Background technology
Angina pectoris is type comparatively common in the ischemic heart desease.It is reported that the U.S. has 7,200,000 people to suffer from angina pectoris approximately, and with annual 350000 people's speed increase, therefore sick and dead number accounts for 1/3～1/2 of human mortality's sum up to more than 50 ten thousand people, accounts for 50～75% of deaths from heart disease sum.In China, along with the raising of living standards of the people, the change of life style and the quickening of rhythm of life, anginal sickness rate increases year by year.Take Beijing that sickness rate ranks first in the country as example, the case fatality rate that angina pectoris in 2003 is associated with complication accounts for 13% of human mortality's sum, and is still in rising trend at present, near American-European countries's level.Therefore, the medicine of active development control stable angina pectoris is very necessary.
The trimetazidine chemical name is 1-(2,3,4-trimethoxy benzyl) piperazine.Trimetazidine can with the hydrochloric acid salify, its dihydrochloride is widely used in clinically at home and abroad at present, is mainly used in the prophylactic treatment of angina pectoris attacks, and dizzy and complementary symptomatic treatment tinnitus.Trimetazidine belongs to other class antianginal cardiovascular drugses; trimetazidine is by the energy metabolism of Cell protection under anoxia and ischemia; stop the decline of ATP level in the cell; thereby guaranteed the normal operation of normal function and the permeable membrane sodium-potassium stream of ionic pump, kept the stable of intracellular environment.
The control experiment of patient with angina pectoris shows: trimetazidine can increase Coronary Blood Flow Reserve, rises in the 15th day at begin treatment, and lag motion brings out the generation of ischemia; Trimetazidine can limit stirring fast of blood pressure and not obviously change of heart rate; Trimetazidine can obviously reduce the frequency of angina pectoris attacks; It can also obviously reduce the use of glyceryl trinitrate.
Trimetazidine sheet water solublity is stronger, stripping quantity was more than 90% in 10 minutes, oral rear absorption is rapid, the plasma peaks time is 1.5 hours, need repeatedly repetitively administered could arrive steady plasma-drug concentration, clinical need administration every day 3 times, and each 20 to 40mg, patient dependence is relatively poor, is difficult to keep stably blood drug level.In order to control the rate of release of trimetazidine medicine, the coating material of various slow release constantly uses and upgrades, at present two kinds of polyvinyl acetate and the polypropylene ethyl ester-methylmethacrylate copolymers that mainly contain commonly used.After the trimetazidine sheet oral administration of these two kinds of coatings, trimetazidine absorbs rapidly, namely reach plasma peaks less than 2h, the elimination half-life is approximately 6h, at least take every day three times, the blood drug level in the body is easy to " peak valley " phenomenon occur, not only makes the effective blood drug concentration weak point of holding time, and side effect is large, and drug effect can not steadily be brought into play.
Summary of the invention
In order to overcome the deficiencies in the prior art, the object of the present invention is to provide a kind of trimetazidine hydrochloride sustained-release tablets.
Another object of the present invention is to provide a kind of preparation method of trimetazidine hydrochloride sustained-release tablets.
For achieving the above object, the technical solution adopted in the present invention is as follows:
A kind of trimetazidine hydrochloride sustained-release tablets, its prescription is composed as follows:
Trimetazidine Hydrochloride 40-45 part
100～200 parts of polyoxyethylene
100～200 parts in dextrin
60～100 parts of 3-10% ethyl cellulose liquid
Magnesium stearate 3-5 part.
Because the size of polyoxyethylene (PEO) molecular weight is on the impact of release dynamics, the PEO that relative molecular weight is higher is the good adjuvant of slow controlling agent, and therefore, the PEO relative molecular mass that adopts among the present invention is 4 * 10
6～6 * 10
6
A kind of preparation method of trimetazidine hydrochloride sustained-release tablets, it may further comprise the steps:
(1) batch mixing: Trimetazidine Hydrochloride and polyoxyethylene, dextrin are mixed in batch mixer according to formula ratio;
(2) soft material processed: add ethyl cellulose liquid mix homogeneously in the above-mentioned mixed component and make soft material, in comminutor, granulate with 16 mesh sieves, obtain soft powder;
(3) drying: above-mentioned soft powder places drying baker dry;
(4) tabletting: powder is evenly mixed with magnesium stearate after the above-mentioned drying, and tabletting namely gets slow releasing tablet.
In the batch mixing step of the present invention, the time of stirring is 15～20 minutes.
For polyoxyethylene is fully disperseed, in the preferred scheme, in the batch mixing step, add while stirring polyoxyethylene.
In the drying steps of the present invention, dry temperature is 60～70 ℃, and the water content that is dried to material is the 2-3%(mass percent).
In the preparation method of the present invention, may have a small amount of powder in the dry run of soft powder scatters, for this part powder of scattering can be taken full advantage of, the preparation method of trimetazidine hydrochloride sustained-release tablets of the present invention also is included in afterwards tabletting step again granulation step before of drying steps, is about to dried powder again by 16 mesh sieve granulate.
Every heavily about 170ml of trimetazidine hydrochloride sustained-release tablets of the present invention takes 2 every day, and each 1～2, full wafer is not chewed, and warm water takes and gets final product.
Compared to existing technology, beneficial effect of the present invention is: it is adjuvant that trimetazidine hydrochloride sustained-release tablets of the present invention adopts polyoxyethylene, method by direct compression or the rear tabletting of granulating, medicine is made slow releasing tablet, trimetazidine hydrochloride sustained-release tablets of the present invention after 6 hours the drug-eluting amount just reach about 90%, only need to take in one day and to get final product for twice; Therefore, the medicine of trimetazidine hydrochloride sustained-release tablets of the present invention can slowly discharge uniformly, reaches the reduction rate of release, postpones peak time, reduces medicining times every day, improves patient to the compliance of medicine; In addition, preparation method technique of the present invention is simple, easy to operate.
Below in conjunction with the specific embodiment the present invention is described in further detail.
The specific embodiment
A kind of preparation method of trimetazidine hydrochloride sustained-release tablets, it may further comprise the steps:
(1) batch mixing: Trimetazidine Hydrochloride and polyoxyethylene, dextrin are mixed in batch mixer according to formula ratio;
(2) soft material processed: add ethyl cellulose liquid mix homogeneously in the above-mentioned mixed component and make soft material, in comminutor, granulate with 16 mesh sieves, obtain soft powder;
(3) drying: above-mentioned soft powder places drying baker dry;
(4) tabletting: powder is evenly mixed with magnesium stearate after the above-mentioned drying, and tabletting namely gets slow releasing tablet.
Embodiment 1
Following prescription, by above-mentioned preparation method, make 2000 trimetazidine hydrochloride sustained-release tablets, the heavily about 170mg of every of finally obtaining slow release tablet:
Trimetazidine Hydrochloride 40g
Polyoxyethylene 100g
Dextrin 200g
3% ethyl cellulose liquid 60g
Magnesium stearate 3g.
Embodiment 2
Following prescription, by above-mentioned preparation method, make 2000 trimetazidine hydrochloride sustained-release tablets, the heavily about 170mg of every of finally obtaining slow release tablet:
Trimetazidine Hydrochloride 40g
Polyoxyethylene 150g
Dextrin 150g
5% ethyl cellulose liquid 80g
Magnesium stearate 3g.
Embodiment 3
Following prescription by above-mentioned preparation method, is made 2000 trimetazidine hydrochloride sustained-release tablets, final every heavily about 170mg of slow release tablet:
Trimetazidine Hydrochloride 45g
Polyoxyethylene 200g
Dextrin 100g
10% ethyl cellulose liquid 100g
Magnesium stearate 5g.
The experiment of drug-eluting amount:
Adopt the device in 2010 editions second appendix X C of the Chinese Pharmacopoeia dissolution method, assay method according to appendix X D release, get respectively each a slice of slow release tablet among the embodiment 1-2, take water 500ml as dissolution medium, rotating speed is 75 to turn/min, according to the method described above operation, got respectively corresponding solution at 1,2,3,4,5,6 o'clock, filter, accurately pipette 5ml filtrate in the 10ml volumetric flask with liquid-transfering gun, be diluted to scale with the sulfuric acid solution of 0.1mol/L, shake up, by the absorbance at ultraviolet visible spectrophotometry mensuration 232nm place, again according to C
14H
22N
2O
3The absorptance of 2HCl calculates burst size, the results are shown in Table 1.
Table 1: embodiment 1-2 trimetazidine hydrochloride sustained-release tablets burst size in time
Above-described embodiment only is preferred implementation of the present invention, can not limit protection scope of the present invention with this, and the variation of any unsubstantiality that those skilled in the art does on basis of the present invention and replacement all belong to the present invention's scope required for protection.
Claims (6)
1. trimetazidine hydrochloride sustained-release tablets is characterized in that: its prescription form and weight portion as follows:
Trimetazidine Hydrochloride 40-45 part
100～200 parts of polyoxyethylene
100～200 parts in dextrin
60～100 parts of 3-10% ethyl cellulose liquid
Magnesium stearate 3-5 part;
Described polyoxyethylated relative molecular mass is 4 * 10
6～6 * 10
6
2. the preparation method of trimetazidine hydrochloride sustained-release tablets as claimed in claim 1, it is characterized in that: it may further comprise the steps:
(1) batch mixing: Trimetazidine Hydrochloride and polyoxyethylene, dextrin are mixed in batch mixer according to formula ratio;
(2) soft material processed: add ethyl cellulose liquid mix homogeneously in the above-mentioned mixed component and make soft material, in comminutor, granulate with 16 mesh sieves, obtain soft powder;
(3) drying: above-mentioned soft powder places drying baker dry;
(4) tabletting: powder is evenly mixed with magnesium stearate after the above-mentioned drying, and tabletting namely gets slow releasing tablet.
3. the preparation method of trimetazidine hydrochloride sustained-release tablets according to claim 2, it is characterized in that: in the described batch mixing step, the time of stirring is 15～20 minutes.
4. it is characterized in that: in the described batch mixing step, add while stirring polyoxyethylene according to claim 2 or the preparation method of 3 described trimetazidine hydrochloride sustained-release tablets.
5. according to claim 3 or the preparation method of 4 described trimetazidine hydrochloride sustained-release tablets, it is characterized in that: in the described drying steps, dry temperature is 60～70 ℃, and the water content that is dried to material is 2～3%.
6. the preparation method of trimetazidine hydrochloride sustained-release tablets according to claim 5 is characterized in that: it also is included in the again granulation step before the tabletting step after the drying steps, is about to dried powder again by 16 mesh sieve granulate.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201110286002 CN102319225B (en) | 2011-09-23 | 2011-09-23 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
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| CN 201110286002 CN102319225B (en) | 2011-09-23 | 2011-09-23 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
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Families Citing this family (4)
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| 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 |
| CN104274419A (en) * | 2013-07-10 | 2015-01-14 | 广东省中药研究所 | Trimetazidine hydrochloride sustained release tablet taking glyceryl behenate as framework material and preparation method of trimetazidine hydrochloride sustained release tablet |
| CN108721235B (en) * | 2017-04-18 | 2021-07-02 | 江苏恒瑞医药股份有限公司 | Solid pharmaceutical composition containing trimetazidine or salt thereof and preparation method thereof |
| CN111888476A (en) * | 2020-08-17 | 2020-11-06 | 深圳市道科思医药有限公司 | Modified release pharmaceutical composition of trimetazidine dihydrochloride |
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| FR2717687B1 (en) * | 1994-03-24 | 1996-06-14 | Adir | Pharmaceutical compositions for the sustained release of trimetazidine after oral administration. |
| CN101455668A (en) * | 2007-12-14 | 2009-06-17 | 北京琥珀光华医药科技开发有限公司 | Preparation of trimetazidine hydrochloride sustained-release tablets and use thereof |
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