CN105878200A - Trimetazidine hydrochloride sustained release tablets and preparation method thereof - Google Patents
Trimetazidine hydrochloride sustained release tablets and preparation method thereof Download PDFInfo
- Publication number
- CN105878200A CN105878200A CN201410654544.XA CN201410654544A CN105878200A CN 105878200 A CN105878200 A CN 105878200A CN 201410654544 A CN201410654544 A CN 201410654544A CN 105878200 A CN105878200 A CN 105878200A
- Authority
- CN
- China
- Prior art keywords
- release tablets
- trimetazidine hydrochloride
- hydrochloride sustained
- hypromellose
- sustained release
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- UHWVSEOVJBQKBE-UHFFFAOYSA-N Trimetazidine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCNCC1 UHWVSEOVJBQKBE-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229960001177 trimetazidine Drugs 0.000 title claims abstract description 34
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000003826 tablet Substances 0.000 claims abstract description 12
- 239000000314 lubricant Substances 0.000 claims abstract 3
- 238000013268 sustained release Methods 0.000 claims abstract 3
- 239000012730 sustained-release form Substances 0.000 claims abstract 3
- 239000000945 filler Substances 0.000 claims abstract 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 12
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 12
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 12
- 229960003943 hypromellose Drugs 0.000 claims description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 239000007779 soft material Substances 0.000 claims description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims 2
- 239000000377 silicon dioxide Substances 0.000 claims 2
- 235000012239 silicon dioxide Nutrition 0.000 claims 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 238000005469 granulation Methods 0.000 claims 1
- 230000003179 granulation Effects 0.000 claims 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 1
- 239000008108 microcrystalline cellulose Substances 0.000 claims 1
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract 1
- 235000021152 breakfast Nutrition 0.000 abstract 1
- 230000003111 delayed effect Effects 0.000 abstract 1
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- 206010052895 Coronary artery insufficiency Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 208000026758 coronary atherosclerosis Diseases 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of medicinal preparations, and in particular to trimetazidine hydrochloride sustained release tablets and a preparation method of the trimetazidine hydrochloride sustained release tablets. The trimetazidine hydrochloride sustained release tablets adopt hydrophilic gel as a sustained release framework material, and also contain a filling agent, a lubricating agent and other auxiliary materials. The prepared trimetazidine hydrochloride sustained release tablets are taken twice each day, 1 tablet each time, and the two rimetazidine hydrochloride sustained release tablets are taken at the breakfast time and the supper time respectively. Therefore, the trimetazidine hydrochloride sustained release tablets have the advantages that the drug can be slowly and uniformly released, thus the release rate is reduced, the peak time is delayed, the taking times each day is reduced, and the medicine-taking compliance of a patient is improved. In addition, the preparation method is simple in technology and easy to operate.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof.
Background technology
Trimetazidine (Trimetazidine) chemical name is 1-(2,3,4-trimethoxy benzyl) piperazine, and it can suppress fatty acid (FFA) to aoxidize,
Stimulate glucose oxidation, and antagonism Ischemic Myocardial Cells has protective effect to a certain extent.Trimetazidine Hydrochloride is widely used in the heart in recent years
The prophylactic treatment of angor outbreak and the complementary symptomatic treatment of vertigo and tinnitus.Angina pectoris is type relatively conventional in ischemic heart desease.Be due to
Coronary atherosclerosis, narrow, cause coronary insufficiency, caused by cardiac muscle ischemia and anoxia, be main with precordialgia
One group of syndrome of clinical manifestation, is the one of the coronary heart disease that incidence rate is the highest, and the Health and Living of the mankind in serious threat.Therefore, active development
The medicine controlling stable angina pectoris is the most necessary.
Trimetazidine tablets water solublity is relatively strong, 10 minutes stripping quantities more than 90%, and absorbed following oral administration is rapid, and the plasma peaks time is 1.5 hours, needs many
Secondary repetitively administered gets to steady plasma-drug concentration, and clinic need to be administered three times a day, each 20 to 40mg, and patient dependence is poor, it is difficult to dimension
Hold stable blood drug level.In order to control the rate of release of trimetazidine medicine, the coating material of various slow release continues on and updates, commonly using at present
Mainly have polyvinyl acetate and polypropylene ethyl ester-methylmethacrylate copolymer two kinds.After the trimetazidine tablets oral administration of both coatings,
Trimetazidine absorbs rapidly, i.e. reaches plasma peaks less than 2h, and the elimination half-life is about 6h, at least takes every day three times, and internal blood medicine is dense
Degree is easy to " peak valley " phenomenon occur, not only makes effective blood drug concentration hold time short, and side effect is big, and drug effect can not steadily play
In order to overcome the deficiencies in the prior art, it is an object of the invention to provide a kind of trimetazidine hydrochloride sustained-release tablets.
Summary of the invention
Another object of the present invention is to provide the preparation method of a kind of trimetazidine hydrochloride sustained-release tablets.
For achieving the above object, the technical solution adopted in the present invention is as follows:
By weight percentage, to account for tablet total weight amount as follows for each component:
A kind of method of trimetazidine hydrochloride sustained-release tablets, it is characterised in that comprise the following steps:
(1) mixing: Trimetazidine Hydrochloride, calcium hydrogen phosphate, hypromellose (K4M), hypromellose (K100M), stearic acid are pressed
It is uniformly mixed in batch mixer according to formula ratio；
(2) soft material processed: add in above-mentioned mixed component and be dissolved with the ethanol water mix homogeneously of polyvidone and make soft material, in comminutor
Pelletize with 16 mesh sieves, obtain soft powder；
(3) it is dried: above-mentioned soft powder is placed in drying baker and is dried；
(4) tabletting: above-mentioned dried powder and additional hypromellose (K100M), hypromellose (K4M), magnesium stearate, two
Silicon oxide uniformly mixes, and tabletting i.e. obtains slow releasing tablet.
In batch mixing step of the present invention, the time of stirring is 10-20 minute.
Detailed description of the invention
Embodiment 1
Following formula, is prepared as described above method, makes 4000 trimetazidine hydrochloride sustained-release tablets, and every finally given slow release tablet weighs about 200mg:
Embodiment 2
Following formula, is prepared as described above method, makes 4000 trimetazidine hydrochloride sustained-release tablets, and every finally given slow release tablet weighs about 200mg:
Use the device in 2010 editions second annex XC dissolution method of Chinese Pharmacopoeia, according to the assay method of annex XD release, respectively
Slow release tablet in Example 1-2 is each a piece of, and with water 500ml as dissolution medium, rotating speed is 75 turns/min, operates according to the method described above, point
Do not take corresponding solution when 1,2,3,4,8, filter, accurately pipette 5ml filtrate in 10ml volumetric flask with liquid-transfering gun, use 0.1mol/L
Sulfuric acid solution be diluted to scale, shake up, by ultraviolet visible spectrophotometry measure 232nm place absorbance, calculating burst size.
Above-described embodiment is only the preferred embodiment of the present invention, it is impossible to limit protection scope of the present invention with this, and those skilled in the art is at this
Change and the replacement of any unsubstantiality made on the basis of invention belong to scope of the present invention.
Claims (10)
1. a trimetazidine hydrochloride sustained-release tablets, it is characterised in that: use hydrophilic gel as sustained-release matrix material；
Described hydrophilic gel refers to the mixture of hypromellose (K4M) and hypromellose (K100M).
Trimetazidine hydrochloride sustained-release tablets the most according to claim 1, it is characterised in that: possibly together with filler or lubricant or other adjuvants or its mixture in described trimetazidine hydrochloride sustained-release tablets.
Trimetazidine hydrochloride sustained-release tablets the most according to claim 1 and 2, it is characterised in that: by weight percentage, it is as follows that each component accounts for tablet total weight amount:
。
Trimetazidine hydrochloride sustained-release tablets the most according to claim 3, it is characterised in that: described Trimetazidine Hydrochloride accounts for the 16%-23% of tablet total weight amount.
Trimetazidine hydrochloride sustained-release tablets the most according to claim 3, it is characterised in that: described hydrophilic gel sustained-release matrix material accounts for the 33%-53% of tablet total weight amount.
Trimetazidine hydrochloride sustained-release tablets the most according to claim 3, it is characterised in that: described hypromellose (K4M) is 1-10:1 with the weight ratio of hypromellose (K100M).
Trimetazidine hydrochloride sustained-release tablets the most according to claim 3, it is characterised in that: described fill one or both in calcium hydrogen phosphate, microcrystalline Cellulose of mixture；Described binding agent is selected from polyvidone, and described fluidizer is silicon dioxide；Described lubricant is magnesium stearate.
8. the method preparing the arbitrary described trimetazidine hydrochloride sustained-release tablets of claim 1-7, it is characterised in that comprise the following steps:
(1), mixing: Trimetazidine Hydrochloride, calcium hydrogen phosphate, hypromellose (K4M), hypromellose (K100M), stearic acid are uniformly mixed in batch mixer according to formula ratio；
(2) soft material processed: add in above-mentioned mixed component and be dissolved with the ethanol water mix homogeneously of polyvidone and make soft material, with 16 mesh sieves granulations in comminutor, obtain soft powder；
(3) it is dried: above-mentioned soft powder is placed in drying baker and is dried；
(4) tabletting: above-mentioned dried powder uniformly mixes with additional hypromellose (K100M), hypromellose (K4M), magnesium stearate, silicon dioxide, and tabletting i.e. obtains slow releasing tablet.
The preparation method of trimetazidine hydrochloride sustained-release tablets the most according to claim 8, it is characterised in that: in described batch mixing step, the time of stirring is 10-20 minute.
The preparation method of trimetazidine hydrochloride sustained-release tablets the most according to claim 8, it is characterised in that: in described drying steps, the temperature being dried is 50～70 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410654544.XA CN105878200A (en) | 2014-11-18 | 2014-11-18 | Trimetazidine hydrochloride sustained release tablets and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410654544.XA CN105878200A (en) | 2014-11-18 | 2014-11-18 | Trimetazidine hydrochloride sustained release tablets and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105878200A true CN105878200A (en) | 2016-08-24 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410654544.XA Pending CN105878200A (en) | 2014-11-18 | 2014-11-18 | Trimetazidine hydrochloride sustained release tablets and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105878200A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109908096A (en) * | 2017-12-12 | 2019-06-21 | 武汉武药科技有限公司 | A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof |
| 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 |
| CN116983272A (en) * | 2023-09-08 | 2023-11-03 | 江苏诺和必拓新药研发有限公司 | Ivabradine hydrochloride sustained release tablet and preparation method thereof |
-
2014
- 2014-11-18 CN CN201410654544.XA patent/CN105878200A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109908096A (en) * | 2017-12-12 | 2019-06-21 | 武汉武药科技有限公司 | A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof |
| 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 |
| CN116983272A (en) * | 2023-09-08 | 2023-11-03 | 江苏诺和必拓新药研发有限公司 | Ivabradine hydrochloride sustained release tablet and preparation method thereof |
| CN116983272B (en) * | 2023-09-08 | 2024-05-31 | 江苏诺和必拓新药研发有限公司 | Ivabradine hydrochloride sustained release tablet and preparation method thereof |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160824 |