CN101773508B - Stable Trifusal pharmaceutical composition - Google Patents
Stable Trifusal pharmaceutical composition Download PDFInfo
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- CN101773508B CN101773508B CN2010191020143A CN201019102014A CN101773508B CN 101773508 B CN101773508 B CN 101773508B CN 2010191020143 A CN2010191020143 A CN 2010191020143A CN 201019102014 A CN201019102014 A CN 201019102014A CN 101773508 B CN101773508 B CN 101773508B
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- triflusal
- trifusal
- stable
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Abstract
The invention discloses a stable trifusal pharmaceutical composition, which is characterized by comprising trifusal, a surface active agent and other receivable carriers on the aspect of the pharmacy. 1000 grains of stable traifusal pharmaceutical composition comprise the following components: 100 to 600 g trifusal, 50 to 200 g lactose, 1 to 12g lauryl sodium sulfate, 1 to 10g magnesium stearate and 1 percent citric acid and 10 percent starch slurry with appropriate quantity. The invention also relates to a preparation method of trifusal capsule. The trifusal tablet which is prepared by the formula and the preparation method has good fluidity, good dissolution, small charge quantity difference, good stability, high biological utilization degree and good curative effect.
Description
Technical field
The present invention relates to a kind of triflusal medicament composition and preparation method thereof.
Background technology
Triflusal, a kind of novel antithrombotic, its chemical name is: 2-acetoxyl group-4-(Trifluoromethyl)benzoic acid..
Its structural formula is:
Molecular formula: C
10H
7F
3O
4
Molecular weight: 248.2
The sickness rate of thrombotic disease such as myocardial infarction and cerebral thrombosis, disability rate and mortality rate are all occupied the forefront in various diseases.Coronary artery or cerebrovascular stricture of artery and thrombosis are on atherosclerotic basis, due to blood vessel damages repeatedly.During blood vessel injury; Platelet adhesion is in the subendothelial tissue that exposes; Adherent platelet discharges content adenosine diphosphate (ADP) (ADP) and the platelet in the two activation circulation of thromboxane A2 (TXA2) that the membrane phospholipid metabolism forms in its granule; In fibrinogenic presence, the agglomerating formation platelet thrombus of platelet aggregation.Blood vessel injury also activates blood coagulation system, and the thrombin of generation impels platelet further to assemble, and also causes fibrinous formation, and is firm through the crosslinked arterial thrombus that makes.Antiplatelet drug can suppress hematoblastic adhesion, gathering and release function, prevents thrombosis, therefore in the control of thrombotic disease, has critical role.
Aspirin is a present clinical practice platelet suppressant drug the most widely; But the digestive tract ulcer that in application process, occurs, side effect such as hemorrhage to a great extent limit its use; Even reduce the generation that dosage can not be avoided above-mentioned side effect fully, there is bibliographical information to take the generation that aspirin 10mg still can significantly increase the scope lower gastrointestinal hemorrhage every day.The advantage of aspirin is irreversibly to suppress the platelet Cycloxygenase, thereby long term inhibition platelet function and platelet rely on the formation of TX.Its shortcoming is at finite concentration, has suppressed the form of ownership of Cycloxygenase indiscriminately, makes the generation of the intravital PGI2 of the atherosis patient of late arterial reduce.Because aspirin does not influence hematoblastic secretion and sticks when suppress forming, so it neither delays arteriosclerotic process, does not also suppress the division of VSMC.Aspirin does not have the obvious suppression effect for the platelet activation that other stimulations such as ADP produce yet.
The agent of trifluoro Salix anti-platelet aggregation has more special effect than aspirin (aspirin) on prevention and treatment thrombotic disease and complication.Compare with aspirin, the activity of antagonism cyclooxygenase and c-AMP phosphodiesterase simultaneously, the antiplatelet aggregation ability is strong, but very little to the biosynthetic influence of prostacyclin when therapeutic dose, danger of bleeding property is also very little.Research shows that triflusal and aspirin be indifference aspect prevention peripheral arteriosclerosis occlusive disease (PAOD) patient serious cardiovascular incident, but the incidence rate of its severe haemorrhage complication significantly is lower than the aspirin group.
Though aspirin is a kind of standard antiplatelet drug of clinical treatment acute ischemia syndrome, its bleeding complications, especially cerebrovascular is hemorrhage, remains doctors' misgivings.Result of study shows that triflusal is used for reaching 35 days after the acute myocardial infarction (AMI), and the generation that cerebrovascular is hemorrhage obviously reduces, always hemorrhage (each position) though minimizing do not reach statistical significance, the tool clinical meaning.Therefore, triflusal is the fabulous medicine of selecting for use a kind of AMI of confession acute stage, and hemorrhage high-risk maybe can not tolerate aspirin or patient hypersensitive are especially arranged.Two clinical experimental study results that are published in the 26th international apoplexy conference of AHA show that triflusal is effective equally with aspirin aspect prevention of recurrence type cerebral infarction, and bleeding complications is few.
CN200910000908.1 discloses a kind of triflusal medicament composition and preparation method thereof, and this solid composite medicament adopts conventional adjuvant and conventional method for preparing to make.
Since the triflusal unique physical and chemical properties,, specification is bigger, the dissolving difficulty, influence absorbs.
Therefore, seek effective way, improve the triflusal dissolubility, increase drug dissolution, it is extremely urgent with stability triflusal oral solid formulation preferably to prepare higher bioavailability.
Summary of the invention
According to existing adjuvant and working condition; Guaranteeing to have lower production cost and simple preparation technology; Be suitable under the prerequisite of large-scale industrial production; Be necessary to work out a kind of suitable prescription and form and preparation technology, make triflusal have good bioavailability and stability of drug products.
The present invention has prepared a kind of oral solid drug composition of stable triflusal, has solved the deficiency of present triflusal preparation effectively, has solved the hydrophobic problem of triflusal simultaneously through specific mode.The oral solid drug composition formulation and technology that obtains is simple, favorable reproducibility, and dissolution is high, good stability.
The invention provides a kind of stable triflusal medicament composition, it is characterized in that containing triflusal, surfactant and other pharmaceutically acceptable carrier.
The invention provides a kind of stable triflusal medicament composition, it is characterized in that its described surfactant is selected from a kind of or its mixture in sodium lauryl sulphate, dodecyl sodium sulfate, the octadecyl good fortune horse acid sodium.
The invention provides a kind of stable triflusal medicament composition, it is characterized in that its described surfactant is preferably from sodium lauryl sulphate.
Triflusal medicament composition of the present invention, compositions are capsule.
The invention provides a kind of triflusal medicament composition, the prescription that it is characterized in that processing 1000 is formed as follows:
The method for preparing of triflusal medicament composition of the present invention is characterized in that described method for preparing comprises the steps:
1) preparation of supplementary material and processing: triflusal was pulverized 100 mesh sieves, and it is subsequent use that other adjuvant is crossed 100 mesh sieves respectively.
2) weighing with mix: calculate inventory and take by weighing above-mentioned supplementary material respectively through double checking according to recipe quantity.With above-mentioned supplementary material mix homogeneously.
3) granulate: the system soft material is granulated with 20 order nylon screens with 1% citric acid, 10% starch slurry system soft material, and the granule that makes should lack fine powder, does not neatly have rectangular.
4) drying: 50 ℃ ± 5 ℃ dryings.
5) granulate: select 20 mesh sieve granulate for use.
6) total mixing: adding adds lubricant, mix homogeneously.
7) intermediate check.
8) fill:, regulate filling machine, fill according to the actual loading amount of result of calculation gained.
9) packing.
Below through conceptual design and prescription screening explanation the present invention.
The raw material physicochemical property
| Character | White or off-white color crystalline powder |
| Dissolubility | Water-soluble hardly, very easily be dissolved in ethanol |
| Hygroscopicity | 92.5% super-humid conditions held 10 days, weightening finish was less than 1%. |
| Bulk density | 0.35g/ml |
| Mobile | Extreme difference.(about 60 ° of angle of reposes) |
Stability: in influence factor's test of raw material; Raw material is placed in 60 ℃ of pyritous calorstats unstable; Put it at 40 ℃ of pyritous calorstats according to the medicine stability guideline; Raw material under 4500LX ± 500LX illumination condition, in 40 ℃ of pyritous calorstats and the calorstat of 25 ℃ of relative humiditys 92.5% ± 5% (KNO3 saturated solution) to place influence factor's result of the test of 10 days all up to specification, the research of prescription design and craft provides scientific basis.According to raw material unsettled character under hot conditions, we put into 40 ℃ of pyritous calorstats investigations in the prescription design and in screening with preparation.
Because these article specification is bigger, and the mobile extreme difference of raw material, so get rid of the direct fill of powder, select the wet granulation fill.
1. prescription design in advance
Be filler with starch in the prescription, 1% aqueous solution of citric acid is a binding agent, and water miscible sodium lauryl sulphate is a lubricant, manufactures experimently 100.
Triflusal 30g
Starch 10g
1% aqueous solution of citric acid is an amount of
Sodium lauryl sulphate 1g
Magnesium stearate 0.5g
Process 100
Preparation technology:
1. take by weighing the supplementary material of recipe quantity, cross 100 mesh sieves respectively, fully mixing.
2. water system soft material, 20 mesh sieves are granulated.
3. 50 ℃ of aeration-dryings, dried granule is crossed 20 mesh sieve granulate, mixes mix homogeneously outside adding.
Preparatory prescription trial result
Prescription screening
Be filler with starch, microcrystalline Cellulose, lactose respectively in the prescription, starch slurry is a binding agent, and sodium lauryl sulphate is a lubricant, has designed prescription 1-6, manufactures experimently 100.
Preparation technology is the same.
(1). ocular estimate
Investigate the grain forming of respectively writing out a prescription, and survey its angle of repose, investigate particulate flowability:
Prescription 1-6 trial result
Above experimental result shows, prescription 4, prescription 5, prescription 6 all are superior to writing out a prescription 1, prescription 2, prescription 3; Further investigate prescription 4, prescription 5, prescription 6.
(2). the capsule model is selected
Select prescription 4-6 to measure its bulk density, select suitable capsule number dress capsule
Prescription 4-6 capsule selection result
So select the 0# capsule charge.
(3). investigate disintegration
Each capsular disintegration of writing out a prescription is by " Chinese pharmacopoeia version appendix in 2005 XA inspection technique disintegration is measured.
(4). stripping curve is measured
Top mensuration result showed the stripping curve basically identical of respectively writing out a prescription, and all reached maximum stripping at 45 minutes.
(5). the balance water absorption is measured
Because moisture is very big to the influence of capsule end product quality,, select the minimum conduct of hygroscopicity finally to write out a prescription so measure the content wettability power of respectively writing out a prescription.Get prescription 4-6 content and place respectively under 75% ± 5% and 92.5 ± 5% super-humid conditions, in 1 day, 2 days, 4 days, 6 days, 10 natural gift another name weight.
Prescription 4-6 moisture absorption weightening finish (%)
Conclusion: particle appearance, flowability, disintegration and dissolution test show the almost indifference of respectively writing out a prescription, but the 6 moisture absorptions weightening finish of writing out a prescription is up to specification, tentatively confirm prescription, and the square gauge mould that Clicks here amplifies three batches, investigate each index.
We get first and further carry out the influence factor and test the investigation result of the test.
The specific embodiment
Below in conjunction with embodiment the present invention is done further explain, but should understand the non-scope that only limits to these embodiment of scope of the present invention.
Embodiment 1
Method for preparing comprises the steps:
1) preparation of supplementary material and processing: triflusal was pulverized 100 mesh sieves, and it is subsequent use that other adjuvant is crossed 100 mesh sieves respectively.
2) weighing with mix: calculate inventory and take by weighing above-mentioned supplementary material respectively through double checking according to recipe quantity.With above-mentioned supplementary material mix homogeneously.
3) granulate: the system soft material is granulated with 20 order nylon screens with 1% citric acid, 10% starch slurry system soft material, and the granule that makes should lack fine powder, does not neatly have rectangular.
4) drying: 50 ℃ ± 5 ℃ dryings.
5) granulate: select 20 mesh sieve granulate for use.
6) total mixing: adding adds lubricant, mix homogeneously.
7) intermediate check.
8) fill:, regulate filling machine, fill according to the actual loading amount of result of calculation gained.
9) packing.
Test Example 1
Product with the embodiment of the invention 1 compares stability test, and the result is following:
Table 1 constant temperature accelerated stability test result
The table 2 room temperature stability test result that keeps sample
Last table shows that the sample of the embodiment of the invention 1 is comparatively stable, and it is qualified that each index detects.
Claims (2)
1. the solid composite medicament of a stable triflusal, the prescription that it is characterized in that processing 1000 is formed as follows:
。
2. the method for preparing of the solid composite medicament of stable triflusal according to claim 1 is characterized in that described method for preparing comprises the steps:
1) preparation of supplementary material and processing: triflusal was pulverized 100 mesh sieves, and it is subsequent use that other adjuvant is crossed 100 mesh sieves respectively;
2) weighing with mix: calculate inventory and take by weighing above-mentioned supplementary material respectively through double checking according to recipe quantity, with above-mentioned supplementary material mix homogeneously;
3) granulate: the system soft material is granulated with 20 order nylon screens with 1% citric acid, 10% starch slurry system soft material, and the granule that makes should lack fine powder, does not neatly have rectangular;
4) drying: 50 ℃ ± 5 ℃ dryings;
5) granulate: select 20 mesh sieve granulate for use;
6) total mixing: adding adds lubricant, mix homogeneously;
7) intermediate check;
8) fill:, regulate filling machine, fill according to the actual loading amount of result of calculation gained;
9) packing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010191020143A CN101773508B (en) | 2010-02-08 | 2010-02-08 | Stable Trifusal pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010191020143A CN101773508B (en) | 2010-02-08 | 2010-02-08 | Stable Trifusal pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101773508A CN101773508A (en) | 2010-07-14 |
| CN101773508B true CN101773508B (en) | 2012-01-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010191020143A Expired - Fee Related CN101773508B (en) | 2010-02-08 | 2010-02-08 | Stable Trifusal pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101773508B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104367583B (en) * | 2014-11-20 | 2017-04-19 | 海南中玉药业有限公司 | Triflusal pharmaceutical composition with high bioavailability |
| CN115212206B (en) * | 2022-08-15 | 2023-04-18 | 江苏知原药业股份有限公司 | Medicinal composition containing pirfenidone and preparation method thereof |
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2010
- 2010-02-08 CN CN2010191020143A patent/CN101773508B/en not_active Expired - Fee Related
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| CN101773508A (en) | 2010-07-14 |
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