CN105457036A - Rivaroxaban pharmaceutical composition and preparation method thereof - Google Patents
Rivaroxaban pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN105457036A CN105457036A CN201410387341.9A CN201410387341A CN105457036A CN 105457036 A CN105457036 A CN 105457036A CN 201410387341 A CN201410387341 A CN 201410387341A CN 105457036 A CN105457036 A CN 105457036A
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- razaxaban
- pharmaceutical composition
- mannitol
- lactose
- magnesium stearate
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Abstract
The present invention discloses a rivaroxaban pharmaceutical composition, which contains rivaroxaban, mannitol, lactose, low-substituted hydroxypropyl cellulose and magnesium stearate, wherein a weight ratio of the rivaroxaban to the mannitol to the lactose is 1:5:10. The rivaroxaban pharmaceutical composition of the present invention has characteristics of good stability, product yield improving, cost reducing, industrialization achieving, good clinical application, effective dissolution improving, and significantly improved bioavailability.
Description
Technical field
The invention belongs to medical art, be specifically related to razaxaban pharmaceutical composition and preparation method thereof.
Background technology
Razaxaban
English name: Rivaroxaban;
The chloro-N-of chemical name: 5-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]-5-oxazolidinyl] methyl]-2-thenoyl amine;
Structural formula:
Molecular formula: C
19h
18clN
3o
5s;
Molecular weight: 435.88;
Indication: for preventing the formation of hip joint and knee prosthesis postoperative patient person deep venous thrombosis (DVT) and pulmonary infarction (PE).Also can be used for prevention non-valve artrial fibrillation patient's apoplexy and non-central nervous system's property thromboembolism, reduce the risk etc. of coronary syndrome recurrence.
Pharmacology type: razaxaban high selectivity and contestable suppress Xa factor that is free and that combine and prothrombin activity, extend activated partial thromboplastin time plate (APTT) and prothrombin time (PT) with dose-dependent fashion.
In existing patent 200480035106.X, the preparation technology of razaxaban tablet adopts adhesive and surfactant wiring solution-forming, filler and disintegrating agent mix, use fluid bed wet granulation after raw material micronization, lubricant are additional, and last tabletting, coating are made.201410113352.8 disclose razaxaban raw material micronization, the raw material after post processing and hydrophilicity condiment, disintegrating agent, surfactant mixed pelletization, and additional adjuvant, finally by mixture tabletting, tablet carries out coating.The razaxaban pharmaceutical composition that prior art is produced, requires high to production equipment, mostly adopts import equipment, costly, be not easy to this project of industrialized implementation.
The present inventor is through studying for a long period of time, and unexpected discovery, applies special adjuvant, razaxaban pharmaceutical composition prepared by special process, reliable in quality, dissolution rate is fast, not only successfully solves razaxaban and is not easy to Industrialization, and reduction production cost, easy to implement, remarkable in economical benefits.
Summary of the invention
The first object of the present invention is to provide a kind of razaxaban pharmaceutical composition, and this razaxaban pharmaceutical composition, to good stability, to raising product yield, reduces costs, realizes industrialization, be better applied to clinical, have more obvious advantage.
The second object of the present invention is the preparation method providing razaxaban pharmaceutical composition of the present invention, and the method is simple, and prepared razaxaban pharmaceutical composition, steady quality is reliable.
For realizing the first object of the present invention, the present inventor is surprised to find that a kind of pharmaceutical composition of razaxaban, containing razaxaban, mannitol, lactose, low-substituted hydroxypropyl cellulose, magnesium stearate, wherein razaxaban: mannitol: the weight ratio of lactose is 1:5:10.
The present invention adopts following technical scheme:
A razaxaban pharmaceutical composition particularly, the razaxaban pharmaceutical composition described in it, every 1000 slice prescriptions consist of:
Razaxaban 5-10g
Mannitol 25-50g
Lactose 50-100g
Low-substituted hydroxypropyl cellulose 70-140g
Magnesium stearate 2g
Coating materials 4g
Preferably, the razaxaban pharmaceutical composition described in every 1000, its formula consists of:
Razaxaban 5g
Mannitol 25g
Lactose 50g
Low-substituted hydroxypropyl cellulose 70g
Magnesium stearate 2g
Coating materials 4g
Razaxaban pharmaceutical composition of the present invention is adopted and is prepared with the following method:
1) prepare: by low-substituted hydroxypropyl cellulose, lactose, magnesium stearate under 80 DEG C of conditions dry 4 hours, for subsequent use;
2) by the mannitol of recipe quantity and razaxaban, put in container, after mix homogeneously, be ground to granularity at 80 ± 10um, for subsequent use;
3) by 2) low-substituted hydroxypropyl cellulose of item and recipe quantity, magnesium stearate mix homogeneously;
4) tabletting: regulate suitable stiff and sheet weight, carry out tabletting;
5) coating: the film coating agent of recipe quantity is mixed with 70% ethanol the solution that solid content is 10%, regulates coating pan rotating speed, inlet temperature, pressure, carries out coating;
6) pack: adopt aluminium-plastic bubble plate packing machine to pack;
7) put in storage.
Traditional razaxaban pharmaceutical composition, requires high to production equipment, and uniformity of dosage units diversity is large, and quality cannot ensure.
The present inventor through a large amount of experimental studies find, razaxaban pharmaceutical composition be above-mentioned formula and preparation technology time, described pharmaceutical composition uniformity of dosage units diversity is little, and quality is effectively ensured.
Compared with prior art, tool of the present invention has the following advantages:
1) new razaxaban compositions provided by the present invention thoroughly solves uniformity of dosage units in razaxaban production process and to differ greatly problem.
2) razaxaban pharmaceutical composition provided by the present invention is for the yield, the reduction production cost that improve this product, and being better applied to clinical treatment has very large help.
3) new razaxaban compositions provided by the present invention is through industrialized great production and study on the stability, and prove constant product quality, through pharmacology, toxicological test, solution is non-stimulated to blood vessel, without anaphylaxis, also without haemolysis, to human body fanout free region.
4) preparation method of new razaxaban compositions provided by the present invention, the method is simple, prepared razaxaban pharmaceutical composition reliable in quality.
5) new razaxaban compositions provided by the present invention, stripping is fast, and have higher bioavailability, reaching rapidly needs concentration.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail
embodiment 1
Razaxaban pharmaceutical composition described in every 1000, its formula consists of:
Razaxaban 5g
Mannitol 25g
Lactose 50g
Low-substituted hydroxypropyl cellulose 70g
Magnesium stearate 2g
Coating materials 4g
Preparation technology:
1) prepare: by low-substituted hydroxypropyl cellulose, lactose, magnesium stearate under 80 DEG C of conditions dry 4 hours, for subsequent use;
2) by the mannitol of recipe quantity and razaxaban, put in container, after mix homogeneously, be ground to granularity at 80 ± 10um, for subsequent use;
3) by 2) low-substituted hydroxypropyl cellulose of item and recipe quantity, magnesium stearate mix homogeneously;
4) tabletting: regulate suitable stiff and sheet weight, carry out tabletting;
5) coating: the film coating agent of recipe quantity is mixed with 70% ethanol the solution that solid content is 10%, regulates coating pan rotating speed, inlet temperature, pressure, carries out coating;
6) pack: adopt aluminium-plastic bubble plate packing machine to pack;
7) put in storage.
embodiment 2
Razaxaban pharmaceutical composition described in every 1000, its formula consists of:
Razaxaban 10g
Mannitol 50g
Lactose 100g
Low-substituted hydroxypropyl cellulose 140g
Magnesium stearate 2g
Coating materials 4g
Preparation technology: with embodiment 1.
test example 1
This test example is the stability investigating razaxaban compositions provided by the present invention.
The accelerated test of razaxaban pharmaceutical composition
Preparing three batches of razaxaban pharmaceutical compositions (lot number is respectively 1005001,1005002,1005003) according to the method for the embodiment of the present invention 1 visits auspicious appropriate according to the commercially available product of commercially available back and razaxaban, at 40 DEG C ± 2 DEG C, the condition of RH75% ± 5% places 6 months, period respectively at the 1st, sampling in 2,3,6 months, detect according to stability inspection item, and compare with 0 day data.
1, project is investigated
High spot reviews: character, related substance and content.
2, accelerated test result
Above conclusion (of pressure testing) can be found out: this product places 6 months every Testing index no significant difference compared with 0 month under accelerated test condition, and stability is better compared with commercially available product.
Test example 2
Adopt Chinese Pharmacopoeia 2010 editions annex XC dissolution method second method (paddle method) 75rpm.Using the Ph4.5 acetate buffer 900mL containing 0.2%SDS as dissolution medium, detect the embodiment of the present invention 1, the tablet of embodiment 2 preparation and the stripping curve of commercially available product, result is as follows:
| Sample the time | 5min | 15min | 30min | 45min | 60min |
| Embodiment 1 | 87 | 95 | 98 | 99 | 100 |
| Embodiment 2 | 86 | 93 | 96 | 99 | 100 |
| Commercially available product | 82 | 89 | 92 | 94 | 98 |
Testing result illustrates, the sample adopting method of the present invention to prepare, has dissolution rate fast.
Claims (5)
1. a razaxaban pharmaceutical composition, containing razaxaban, mannitol, lactose, low-substituted hydroxypropyl cellulose, magnesium stearate, is characterized in that razaxaban: mannitol: the weight ratio of lactose is 1:5:10.
2. razaxaban pharmaceutical composition according to claim 1, is characterized in that, the razaxaban pharmaceutical composition described in it, and every 1000 its formula consist of:
Razaxaban 5-10g
Mannitol 25-50g
Lactose 50-100g
Low-substituted hydroxypropyl cellulose 70-140g
Magnesium stearate 2g
Coating materials 4g.
3. razaxaban pharmaceutical composition according to claim 2, is characterized in that, the razaxaban pharmaceutical composition described in it, and every 1000 its formula consist of:
Razaxaban 5g
Mannitol 25g
Lactose 50g
Low-substituted hydroxypropyl cellulose 70g
Magnesium stearate 2g
Coating materials 4g.
4. razaxaban pharmaceutical composition according to claim 2, is characterized in that, the razaxaban pharmaceutical composition described in it, and every 1000 its formula consist of:
Razaxaban 10g
Mannitol 50g
Lactose 100g
Low-substituted hydroxypropyl cellulose 140g
Magnesium stearate 2g
Coating materials 4g.
5. the preparation method of razaxaban pharmaceutical composition according to claim 1, it is characterized in that, the method comprises the steps:
1)prepare: by low-substituted hydroxypropyl cellulose, lactose, magnesium stearate under 80 DEG C of conditions dry 4 hours, for subsequent use;
2)by the mannitol of recipe quantity and razaxaban, put in container, after mix homogeneously, be ground to granularity at 80 ± 10um, for subsequent use;
3)by 2) low-substituted hydroxypropyl cellulose of item and recipe quantity, magnesium stearate mix homogeneously;
4)tabletting: regulate suitable stiff and sheet weight, carry out tabletting;
5)coating: the film coating agent of recipe quantity is mixed with 70% ethanol the solution that solid content is 10%, regulates coating pan rotating speed, inlet temperature, pressure, carries out coating;
6)packaging: adopt aluminium-plastic bubble plate packing machine to pack;
7)warehouse-in.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410387341.9A CN105457036A (en) | 2014-08-08 | 2014-08-08 | Rivaroxaban pharmaceutical composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410387341.9A CN105457036A (en) | 2014-08-08 | 2014-08-08 | Rivaroxaban pharmaceutical composition and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105457036A true CN105457036A (en) | 2016-04-06 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410387341.9A Pending CN105457036A (en) | 2014-08-08 | 2014-08-08 | Rivaroxaban pharmaceutical composition and preparation method thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN105457036A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022140430A (en) * | 2021-03-10 | 2022-09-26 | 日本ジェネリック株式会社 | Rivaroxaban-containing tablet |
-
2014
- 2014-08-08 CN CN201410387341.9A patent/CN105457036A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022140430A (en) * | 2021-03-10 | 2022-09-26 | 日本ジェネリック株式会社 | Rivaroxaban-containing tablet |
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| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160406 |
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| WD01 | Invention patent application deemed withdrawn after publication |