CN112107554A - Betricitaban capsule and preparation method thereof - Google Patents
Betricitaban capsule and preparation method thereof Download PDFInfo
- Publication number
- CN112107554A CN112107554A CN201910530251.3A CN201910530251A CN112107554A CN 112107554 A CN112107554 A CN 112107554A CN 201910530251 A CN201910530251 A CN 201910530251A CN 112107554 A CN112107554 A CN 112107554A
- Authority
- CN
- China
- Prior art keywords
- betrixaban
- capsule
- filler
- raw
- preparing
- 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.)
- Pending
Links
- 239000002775 capsule Substances 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 229950011103 betrixaban Drugs 0.000 claims abstract description 21
- XHOLNRLADUSQLD-UHFFFAOYSA-N betrixaban Chemical compound C=1C=C(Cl)C=NC=1NC(=O)C1=CC(OC)=CC=C1NC(=O)C1=CC=C(C(=N)N(C)C)C=C1 XHOLNRLADUSQLD-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 16
- 229940079593 drug Drugs 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 9
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 5
- 239000000314 lubricant Substances 0.000 claims abstract description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 13
- 229960001031 glucose Drugs 0.000 claims description 13
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 9
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 9
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 9
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 238000005303 weighing Methods 0.000 claims description 6
- 238000005550 wet granulation Methods 0.000 claims description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 229960001021 lactose monohydrate Drugs 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 239000007884 disintegrant Substances 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 229960001855 mannitol Drugs 0.000 claims description 3
- 229940083542 sodium Drugs 0.000 claims description 3
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 235000015424 sodium Nutrition 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 4
- 238000000643 oven drying Methods 0.000 claims 1
- 238000004806 packaging method and process Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000008213 purified water Substances 0.000 claims 1
- 239000007921 spray Substances 0.000 claims 1
- 239000000454 talc Substances 0.000 claims 1
- 229910052623 talc Inorganic materials 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 239000000080 wetting agent Substances 0.000 claims 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 6
- 206010014522 Embolism venous Diseases 0.000 description 3
- 208000004043 venous thromboembolism Diseases 0.000 description 3
- QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 description 1
- 229940123688 Direct Factor Xa inhibitor Drugs 0.000 description 1
- HGVDHZBSSITLCT-JLJPHGGASA-N Edoxaban Chemical compound N([C@H]1CC[C@@H](C[C@H]1NC(=O)C=1SC=2CN(C)CCC=2N=1)C(=O)N(C)C)C(=O)C(=O)NC1=CC=C(Cl)C=N1 HGVDHZBSSITLCT-JLJPHGGASA-N 0.000 description 1
- 229940123583 Factor Xa inhibitor Drugs 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960003886 apixaban Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960000622 edoxaban Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 229940100691 oral capsule Drugs 0.000 description 1
- 229960001148 rivaroxaban Drugs 0.000 description 1
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a betrixaban capsule and a preparation method thereof. The weight ratio of each component is as follows: 30-35 parts of betrixaban, 40-55 parts of a filling agent, 20-35 parts of a disintegrating agent and 1-2 parts of a lubricating agent. The prepared capsule has the advantages of simple preparation process, good stability, few auxiliary materials and the like.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a betrixaban capsule and a preparation method thereof.
Background
Betrixaban is currently used at home and abroad to prevent Venous Thromboembolism (VTE) in hospitalized patients with acute medical conditions at risk for thromboembolic complications due to moderate or severe limitation of activity and other VTE risk factors. Betrixaban (Betrixaban) is a once daily oral factor Xa inhibitor and is the 4 th direct factor Xa inhibitor anticoagulant marketed globally after rivaroxaban, apixaban, edoxaban. The dosage form on the market is an oral capsule, and has two specifications of 40 and 80 mg.
Disclosure of Invention
The application relates to the field of medicines, in particular to a betrixaban capsule, which is prepared by weighing a certain amount of raw material medicines and partially premixing the raw material medicines with a filling agent, uniformly mixing the premix with other auxiliary materials, carrying out wet granulation, drying and filling.
The betrixaban capsule comprises the following components in parts by weight:
| betriciban | 30 ~ 35 |
| Filler | 40 ~ 55 |
| Disintegrating agent | 20 ~ 35 |
| Lubricant agent | 1~2 |
The further betrixaban capsule has the filler selected from one or more of microcrystalline cellulose, spray-dried mannitol, glucose monohydrate, and lactose monohydrate.
The disintegrating agent of the betrixaban capsule is one or more of low-substituted hydroxypropyl cellulose, croscarmellose sodium and sodium carboxymethyl starch.
The disintegrant of the betrixaban capsule is one or more of croscarmellose sodium and sodium carboxymethyl starch.
Detailed Description
For a better understanding of the present invention, the present invention and advantages and benefits thereof will be described and illustrated in detail below by way of examples and experimental data of the present invention, which are not intended to limit the present invention.
Example 1:
| betriciban | 30 |
| Microcrystalline cellulose | 15 |
| Glucose monohydrate | 35 |
| Sodium carboxymethyl starch | 18 |
| Talcum powder | 2 |
The preparation process comprises the following steps: weighing the bulk drugs, microcrystalline cellulose, glucose monohydrate and sodium carboxymethyl starch according to the prescription amount, premixing the bulk drugs with the microcrystalline cellulose, uniformly mixing the premix with other auxiliary materials, performing wet granulation, and drying. Adding pulvis Talci, and encapsulating.
Example 2:
| betriciban | 35 |
| Glucose monohydrate | 45 |
| Croscarmellose sodium | 19 |
| Talcum powder | 1 |
The preparation process comprises the following steps: weighing the bulk drugs, glucose monohydrate and croscarmellose sodium according to the prescription amount, premixing the bulk drugs with the glucose monohydrate, uniformly mixing the premix with other auxiliary materials, performing wet granulation, and drying. Adding pulvis Talci, and encapsulating.
Example 3
| Betriciban | 32 |
| Lactose monohydrate | 20 |
| Glucose monohydrate | 35 |
| Croscarmellose sodium | 11 |
| Talcum powder | 2 |
The preparation process comprises the following steps: weighing the bulk drugs, lactose monohydrate, glucose monohydrate and croscarmellose sodium according to the prescription amount, premixing the bulk drugs with the glucose monohydrate, uniformly mixing the premix with other auxiliary materials, performing wet granulation, and drying. Adding pulvis Talci, and encapsulating.
Example 4:
| betriciban | 35 |
| Spray-dried mannitol | 20 |
| Glucose monohydrate | 35 |
| Croscarmellose sodium | 9 |
| Magnesium stearate | 1 |
The preparation process comprises the following steps: weighing the bulk drugs, spray-dried mannitol, glucose monohydrate and croscarmellose sodium according to the prescription amount, premixing the bulk drugs with the glucose monohydrate, uniformly mixing the premix with other auxiliary materials, performing wet granulation, and drying. Adding magnesium stearate, and encapsulating.
Test stability comparison results under accelerated conditions (temperature 40 ℃, relative humidity 75% RH)
Table 1 examples 1 to 3 and comparative examples 1 to 3 betrixaban capsule content and stability data results
It can be seen that the stability of the betrixaban capsules prepared in examples 1 to 4 was good. Therefore, the capsule prepared by the invention has the advantages of simple preparation process, good stability, few auxiliary material types and the like.
Claims (9)
1. A betrixaban capsule comprises the following components in parts by weight:
2. A capsule, BETRIXIBAN Capsule, is prepared by wet granulating, weighing a certain amount of raw materials, filler and disintegrant, mixing, wet granulating with purified water, oven drying, and packaging.
3. The betrixaban capsule of claim 1, wherein the filler is one or more of microcrystalline cellulose, spray dried mannitol, glucose monohydrate, lactose monohydrate.
4. The betrixaban capsule of claim 1, wherein the disintegrant is one or more of low-substituted hydroxypropyl cellulose, croscarmellose sodium, and sodium carboxymethyl starch.
5. The betrixaban capsule of claim 1 wherein the lubricant is one or more of talc and magnesium stearate.
6. The method for preparing betrixaban capsules according to claims 1-2, wherein the raw and auxiliary materials are granulated, and the addition amount of wetting agent for wet granulation is 10% to 25%.
7. The method for preparing betrixaban capsules as claimed in claims 1-2, wherein the temperature for granulating and drying the raw and auxiliary materials is 40-60 ℃.
8. The method for preparing betrixaban capsules according to claims 1-2, wherein the ratio of bulk drug to filler is 1: 1.1-2.0, raw material medicine: the ratio of the disintegrating agent is 1: 0.5 to 1.0.
9. The method for preparing betrixaban capsules according to claims 1-2, wherein the preparation process comprises partially premixing the raw material drug and the filler, and then mixing the premix with other excipients uniformly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910530251.3A CN112107554A (en) | 2019-06-19 | 2019-06-19 | Betricitaban capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910530251.3A CN112107554A (en) | 2019-06-19 | 2019-06-19 | Betricitaban capsule and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112107554A true CN112107554A (en) | 2020-12-22 |
Family
ID=73795569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910530251.3A Pending CN112107554A (en) | 2019-06-19 | 2019-06-19 | Betricitaban capsule and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112107554A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112438958A (en) * | 2020-11-27 | 2021-03-05 | 北京鑫开元医药科技有限公司 | Betrixaban capsule and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104341343A (en) * | 2013-07-24 | 2015-02-11 | 四川海思科制药有限公司 | Crystal forms of betrixaban, and preparing method and uses thereof |
| CN106458905A (en) * | 2014-05-20 | 2017-02-22 | 四川海思科制药有限公司 | Betrixaban salts and preparation method and use thereof |
| WO2018001914A1 (en) * | 2016-06-28 | 2018-01-04 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical capsule composition of rivaroxaban |
-
2019
- 2019-06-19 CN CN201910530251.3A patent/CN112107554A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104341343A (en) * | 2013-07-24 | 2015-02-11 | 四川海思科制药有限公司 | Crystal forms of betrixaban, and preparing method and uses thereof |
| CN106458905A (en) * | 2014-05-20 | 2017-02-22 | 四川海思科制药有限公司 | Betrixaban salts and preparation method and use thereof |
| WO2018001914A1 (en) * | 2016-06-28 | 2018-01-04 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical capsule composition of rivaroxaban |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112438958A (en) * | 2020-11-27 | 2021-03-05 | 北京鑫开元医药科技有限公司 | Betrixaban capsule and preparation method thereof |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201222 |