CN106265571A - A kind of preparation method of olanzapine tablet - Google Patents
A kind of preparation method of olanzapine tablet Download PDFInfo
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- CN106265571A CN106265571A CN201610799403.6A CN201610799403A CN106265571A CN 106265571 A CN106265571 A CN 106265571A CN 201610799403 A CN201610799403 A CN 201610799403A CN 106265571 A CN106265571 A CN 106265571A
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- olanzapine
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- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- Pharmacology & Pharmacy (AREA)
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- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention proposes the preparation method of a kind of olanzapine tablet, including olanzapine, diluent, disintegrating agent, binding agent, wherein olanzapine passes through rough and refines for twice, olanzapine medicinal crystal-form I purity >=99.5% obtained, the final disintegration of tablet speed prepared is fast, dissolution is high, and the breakage rate of tablet is low, and production efficiency is high.
Description
Technical field
The present invention relates to pharmaceutical preparations technology field, be specifically related to the preparation method of a kind of olanzapine tablet.
Background technology
Along with the quickening of people's rhythm of life, pressure increases the most therewith, and mental sickness becomes a kind of common disease, spirit point
Splitting disease is exactly the most most commonly seen one, and it suffers from patient's thinking, perception, Bewu βtseinstrubung, and Relapse rate shows effect and the most lifelong
Not healing, in China, schizophrenia individually a kind of mental sickness, its treatment rate is only about 30%, the most safely and effectively essence
God's class medicine is the primary condition improving this present situation.Olanzapine (Olanzapine) chemical name is 2-methyl-4-(4-first
Base-1-piperazinyl)-10H-thieno 2,3-b] [1,5] benzodiazepine, what Lilly company of the oil U.S. developed is used for essence
God Split disease and other have the serious positive symptom and/or negative symptoms mental sickness acute stage and maintain the phase treatment, also
The Secondary cases affective symptom of schizophrenia and relevant disease can be alleviated.At present for medicinal crystalline substance in the preparation process of olanzapine
The purity of type I is low, and therapeutic effect is poor, and as oral tablet, yield rate is low, and easy rhegma, production efficiency is low.
Summary of the invention
For the problem of above-mentioned existence, the present invention proposes the preparation method of a kind of olanzapine tablet, and the tablet of generation becomes
Type rate is high, and therapeutic effect is strong.
In order to realize above-mentioned purpose, the present invention uses following technical scheme:
The preparation method of a kind of olanzapine tablet, including olanzapine, diluent, disintegrating agent, binding agent, its preparation process is such as
Under:
1) preparation of olanzapine crude product
By 4-amino-2-methyl-10H-thieno [2,3,6] [1,5] benzodiazepine hydrochlorate and the N-first of excess
Base piperazine refluxes 1.8-2h under the conditions of 140 DEG C, and then the N methyl piperazine of decompression distillation excess, obtains olanzapine crude product；
2) olanzapine crude product primary purification
Being blended by weight 1:10 with recrystallization solvent by olanzapine crude product, heated and stirred is uniform, is back to olanzapine thick
Product add, after being completely dissolved, the adsorbent accounting for backflow weight 5-8%, stir 3-5min, filtered while hot, retain filtrate, and room temperature is quiet
Put 15-20h, filter and also wash 3-4 time with recrystallization solvent, retain crystal, dried obtain recrystallization crystal of olanzapine；
3) olanzapine crude product secondary refining
Recrystallization crystal of olanzapine is blended, then with step 2 by weight 1:12 with recrystallization solvent) operation phase
With, dried olanzapine；
4) preparation of olanzapine tablet
Olanzapine, diluent, disintegrating agent, binding agent being blended, be then placed in pelletize in high shear granulator, pelletize completes
After carry out fluid bed drying, cross 20 mesh sieve granulate, then be added thereto to magnesium stearate and be blended, tabletting,.
Preferably, described diluent is lactose, and described disintegrating agent is hydroxypropyl cellulose, and described binding agent is polyethylene pyrrole
Pyrrolidone or polyvidone or a combination of both thing.
Preferably, described olanzapine tablet also includes correctives, preservative and disintegrate auxiliary agent.
Preferably, described disintegrate auxiliary agent is the compositions of sodium carboxymethyl cellulose and beta-schardinger dextrin-.
Preferably, step 2) and step 3) in the compositions that recrystallization solvent is ethanol and ethyl acetate, both quality
Ratio is 1:1.
Preferably, described step 2) and step 3) in adsorbent be bamboo charcoal powder.
Preferably, described step 2) and step 3) in reflux temperature be 79 DEG C.
Owing to using above-mentioned technical scheme, the invention has the beneficial effects as follows: with 4-amino-2-methyl-10H-thieno
The N methyl piperazine of [2,3,6] [1,5] benzodiazepine hydrochlorate and excess is crude drug, under conditions of organic solvent-free
Directly back flow reaction, obtains the yield of olanzapine crude product up to 99.8%, then by olanzapine through twice recrystallizing and refining, obtains
Olanzapine medicinal crystal-form I purity >=99.5%, average yield is 72.6%, and the final disintegration of tablet speed prepared is fast, dissolution
Height, and the breakage rate of tablet is low, improves production efficiency.
Detailed description of the invention
For making the purpose of the embodiment of the present invention, technical scheme and advantage clearer, below in conjunction with the embodiment of the present invention,
Technical scheme in the embodiment of the present invention is clearly and completely described.Based on embodiments of the invention, the common skill in this area
The every other embodiment that art personnel are obtained under not making creative work premise, broadly falls into the model of present invention protection
Enclose.
Embodiment 1:
The preparation method of a kind of olanzapine tablet, including olanzapine, diluent, disintegrating agent, binding agent, its preparation process is such as
Under:
1) preparation of olanzapine crude product
By 4-amino-2-methyl-10H-thieno [2,3,6] [1,5] benzodiazepine hydrochlorate and the N-first of excess
Base piperazine refluxes 1.8h under the conditions of 140 DEG C, and then the N methyl piperazine of decompression distillation excess, obtains olanzapine crude product；
2) olanzapine crude product primary purification
Being blended by weight 1:10 with recrystallization solvent by olanzapine crude product, heated and stirred is uniform, is back to olanzapine thick
Product add, after being completely dissolved, the adsorbent accounting for backflow weight 5%, stir 4min, filtered while hot, retain filtrate, and room temperature stands
16h, filters and also washs 3 times with recrystallization solvent, retains crystal, dried recrystallization crystal of olanzapine；
3) olanzapine crude product secondary refining
Recrystallization crystal of olanzapine is blended, then with step 2 by weight 1:12 with recrystallization solvent) operation phase
With, dried olanzapine；
4) preparation of olanzapine tablet
Olanzapine, diluent, disintegrating agent, binding agent being blended, be then placed in pelletize in high shear granulator, pelletize completes
After carry out fluid bed drying, cross 20 mesh sieve granulate, then be added thereto to magnesium stearate and be blended, tabletting,.
Wherein, binding agent is polyvinylpyrrolidone.
Embodiment 2:
The preparation method of a kind of olanzapine tablet, including olanzapine, diluent, disintegrating agent, binding agent, its preparation process is such as
Under:
1) preparation of olanzapine crude product
By 4-amino-2-methyl-10H-thieno [2,3,6] [1,5] benzodiazepine hydrochlorate and the N-first of excess
Base piperazine refluxes 2h under the conditions of 140 DEG C, and then the N methyl piperazine of decompression distillation excess, obtains olanzapine crude product；
2) olanzapine crude product primary purification
Being blended by weight 1:10 with recrystallization solvent by olanzapine crude product, heated and stirred is uniform, is back to olanzapine thick
Product add, after being completely dissolved, the adsorbent accounting for backflow weight 6%, stir 3min, filtered while hot, retain filtrate, and room temperature stands
18h, filters and also washs 4 times with recrystallization solvent, retains crystal, dried recrystallization crystal of olanzapine；
3) olanzapine crude product secondary refining
Recrystallization crystal of olanzapine is blended, then with step 2 by weight 1:12 with recrystallization solvent) operation phase
With, dried olanzapine；
4) preparation of olanzapine tablet
Olanzapine, diluent, disintegrating agent, binding agent being blended, be then placed in pelletize in high shear granulator, pelletize completes
After carry out fluid bed drying, cross 20 mesh sieve granulate, then be added thereto to magnesium stearate and be blended, tabletting,.
Wherein, binding agent is polyvidone.
Embodiment 3:
The preparation method of a kind of olanzapine tablet, including olanzapine, diluent, disintegrating agent, binding agent, its preparation process is such as
Under:
1) preparation of olanzapine crude product
By 4-amino-2-methyl-10H-thieno [2,3,6] [1,5] benzodiazepine hydrochlorate and the N-first of excess
Base piperazine refluxes 1.9h under the conditions of 140 DEG C, and then the N methyl piperazine of decompression distillation excess, obtains olanzapine crude product；
2) olanzapine crude product primary purification
Being blended by weight 1:10 with recrystallization solvent by olanzapine crude product, heated and stirred is uniform, is back to olanzapine thick
Product add, after being completely dissolved, the adsorbent accounting for backflow weight 7%, stir 5min, filtered while hot, retain filtrate, and room temperature stands
20h, filters and also washs 3 times with recrystallization solvent, retains crystal, dried recrystallization crystal of olanzapine；
3) olanzapine crude product secondary refining
Recrystallization crystal of olanzapine is blended, then with step 2 by weight 1:12 with recrystallization solvent) operation phase
With, dried olanzapine；
4) preparation of olanzapine tablet
Olanzapine, diluent, disintegrating agent, binding agent being blended, be then placed in pelletize in high shear granulator, pelletize completes
After carry out fluid bed drying, cross 20 mesh sieve granulate, then be added thereto to magnesium stearate and be blended, tabletting,.
Wherein, binding agent is polyvinylpyrrolidone.
Embodiment 4:
The preparation method of a kind of olanzapine tablet, including olanzapine, diluent, disintegrating agent, binding agent, its preparation process is such as
Under:
1) preparation of olanzapine crude product
By 4-amino-2-methyl-10H-thieno [2,3,6] [1,5] benzodiazepine hydrochlorate and the N-first of excess
Base piperazine refluxes 1.8h under the conditions of 140 DEG C, and then the N methyl piperazine of decompression distillation excess, obtains olanzapine crude product；
2) olanzapine crude product primary purification
Being blended by weight 1:10 with recrystallization solvent by olanzapine crude product, heated and stirred is uniform, is back to olanzapine thick
Product add, after being completely dissolved, the adsorbent accounting for backflow weight 6%, stir 3min, filtered while hot, retain filtrate, and room temperature stands
15h, filters and also washs 4 times with recrystallization solvent, retains crystal, dried recrystallization crystal of olanzapine；
3) olanzapine crude product secondary refining
Recrystallization crystal of olanzapine is blended, then with step 2 by weight 1:12 with recrystallization solvent) operation phase
With, dried olanzapine；
4) preparation of olanzapine tablet
Olanzapine, diluent, disintegrating agent, binding agent being blended, be then placed in pelletize in high shear granulator, pelletize completes
After carry out fluid bed drying, cross 20 mesh sieve granulate, then be added thereto to magnesium stearate and be blended, tabletting,.
Wherein, binding agent is the compositions of polyvinylpyrrolidone and polyvidone.
Embodiment 5:
The preparation method of a kind of olanzapine tablet, including olanzapine, diluent, disintegrating agent, binding agent, its preparation process is such as
Under:
1) preparation of olanzapine crude product
By 4-amino-2-methyl-10H-thieno [2,3,6] [1,5] benzodiazepine hydrochlorate and the N-first of excess
Base piperazine refluxes 2h under the conditions of 140 DEG C, and then the N methyl piperazine of decompression distillation excess, obtains olanzapine crude product；
2) olanzapine crude product primary purification
Being blended by weight 1:10 with recrystallization solvent by olanzapine crude product, heated and stirred is uniform, is back to olanzapine thick
Product add, after being completely dissolved, the adsorbent accounting for backflow weight 8%, stir 4min, filtered while hot, retain filtrate, and room temperature stands
17h, filters and also washs 3 times with recrystallization solvent, retains crystal, dried recrystallization crystal of olanzapine；
3) olanzapine crude product secondary refining
Recrystallization crystal of olanzapine is blended, then with step 2 by weight 1:12 with recrystallization solvent) operation phase
With, dried olanzapine；
4) preparation of olanzapine tablet
Olanzapine, diluent, disintegrating agent, binding agent being blended, be then placed in pelletize in high shear granulator, pelletize completes
After carry out fluid bed drying, cross 20 mesh sieve granulate, then be added thereto to magnesium stearate and be blended, tabletting,.
Wherein, binding agent is polyvidone.
Embodiment 6:
The preparation method of a kind of olanzapine tablet, including olanzapine, diluent, disintegrating agent, binding agent, its preparation process is such as
Under:
1) preparation of olanzapine crude product
By 4-amino-2-methyl-10H-thieno [2,3,6] [1,5] benzodiazepine hydrochlorate and the N-first of excess
Base piperazine refluxes 1.9h under the conditions of 140 DEG C, and then the N methyl piperazine of decompression distillation excess, obtains olanzapine crude product；
2) olanzapine crude product primary purification
Being blended by weight 1:10 with recrystallization solvent by olanzapine crude product, heated and stirred is uniform, is back to olanzapine thick
Product add, after being completely dissolved, the adsorbent accounting for backflow weight 5%, stir 5min, filtered while hot, retain filtrate, and room temperature stands
16h, filters and also washs 4 times with recrystallization solvent, retains crystal, dried recrystallization crystal of olanzapine；
3) olanzapine crude product secondary refining
Recrystallization crystal of olanzapine is blended, then with step 2 by weight 1:12 with recrystallization solvent) operation phase
With, dried olanzapine；
4) preparation of olanzapine tablet
Olanzapine, diluent, disintegrating agent, binding agent being blended, be then placed in pelletize in high shear granulator, pelletize completes
After carry out fluid bed drying, cross 20 mesh sieve granulate, then be added thereto to magnesium stearate and be blended, tabletting,.
Wherein, binding agent is the compositions of polyvinylpyrrolidone and polyvidone.
Above example only in order to technical scheme to be described, is not intended to limit；Although with reference to previous embodiment
The present invention is described in detail, it will be understood by those within the art that: it still can be to aforementioned each enforcement
Technical scheme described in example is modified, or wherein portion of techniques feature is carried out equivalent；And these amendment or
Replace, do not make the essence of appropriate technical solution depart from the spirit and scope of various embodiments of the present invention technical scheme.
Claims (7)
1. the preparation method of an olanzapine tablet, it is characterised in that include olanzapine, diluent, disintegrating agent, binding agent, its
Preparation process is as follows:
1) preparation of olanzapine crude product
By 4-amino-2-methyl-10H-thieno [2,3,6] [1,5] benzodiazepine hydrochlorate and the N-methyl piperazine of excess
Piperazine refluxes 1.8-2h under the conditions of 140 DEG C, and then the N methyl piperazine of decompression distillation excess, obtains olanzapine crude product；
2) olanzapine crude product primary purification
Being blended by weight 1:10 with recrystallization solvent by olanzapine crude product, heated and stirred is uniform, is back to olanzapine crude product complete
Adding the adsorbent accounting for backflow weight 5-8% after CL, stir 3-5min, filtered while hot, retain filtrate, room temperature stands
15-20h, filters and also washs 3-4 time with recrystallization solvent, retains crystal, dried obtains recrystallization crystal of olanzapine；
3) olanzapine crude product secondary refining
Recrystallization crystal of olanzapine and recrystallization solvent are blended, then with step 2 by weight 1:12) operate identical,
Dried olanzapine；
4) preparation of olanzapine tablet
Olanzapine, diluent, disintegrating agent, binding agent being blended, be then placed in pelletize in high shear granulator, pelletize completes laggard
Row fluid bed drying, crosses 20 mesh sieve granulate, then it is blended to be added thereto to magnesium stearate, tabletting,.
The preparation method of olanzapine tablet the most according to claim 1, it is characterised in that: described diluent is lactose, institute
Stating disintegrating agent is hydroxypropyl cellulose, and described binding agent is polyvinylpyrrolidone or polyvidone or a combination of both thing.
The preparation method of olanzapine tablet the most according to claim 1, it is characterised in that: described olanzapine tablet also includes
Correctives, preservative and disintegrate auxiliary agent.
The preparation method of olanzapine tablet the most according to claim 3, it is characterised in that: described disintegrate auxiliary agent is carboxymethyl
Sodium cellulosate and the compositions of beta-schardinger dextrin-.
The preparation method of olanzapine tablet the most according to claim 1, it is characterised in that: step 2) and step 3) in weight
Recrystallisation solvent is the compositions of ethanol and ethyl acetate, and both mass ratioes are 1:1.
The preparation method of olanzapine tablet the most according to claim 1, it is characterised in that: described step 2) and step 3) in
Adsorbent be bamboo charcoal powder.
The preparation method of olanzapine tablet the most according to claim 1, it is characterised in that: described step 2) and step 3) in
Reflux temperature is 79 DEG C.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610799403.6A CN106265571A (en) | 2016-08-31 | 2016-08-31 | A kind of preparation method of olanzapine tablet |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109456336A (en) * | 2017-09-06 | 2019-03-12 | 万全万特制药江苏有限公司 | The refining methd of Olanzapine |
| CN109498578A (en) * | 2017-09-14 | 2019-03-22 | 万全万特制药江苏有限公司 | Stable Olanzapine composition and preparation method thereof |
| CN112110935A (en) * | 2019-06-20 | 2020-12-22 | 北京万全德众医药生物技术有限公司 | Preparation method of olanzapine crystal form II |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030125322A1 (en) * | 2001-12-24 | 2003-07-03 | Sun Parmaceutical Industries Limited | Crystalline form I of 2-methyl-4-(4-methyl-1-piperazinyl) 10H thieno [2,3-b][1,5]benzodiazepine |
| WO2003097650A1 (en) * | 2002-05-17 | 2003-11-27 | Institut Farmaceutyczny | Methods for preparation of olanzapine polymorphic form i |
-
2016
- 2016-08-31 CN CN201610799403.6A patent/CN106265571A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030125322A1 (en) * | 2001-12-24 | 2003-07-03 | Sun Parmaceutical Industries Limited | Crystalline form I of 2-methyl-4-(4-methyl-1-piperazinyl) 10H thieno [2,3-b][1,5]benzodiazepine |
| WO2003097650A1 (en) * | 2002-05-17 | 2003-11-27 | Institut Farmaceutyczny | Methods for preparation of olanzapine polymorphic form i |
Non-Patent Citations (3)
| Title |
|---|
| 刘召鹏: "奥氮平原料药的制备及质量控制", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
| 夏学军等: "奥氮平片剂的处方研究", 《中国药学杂志》 * |
| 平其能等: "《尤特奇（聚甲基丙烯酸酯）应用技术指南》", 31 August 2009, 化学工业出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109456336A (en) * | 2017-09-06 | 2019-03-12 | 万全万特制药江苏有限公司 | The refining methd of Olanzapine |
| CN109498578A (en) * | 2017-09-14 | 2019-03-22 | 万全万特制药江苏有限公司 | Stable Olanzapine composition and preparation method thereof |
| CN112110935A (en) * | 2019-06-20 | 2020-12-22 | 北京万全德众医药生物技术有限公司 | Preparation method of olanzapine crystal form II |
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Application publication date: 20170104 |