CN106518854A - Preparation method of Vilazodone hydrochloride crystal form IV - Google Patents
Preparation method of Vilazodone hydrochloride crystal form IV Download PDFInfo
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- CN106518854A CN106518854A CN201610839971.4A CN201610839971A CN106518854A CN 106518854 A CN106518854 A CN 106518854A CN 201610839971 A CN201610839971 A CN 201610839971A CN 106518854 A CN106518854 A CN 106518854A
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- preparation
- crystal formation
- vilazodone hydrochloride
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- vilazodone
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of drug development, and particularly relates to a preparation method of a Vilazodone hydrochloride crystal form IV. The Vilazodone hydrochloride crystal form IV is recognized as an advantaged crystal form of drug preparations, and has the characteristics of relatively stable crystal form, capability of best playing the role of treatment of diseases and low toxic and side effects. The preparation method for transformation of non-advantaged crystal forms (I, II, III, XI and VIII) of Vilazodone hydrochloride into the advantaged crystal form IV is specifically studied. The preparation method has the advantages of simple operation and good process reproducibility, the clinical treatment efficacy of Vilazodone hydrochloride can be improved by the research, and the research is a work very useful to effective and safe public drug administration.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to antidepressant Vilazodone Hydrochloride crystal formation IV preparation technology
Research and development.
Background technology
Vilazodone (Vilazodone), chemical name：5- [4- [4- (5- cyano-1 H-indol -3- bases) butyl] -1- piperazines
Base] -2- benzofuran oxamides, researched and developed by forest laboratory drugmaker and Merck KGaA company jointly, in 2011 in FDA
Granted listing, for treating severe adult's depression.The medical instrument has 5-HT1AAcceptor portion agonist and selective serotonin are again
Uptake inhibitor double activity, Vilazodone Hydrochloride have it is rapid-action, do not increase body weight, do not affect sexual function, better tolerance, no
It is good reaction it is little the characteristics of make it have very big prospect.Its structural formula is as follows：
The research of polymorph in pharmaceuticals is very important group in new drug development, technological design and pharmaceutical dosage form design process
Into part.The phenomenon of a certain polymorph in pharmaceuticals and the property of various crystal formations is fully understood by, for medicament research and development worker is according to life
Thing availability and stability have greatly help when the preparation technology of bulk drug and preparation is designed.Also ensure that medicine simultaneously
Quality, the safe medication for patient provides sound assurance.When solid medicine has polymorphism, and different crystal forms shape
When state can produce impact to the validity of medicine, security or quality, reply medicine solid pharmaceutical preparation, semisolid preparation, supensoid agent
Medicinal crystal-form state of matter in is qualitatively or quantitatively controlled.The medicinal crystal-form of medicine answers selective advantage crystal formation (to work as medicine
When there are various crystal form states, good, safe and stable property height of clinical efficacy of crystal-form substances state etc., and it is adapted to drug development
Crystal formation), and keep crystal form state in preparation to be advantage crystal formation, with ensure the validity of medicine, security with it is quality controllable.
Vilazodone Hydrochloride belongs to polymorph medicine, its Central Plains consult and deliberate patent CN1516699 researched and developed hydrochloric acid Wella assistant
The serial crystal formation of ketone, including 14 kinds of crystal formations such as crystal formation I, II, III, IV, and has explicitly pointed out crystal formation IV as solid pharmaceutical preparation
Obvious advantage, therefore to study the preparation of Vilazodone Hydrochloride crystal formation IV will be significantly something, not only improve
The quality of imitation medicine, while provide sound assurance for numerous people drug safety.
The content of the invention
The present invention mainly have studied the preparation method of Vilazodone Hydrochloride crystal formation IV：By stir in the way of make methyl alcohol from it is different
The medicine of crystal formation is fully mixed, filter cake high temperature drying after filtration, obtains final product the vilazodone of target crystal formation.
Methyl alcohol is 10 with the volume mass ratio of medicine:1~40:1, wherein methyl alcohol is most preferably 15 with injection volume mass ratio:
1；Mixing time is 1 ~ 24 hour, and optimal mixing time is 10 hours.
Filter cake vacuum drying obtained by filtering, baking temperature is 60 ~ 150 DEG C, and optimum drying temperature is 110 DEG C.
Above-described solvent agent is commercially available to be easy to get and with low cost.
The present invention specifically have studied the non-advantage crystal formation (I, II, III, Ⅺ and VIII) of Vilazodone Hydrochloride and transform into advantage
The preparation method of crystal formation IV.Described preparation method operating process is simple, technique reappearance is good, can by our research
The clinical efficacy of Vilazodone Hydrochloride is improve, will be one and be very useful to public's work safe and effective for medication.
Description of the drawings
1. embodiment of accompanying drawing, 2 Vilazodone Hydrochloride crystal formation II；
2. embodiment of accompanying drawing, 3 Vilazodone Hydrochloride crystal formation III；
3. embodiment of accompanying drawing, 4 Vilazodone Hydrochloride crystal formation VIII；
4. embodiment of accompanying drawing, 5 Vilazodone Hydrochloride crystal formation Ⅺ；
5. embodiment of accompanying drawing, 6 Vilazodone Hydrochloride crystal formation IV.
Embodiment
The present invention is described in more detail below in conjunction with example, but not as limitation of the present invention.
Embodiment 1
1 g vilazodones (99 % of HPLC) are completely dissolved in acetone (AR, 50 mL), hydrochloric acid are slowly added dropwise thereto water-soluble
Liquid (1 M, 2 mL), during a large amount of white precipitates generate, to remove solvent, 40 DEG C are vacuum dried to obtain hydrochloric acid Wella to decompression suction filtration
Assistant ketone (crystal formation I).
Embodiment 2
1 g vilazodones (99 % of HPLC) are completely dissolved in tetrahydrofuran (AR, 20 mL), hydrochloric acid is slowly added dropwise thereto
The aqueous solution (2 M, 0.5 mL), during a large amount of white precipitates generate, to remove solvent, 40 DEG C are vacuum dried to obtain salt to decompression suction filtration
Sour vilazodone (crystal formation II).
Embodiment 3
1 g vilazodones (99 % of HPLC) are completely dissolved in tetrahydrofuran (AR, 20 mL), hydrochloric acid is slowly added dropwise thereto
The aqueous solution (2 M, 0.5 mL), during a large amount of white precipitates generate, to remove solvent, 80 DEG C are vacuum dried to obtain salt to decompression suction filtration
Sour vilazodone (crystal formation III).
Embodiment 4
1 g vilazodones (99 % of HPLC) are completely dissolved in tetrahydrofuran (AR, 20 mL), hydrochloric acid is slowly added dropwise thereto
The aqueous solution (2 M, 0.5 mL), during a large amount of white precipitates generate, to remove solvent, 80 DEG C are vacuum dried to obtain salt to decompression suction filtration
Sour vilazodone, stirs gained Vilazodone Hydrochloride and water fully miscible 10 hours, and, to remove solvent, 40 DEG C true for decompression suction filtration
Empty dry Vilazodone Hydrochloride (crystal formation VIII).
Embodiment 5
1 g vilazodones (99 % of HPLC) are completely dissolved in tetrahydrofuran (AR, 20 mL), hydrochloric acid is slowly added dropwise thereto
The aqueous solution (2 M, 0.5 mL), during a large amount of white precipitates generate, to remove solvent, 80 DEG C are vacuum dried to obtain salt to decompression suction filtration
Sour vilazodone, by the fully miscible stirring 10 hours of gained Vilazodone Hydrochloride and methyl alcohol, decompression suction filtration to remove solvent, 40 DEG C
It is vacuum dried to obtain Vilazodone Hydrochloride (crystal formation Ⅺ).
Embodiment 6
Stir Vilazodone Hydrochloride (obtained by above example) obtained by 1 g and methyl alcohol (15 mL) fully miscible 10 hours, decompression
To remove solvent, 110 DEG C are vacuum dried to obtain Vilazodone Hydrochloride (crystal formation IV) to suction filtration.
Claims (5)
1. a kind of preparation method of Vilazodone Hydrochloride crystal formation IV, it is characterised in that：Methyl alcohol is made in the way of stirring with the not isomorphous
The medicine of type is fully mixed, filter cake high temperature drying after filtration, obtains final product the vilazodone of crystal formation IV.
2. the preparation method of crystal formation IV according to claim 1, it is characterised in that methyl alcohol is 10 with the volume mass ratio of medicine:
1~40:1, mixing time is 1 ~ 24 hour.
3. according to claim 1 and 2 crystal formation IV preparation method, methyl alcohol and injection volume mass ratio preferably 15:1, stirring
Preferably 10 hours time.
4. the preparation method of crystal formation IV according to claim 1, the filter cake vacuum drying obtained by filtering, baking temperature is
60~150℃。
5. according to claim 1 and 4 crystal formation IV preparation method, preferably 110 DEG C of baking temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610839971.4A CN106518854A (en) | 2016-09-21 | 2016-09-21 | Preparation method of Vilazodone hydrochloride crystal form IV |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610839971.4A CN106518854A (en) | 2016-09-21 | 2016-09-21 | Preparation method of Vilazodone hydrochloride crystal form IV |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106518854A true CN106518854A (en) | 2017-03-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610839971.4A Pending CN106518854A (en) | 2016-09-21 | 2016-09-21 | Preparation method of Vilazodone hydrochloride crystal form IV |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109503560A (en) * | 2017-09-14 | 2019-03-22 | 北京万全德众医药生物技术有限公司 | The preparation method of Ⅺ crystal form of Vilazodone Hydrochloride |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1516699A (en) * | 2001-06-19 | 2004-07-28 | Ĭ��ר���ɷ�����˾ | Polymorphic forms of 1-4-(5-cyanoindol-3-yl) butyl-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride |
| CN103772368A (en) * | 2012-10-24 | 2014-05-07 | 杭州和泽医药科技有限公司 | Preparation method and application of vilazodone hydrochloride IV crystal |
| US20140303185A1 (en) * | 2013-04-09 | 2014-10-09 | Orchid Chemicals & Pharmaceuticals Limited | Novel polymorphs of vilazodone hydrochloride |
| WO2015037010A1 (en) * | 2013-09-13 | 2015-03-19 | Symed Labs Limited | Preparation of vilazodone hydrochloride crystalline form iv |
| CN105820157A (en) * | 2015-01-09 | 2016-08-03 | 石药集团中奇制药技术（石家庄）有限公司 | Vilazodone hydrochloride crystal form and preparation method thereof |
-
2016
- 2016-09-21 CN CN201610839971.4A patent/CN106518854A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1516699A (en) * | 2001-06-19 | 2004-07-28 | Ĭ��ר���ɷ�����˾ | Polymorphic forms of 1-4-(5-cyanoindol-3-yl) butyl-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride |
| CN103772368A (en) * | 2012-10-24 | 2014-05-07 | 杭州和泽医药科技有限公司 | Preparation method and application of vilazodone hydrochloride IV crystal |
| US20140303185A1 (en) * | 2013-04-09 | 2014-10-09 | Orchid Chemicals & Pharmaceuticals Limited | Novel polymorphs of vilazodone hydrochloride |
| WO2015037010A1 (en) * | 2013-09-13 | 2015-03-19 | Symed Labs Limited | Preparation of vilazodone hydrochloride crystalline form iv |
| CN105820157A (en) * | 2015-01-09 | 2016-08-03 | 石药集团中奇制药技术（石家庄）有限公司 | Vilazodone hydrochloride crystal form and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109503560A (en) * | 2017-09-14 | 2019-03-22 | 北京万全德众医药生物技术有限公司 | The preparation method of Ⅺ crystal form of Vilazodone Hydrochloride |
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