CN108929321A - A kind of Pa Boxini novel crystal forms - Google Patents
A kind of Pa Boxini novel crystal forms Download PDFInfo
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- CN108929321A CN108929321A CN201810711659.6A CN201810711659A CN108929321A CN 108929321 A CN108929321 A CN 108929321A CN 201810711659 A CN201810711659 A CN 201810711659A CN 108929321 A CN108929321 A CN 108929321A
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- Prior art keywords
- boxini
- crystal forms
- novel crystal
- acetone
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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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 present invention relates to a kind of Pa Boxini (Palbociclib) novel crystal forms, belong to bulk pharmaceutical chemicals preparation technical field.Pa Boxini novel crystal forms of the present invention have a characteristic absorption peak in following ± 0.2 position 2 θ in X-ray powder diffraction figure: 5.98,7.89,10.21,12.68,13.78,16.04,16.74,18.27,18.85,19.52,19.86,20.88,23.02,24.83,26.52,28.22.Crystal form of the present invention has good resistance to bond.
Description
Technical field
The present invention relates to a kind of Pa Boxini (Palbociclib) novel crystal forms, belong to bulk pharmaceutical chemicals preparation technical field.
Background technique
Pa Boxini (Palbociclib), entitled 6- acetyl group -8- cyclopenta -5- methyl -2- [5- (the 1- piperazine of chemistry
Base) pyridine -2- base amino] -8H- pyrido [2-3-d] pyrimidin-7-ones are the treatment metastatic breast cancers of Pfizer's exploitation
New drug, the approval of food and drug administration was obtained within 3rd within 2 months in 2015.
Existing Pa Boxini bulk pharmaceutical chemicals dissolubility is poor, and mobility is bad, and when tabletting, sticking is serious.Therefore, original is ground with glue
The form of capsule lists.Capsule clinic bad adaptability, some patientss are inadaptable to be taken.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of Pa Boxini novel crystal forms, overcome tough defect.
Technical solution:
A kind of Pa Boxini novel crystal forms have characteristic absorption peak in following ± 0.2 position 2 θ in X-ray powder diffraction figure:
5.98、7.89、10.21、12.68、13.78、16.04、16.74、18.27、18.85、19.52、19.86、20.88、23.02、
24.83、26.52、28.22。
Pa Boxini novel crystal forms of the present invention are free of recrystallisation solvent.
The preparation method of Pa Boxini novel crystal forms of the present invention, comprising the following steps:
First step Pa Boxini crude product is dissolved in isopropanol solvent；
Preferably, gained Pa Boxini solution concentration range is 0.08-0.16mg/ml；
Second step is added acetone, stirs evenly, solution temperature is reduced to -5 to 5 DEG C into first step Pa Boxini solution,
Stirring and crystallizing, growing the grain；
Preferably, the amount that acetone is added is the 30% to 46% of first step quantity of solvent；It is preferred that 38%-42%；
Third step filtering, isopropanol-acetone mixed solution washing, 80 DEG C of drying.It is different in the isopropanol-acetone mixed solution
The volume ratio of propyl alcohol and acetone is 3:1.
The utility model has the advantages that the present invention unexpectedly obtains a kind of Pa Boxini novel crystal forms.With good granularity and flowing
Property.Compared with existing Pa Boxini bulk pharmaceutical chemicals, there is no the possibility of sticking during preparing preparation.
Detailed description of the invention
The X-ray powder diffraction figure of Fig. 1 crystal form of the present invention.
Embodiment following embodiment presses prior art preparation with Pa Boxini crude product, and it is 96.65% that HPLC, which detects purity,.
1. 8g Pa Boxini crude product of embodiment is dissolved in 100ml isopropanol solvent, filtering；30ml acetone, stirring is added
Uniformly, solution temperature is reduced to -5 DEG C and kept, stirring and crystallizing, growing the grain 3 hours；Filtering, point 3 shared 30ml isopropanols-
Acetone mixed solution washing, 80 DEG C of drying obtain crystal form of the present invention, and X-ray powder diffraction pattern is shown in that Fig. 1, HPLC detect purity
It is 99.87%, yield 92.13%.
2. 16g Pa Boxini crude product of embodiment is dissolved in 100ml isopropanol solvent, filtering；Acetone 46ml is added, stirs
It mixes uniformly, solution temperature is reduced to 5 DEG C and is kept, stirring and crystallizing, growing the grain 5 hours；Filtering, point 3 shared 36ml isopropanols-
Acetone mixed solution washing, 80 DEG C of drying obtain crystal form of the present invention, and X-ray powder diffraction pattern is shown in that Fig. 1, HPLC detect purity
It is 99.76%, yield 92.86%.
3. 10g Pa Boxini crude product of embodiment is dissolved in 100ml isopropanol solvent, filtering；Acetone 42ml is added, stirs
It mixes uniformly, solution temperature is reduced to 0 DEG C and is kept, stirring and crystallizing, growing the grain 4 hours；Filtering, point 3 shared 35ml cross isopropyl
Alcohol-acetone mixed solution washing, 80 DEG C of drying obtain crystal form of the present invention, and X-ray powder diffraction pattern is shown in Fig. 1, and HPLC detection is pure
Degree is 99.92%, yield 93.16%
Test example 1 with embodiment 1-3 product prepares tablet by following prescription respectively, observes tableting processes, and measure its dissolution
Degree.
Prescription: Pa Boxini 100g, succinic acid 20g, lactose 85g, lauryl sodium sulfate 1.5g, crospovidone 20g,
Magnesium stearate 2.4g.1000 are prepared as follows.
The first step weighs the Pa Boxini of recipe quantity, lauryl sodium sulfate, is added in mixer-granulator, mixing 30
Minute；
Obtained by the second step first step, the succinic acid, lactose, crospovidone of recipe quantity is added, makees adhesive with 50% ethyl alcohol,
Adhesive, stirring, prepares softwood；
Softwood obtained by second step is placed in fluid bed dryer by third step, dry, whole grain；
Obtained by 4th step third step, the magnesium stearate of recipe quantity, tabletting is added.
The appearance of piece and the process of tabletting are observed, observation situation is recorded in table 1.
Table 1
| Embodiment 1 | Embodiment 2 | Embodiment 3 | |
| Appearance, range estimation | It is smooth, no point | It is smooth, no point | It is smooth, no point |
| Sticking is no | Not sticking | Not sticking | Not sticking |
Table 1 illustrates that product of the embodiment of the present invention can obtain good piece of appearance, overcomes existing bulk pharmaceutical chemicals because of the big institute of viscosity
The sticking problem of cause.
Test example 2 is aluminum-plastic packaged respectively respectively and piece each 100 prepared by Example 1-3, is placed in 40 DEG C, phase
In the climatic chamber for being 75% to humidity, measure 0 day respectively, the 30th day dissolution rate, data record is in table 2.
Table 2
2 data of table illustrate that Dissolution of Tablet prepared by crystal form prepared by the embodiment of the present invention meets standards of pharmacopoeia, and are depositing
Stablize during putting, even hot and humid environment and stable.
Claims (6)
1. a kind of Pa Boxini novel crystal forms, characterized in that there is spy in following ± 0.2 position 2 θ in its X-ray powder diffraction figure
Levy absorption peak: 5.98,7.89,10.21,12.68,13.78,16.04,16.74,18.27,18.85,19.52,19.86,
20.88、23.02、24.83、26.52、28.22。
2. according to Pa Boxini novel crystal forms described in claim 1, characterized in that be free of recrystallisation solvent.
3. the preparation method of Pa Boxini novel crystal forms described in claim 1, characterized in that the following steps are included:
First step Pa Boxini crude product is dissolved in isopropanol solvent；
Second step is added acetone, stirs evenly, solution temperature is reduced to -5 to 5 DEG C into first step Pa Boxini solution,
Stirring and crystallizing, growing the grain；
Third step filtering, isopropanol-acetone mixed solution washing, 80 DEG C dry, different in the isopropanol-acetone mixed solution
The volume ratio of propyl alcohol and acetone is 3:1.
4. the preparation method of Pa Boxini novel crystal forms according to claim 3, characterized in that Pa Boxini obtained by the first step is molten
Liquid concentration range is 0.08-0.16mg/ml.
5. the preparation method of Pa Boxini novel crystal forms according to claim 3, characterized in that the amount that acetone is added is the first step
The 30% to 46% of quantity of solvent.
6. the preparation method of Pa Boxini novel crystal forms according to claim 3, characterized in that the amount that acetone is added is the first step
The 38%-42% of quantity of solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810711659.6A CN108929321A (en) | 2018-07-03 | 2018-07-03 | A kind of Pa Boxini novel crystal forms |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810711659.6A CN108929321A (en) | 2018-07-03 | 2018-07-03 | A kind of Pa Boxini novel crystal forms |
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| Publication Number | Publication Date |
|---|---|
| CN108929321A true CN108929321A (en) | 2018-12-04 |
Family
ID=64447686
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| Application Number | Title | Priority Date | Filing Date |
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| CN201810711659.6A Withdrawn CN108929321A (en) | 2018-07-03 | 2018-07-03 | A kind of Pa Boxini novel crystal forms |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114149426A (en) * | 2021-12-13 | 2022-03-08 | 江苏海洋大学 | Pabociclib pharmaceutical co-crystal and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016090257A1 (en) * | 2014-12-05 | 2016-06-09 | Crystal Pharmatech Inc. | Salts and crystalline forms of 6-acetyl-8-cyclopentyl-5-methyl-2((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d] pyrimidin-7(8h)-one (palbociclib) |
| CN106608876A (en) * | 2015-10-21 | 2017-05-03 | 新发药业有限公司 | Preparation method of high-purity palbociclib |
| CN106632311A (en) * | 2015-11-02 | 2017-05-10 | 上海科胜药物研发有限公司 | Preparation method of palbociclib crystal form A and crystal form B |
| CN106866666A (en) * | 2017-04-06 | 2017-06-20 | 山东裕欣药业有限公司 | A kind of Pa Boxini crystal-form compounds and preparation method thereof |
| CN107759596A (en) * | 2017-12-05 | 2018-03-06 | 安庆奇创药业有限公司 | A kind of synthesis Pa Boxini method |
| CN108017630A (en) * | 2016-10-31 | 2018-05-11 | 上海创诺制药有限公司 | A kind of preparation method of small specific surface product Pa Boxini free alkalis |
-
2018
- 2018-07-03 CN CN201810711659.6A patent/CN108929321A/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016090257A1 (en) * | 2014-12-05 | 2016-06-09 | Crystal Pharmatech Inc. | Salts and crystalline forms of 6-acetyl-8-cyclopentyl-5-methyl-2((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d] pyrimidin-7(8h)-one (palbociclib) |
| CN106608876A (en) * | 2015-10-21 | 2017-05-03 | 新发药业有限公司 | Preparation method of high-purity palbociclib |
| CN106632311A (en) * | 2015-11-02 | 2017-05-10 | 上海科胜药物研发有限公司 | Preparation method of palbociclib crystal form A and crystal form B |
| CN108017630A (en) * | 2016-10-31 | 2018-05-11 | 上海创诺制药有限公司 | A kind of preparation method of small specific surface product Pa Boxini free alkalis |
| CN106866666A (en) * | 2017-04-06 | 2017-06-20 | 山东裕欣药业有限公司 | A kind of Pa Boxini crystal-form compounds and preparation method thereof |
| CN107759596A (en) * | 2017-12-05 | 2018-03-06 | 安庆奇创药业有限公司 | A kind of synthesis Pa Boxini method |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114149426A (en) * | 2021-12-13 | 2022-03-08 | 江苏海洋大学 | Pabociclib pharmaceutical co-crystal and preparation method thereof |
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Application publication date: 20181204 |