CN108653231A - Composition and preparation method thereof containing bruton's tyrosine kinase inhibitor - Google Patents
Composition and preparation method thereof containing bruton's tyrosine kinase inhibitor Download PDFInfo
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Abstract
The present invention is the composition and preparation method thereof containing bruton's tyrosine kinase inhibitor, is related to a kind of Pharmaceutical composition and preparation method thereof containing formula (I) compound or its pharmaceutically acceptable salt.Composition dissolution rate produced by the present invention is good, stable quality, and can meet clinical application simultaneously, the requirements such as patient's compliance.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, are related to one kind and containing bruton's tyrosine kinase (Bruton ' s tyrosine
Kinase, Btk) inhibitor be active constituent pharmaceutical composition and preparation method thereof.
Background technology
Protein kinase, the maximum family in mankind's enzyme, including considerably beyond 500 kinds of protein.Particularly, tyrosine kinase
Phenol moieties of the phosphorylating protein in tyrosine residue.Family tyrosine kinase includes control cell growth, migration and differentiation
Member.Abnormal kinase activity has been directed to many human diseases, including cancer, autoimmune disease and inflammatory disease.
Btk is the member of tyrosine kinase Tec families, and shows it is that early stage B cell is formed and mature B cell activates
With key regulator (Khan etc., Immunity 1995,3 of survival：283；Ellmeier etc., J.Exp.Med.2000192：
1611).B cell leads to the biological result of wide scope by the signal transduction of B-cell receptor (BCR), and these results depend on B
The stage of development of cell.The size of BCR signals and duration must accurately be adjusted.The signal that abnormal BCR is mediated
(deregulated) B cell that transduction can cause mistake to adjust activates and/or the formation of pathogenic autoantibodies, this causes more
Kind autoimmune and/or diseases associated with inflammation.
Evidence about effects of the Btk in autoimmune disease and inflammatory disease is via Btk- deficient mice patterns
It provides.In the preclinical mouse model of systemic loupus erythematosus (SLE), Btk- deficient mices show significantly changing for progression of disease
It is kind.In addition, arthritis that Btk- deficient mices lure collagen it is resistant (Jansson and Holmdahl,
Clin.Exp.Immunol.1993,94：459).Dosage of the verified selectivity Btk inhibitor in arthritis mouse model
Dependence effect (Chem.Med.Chem.2007 such as Pan, 2：58-61).
Btk is also expressed by the cell that may relate to lysis other than B cell.For example, Btk is by mast cell-expressed
And the mast cell of Btk deficiency derived from bone marrow show impaired antigen temptation particle (Iwaki etc.,
J.Biol.Chem.2005,280：40261).This display Btk can such as become effective for treatment pathologic mast cells reaction
State is reacted and asthma.In addition, the monocyte from the XLA patient for wherein lacking Btk activity shows the TNF of reduction after stimulation
α generations (Horwood etc., J.Exp.Med.2003,197：1603).Therefore, the inflammation that TNF α mediates can be by the small molecule of Btk
Inhibitor inhibits.(Islam and Smith, Immunol moreover it has been reported that Btk plays a role in Apoptosis
Rev.2000,178：49), and therefore Btk inhibitor will be effective for treating certain B cell lymphomas and leukaemia
(Feldhah etc., J.Exp.Med.2005,201：1837).
On June 16th, 2012, Pharmacyclics biopharmaceutical companys disclose bruton's tyrosine kinase (Btk) suppression
Preparation Ibrutinib (PCI-32765) is for treating chronic lymphocytic leukemia/set lymphocytic lympboma (CLL/MCL)
2 newest Ib/II phases clinical trial results (PCYC-1102 and PCYC-1108).The experimental results showed that：In 61 recurrence/hardly possiblies
The property controlled and 31 did not received have high activity and well-tolerated in the CLL patients for the treatment of, and did not had patient during testing
It is discontinued because of adverse events.
Obviously, the outstanding clinical test results of Ibrutinib declare publicly the highly selective micromolecular inhibitor general of Btk kinases
The another hot spot in global new drug development field can be become.
The present invention provides a kind of composition containing formula (I) compound or its pharmaceutically acceptable salt.The formula (I) is changed
Conjunction object is disclosed in for information about in Chinese patent CN201410191608.Verified formula (I) compound or its pharmaceutically may be used
The salt of receiving can be used as Btk inhibitor and inhibit the relevant diseases such as chronic lymphocytic leukemia, but its solubility is low, permeability
It is larger to prepare oral solid formulation difficulty for difference.The present composition is to be directed to formula (I) compound or its pharmaceutically acceptable salt
Property feature and design, said preparation dissolution rate is good, stable quality, can meet clinical application demand, improves patient's compliance etc.
Requirements.
Invention content
The present invention provides a kind of composition and preparation method thereof containing formula (I) compound or its pharmaceutically acceptable salt,
The composition contains formula (I) compound or its pharmaceutically acceptable salt and its pharmaceutically acceptable excipient, described group
Capsule can directly be filled and capsule is made by filling capsule or powder after dry granulation by closing object, can also be pressed after dry granulation
Tablet, preferably capsule, more preferably dry granulation process is made in piece or direct powder compression.
Active constituent is that formula (I) compound or its pharmaceutically acceptable salt, weight account for group in Pharmaceutical composition of the present invention
The 10-70% for closing object fills capsule wherein after dry granulation or the preferred 30-60% of tabletting, powder directly fills capsule or tabletting
It is preferred that 20-50%.
Active constituent formula (I) compound or its pharmaceutically acceptable salt particle size range are that D50 is not more than 50 μm,
D90 is not more than 100 μm, and preferably D50 is not more than 25 μm, and D90 is not more than 50 μm.
Excipient in Pharmaceutical composition of the present invention includes filler, disintegrant, solubilizer, glidant and lubricant.
The filler is microcrystalline cellulose, Optimization-type microcrystalline cellulose (containing 2.0% superfine silica gel powder), starch, pregelatinated
The mixture of one or more of starch and lactose, preferably microcrystalline cellulose and Optimization-type microcrystalline cellulose (contain 2.0%
Superfine silica gel powder).
The disintegrant is crospovidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl fiber
The mixture of one or more of plain sodium, weight account for the 5-15% of composition.
The solubilizer is the mixture of one or more of lauryl sodium sulfate, poloxamer, polysorbate,
Weight accounts for the 1-10% of composition.
The glidant is silica, colloidal silicon dioxide, the mixture of one or more of talcum powder, weight
Account for the 0-2% of composition.
The lubricant is magnesium stearate, stearic acid, calcium stearate, talcum powder, hydrogenated vegetable oil, polyethylene glycol, tristearin
The mixture of one or more of fumaric acid sodium, Compritol 888 ATO, weight account for the 0.1-3% of composition quality, preferably
0.5-1.5%.
Pharmaceutical composition of the present invention can be prepared by following technique：
Dry granulation process：Filler, disintegrant, solubilizer, glidant and lubricant is added to formula (I) compound, mixes
It closes uniform；Powder after mixing is placed in dry granulating machine granulation, particle and pressed powder after granulation or capsule is taken to fill out
It fills, tablet can be with film coating.The parameter area of wherein dry granulation is as follows：
| Parameter | Range |
| Feeding frequency/Hz | 10-40 |
| Tabletting frequency/Hz | 10-40 |
| Pelletize frequency/Hz | 10-30 |
| Oil pressure/kg/m2 | 25-55 |
| Sieve/mm | 0.8-1.2 |
Direct powder compression or capsule fill process：Filler is added to formula (I) compound, disintegrant, solubilizer, helps stream
Agent and lubricant, tabletting or capsule filling after mixing, tablet can be with film coating.
Description of the drawings
Fig. 1 shows stripping curve of the capsule of embodiment 1,3,5,7,9 and 11 in 0.15% lauryl sodium sulfate.
Fig. 2 shows stripping curve of the tablet of embodiment 2,4,6,8,10 and 12 in 0.15% lauryl sodium sulfate.
Fig. 3 shows the capsule of embodiment 1 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Fig. 4 shows the tablet of embodiment 2 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Fig. 5 shows the capsule of embodiment 3 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Fig. 6 shows the tablet of embodiment 4 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Fig. 7 shows the capsule of embodiment 5 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Fig. 8 shows the tablet of embodiment 6 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Fig. 9 shows the capsule of embodiment 7 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Figure 10 shows the tablet of embodiment 8 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Figure 11 shows the capsule of embodiment 9 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
Stripping curve.
Figure 12 shows the tablet of embodiment 10 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
In stripping curve.
Figure 13 shows the capsule of embodiment 11 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
In stripping curve.
Figure 14 shows the tablet of embodiment 12 and its places 30 days under three conditions in 0.15% lauryl sodium sulfate
In stripping curve.
Specific implementation mode
It further illustrates the present invention by the following examples, but not as limitation of the present invention.
Examples 1 to 2
The pharmaceutical composition of the present invention, preferred formula composition are as follows：
| Supplementary material | Ratio (unit：%) |
| Formula (I) compound | 32.3 |
| Microcrystalline cellulose PH102 | 52.2 |
| Croscarmellose sodium | 12 |
| Lauryl sodium sulfate | 2.0 |
| Silica | 0.5 |
| Magnesium stearate | 1.0 |
| Summation | 100.0 |
Wherein formula (I) compound grain size D50 is 7.045 μm, and D90 is 36.176 μm.
Preparation method：By formula (I) compound, microcrystalline cellulose PH102, croscarmellose sodium, dodecyl sulphur
Sour sodium, silica and magnesium stearate are uniformly mixed, and GL2-25 types dry granulating machine is added, and (Zhangjagang City, which starts machine-building, to be had
Limit company) hopper granulation, grain made parameter is：Feeding frequency 12Hz, tabletting frequency 25Hz, pelletize frequency 20Hz, and oil pressure 30~
40kg/m2, sieve 1.0mm.Particle and powder filled capsule (embodiment 1) obtained are taken, or uses suitable mold tabletting
(embodiment 2).
Embodiment 3~4
The pharmaceutical composition of the present invention, preferred formula composition are as follows：
Wherein formula (I) compound grain size D50 is 7.865 μm, and D90 is 28.180 μm.
Preparation method：By formula (I) compound, microcrystalline cellulose PH102, sodium carboxymethyl starch, lauryl sodium sulfate, two
Silica and magnesium stearate are uniformly mixed, and the granulation of dry granulating machine hopper is added, and grain made parameter is：Feeding frequency 15Hz, tabletting
Frequency 30Hz, pelletize frequency 25Hz, 30~40kg/m of oil pressure2, sieve 0.8mm.
Particle and powder filled capsule (embodiment 3) obtained are taken, or uses suitable mold tabletting (embodiment 4).
Embodiment 5~6
The pharmaceutical composition of the present invention, preferred formula composition are as follows：
| Supplementary material | Ratio (unit：%) |
| Formula (I) compound | 60.0 |
| Microcrystalline cellulose PH102 | 22.5 |
| Crospovidone | 9.0 |
| Poloxamer | 7.0 |
| Silica | 0.5 |
| Magnesium stearate | 1.0 |
| Summation | 100.0 |
Wherein formula (I) compound grain size D50 is 3.272 μm, and D90 is 7.182 μm.
Preparation method：By formula (I) compound, microcrystalline cellulose PH102, crospovidone, poloxamer, silica and
Magnesium stearate is uniformly mixed, and the granulation of dry granulating machine hopper is added, and grain made parameter is：Feeding frequency 20Hz, tabletting frequency 40Hz,
Pelletize frequency 30Hz, 30~40kg/m of oil pressure2, sieve 1.2mm.Particle and powder filled capsule (embodiment 5) obtained are taken, or
Person uses suitable mold tabletting (embodiment 6).
Embodiment 7~8
The pharmaceutical composition of the present invention, preferred formula composition are as follows：
| Supplementary material | Ratio (unit：%) |
| Formula (I) compound | 20.0 |
| Microcrystalline cellulose PH102 | 68.0 |
| Croscarmellose sodium | 7.0 |
| Lauryl sodium sulfate | 1.5 |
| Silica | 2.0 |
| Magnesium stearate | 1.5 |
| Summation | 100.0 |
Wherein formula (I) compound grain size D50 is 6.844 μm, and D90 is 39.799 μm.
Preparation method：By formula (I) compound, microcrystalline cellulose PH102, croscarmellose sodium, dodecyl sulphur
Sour sodium, silica and magnesium stearate are uniformly mixed, filling capsule (embodiment 7), or (are implemented using suitable mold tabletting
Example 8).
Embodiment 9~10
The pharmaceutical composition of the present invention, preferred formula composition are as follows：
| Supplementary material | Ratio (unit：%) |
| Formula (I) compound | 40.0 |
| Optimization-type microcrystalline cellulose (contains 2.0% superfine silica gel powder) | 46.5 |
| Sodium carboxymethyl starch | 7.0 |
| Poloxamer | 5.0 |
| Colloidal silicon dioxide | 1.0 |
| Magnesium stearate | 0.5 |
| Summation | 100.0 |
Wherein formula (I) compound grain size D50 is 12.033 μm, and D90 is 50.852 μm.
Preparation method：By formula (I) compound, Optimization-type microcrystalline cellulose (containing 2.0% superfine silica gel powder), carboxymethyl starch
Sodium, poloxamer, colloidal silicon dioxide and magnesium stearate are uniformly mixed, filling capsule (embodiment 9), or use suitable mould
Has tabletting (embodiment 10).
Embodiment 11~12
The pharmaceutical composition of the present invention, preferred formula composition are as follows：
Wherein formula (I) compound grain size D50 is 37.025 μm, and D90 is 80.862 μm.
Preparation method：Formula (I) compound, Optimization-type microcrystalline cellulose (containing 2.0% superfine silica gel powder), cross-linked carboxymethyl is fine
The plain sodium of dimension, poloxamer, colloidal silicon dioxide and magnesium stearate are uniformly mixed, filling capsule (embodiment 11), or are used and closed
Suitable mold tabletting (embodiment 12).
Experimental example 1
The measurement of stripping curve of the present invention.
Above-described embodiment sample is taken, using Chinese Pharmacopoeia version four in 2015, the second method of dissolution rate and drug release determination is examined
Examine stripping curve.
Capsule dissolving-out method is：Paddle method (sedimentation basket), 0.15% lauryl sodium sulfate aqueous solution, 900ml, 75rpm, 37
± 0.5 DEG C, sample time 10,15,30 minutes.Stripping curve is shown in attached drawing 1.
Tablet dissolving-out method is：Paddle method, 0.15% lauryl sodium sulfate aqueous solution, 900ml, 75rpm, 37 ± 0.5 DEG C,
Sample time 10,15,30 minutes.Stripping curve is shown in attached drawing 2.
Experimental example 2
Stability study of the present invention
By the sample of embodiment 1~12, it is respectively placed in 60 DEG C of high temperature, high humidity RH92.5% and illumination 4500 ± 500Lx rings
Under border, 30 days were placed in open condition, then HPLC methods is used to measure catabolite and content, using Chinese Pharmacopoeia 2015 years
Version four, the second method of dissolution rate and drug release determination are investigated stripping curve (specific dissolving-out method is with experimental example 1), are as a result seen attached
Fig. 3~14.
Experimental result can be seen that sample that embodiment 1~12 obtains in 60 DEG C of high temperature, high humidity RH75% and illumination 4500
Under the conditions of ± 500Lx, related substance does not all obviously increase, and content is not also substantially reduced, and stripping curve does not have significant change.
Claims (9)
1. a kind of Pharmaceutical composition, containing in formula (I) compound or its pharmaceutically acceptable salt and disintegrant, solubilizer
At least one, formula (I) compound accounts for the 10-70% of total formula weight percentage.
2. pharmaceutical composition as described in claim 1, wherein the formula (I) compound or its pharmaceutically acceptable salt account for and match
The mass percent of square gross weight is 20-60%.
3. such as pharmaceutical composition according to any one of claims 1 to 2, wherein the composition includes disintegrant, it is described to collapse
Solution agent be crospovidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, one kind in croscarmellose sodium or
Several mixtures.
4. Pharmaceutical composition as claimed in claim 3, wherein the disintegrant is croscarmellose sodium, weight accounts for
The 5-15% of composition.
5. pharmaceutical composition as described in any one of claims 1 to 4, wherein the composition includes solubilizer, the increasing
Solvent is the mixture of one or more of lauryl sodium sulfate, poloxamer, polysorbate.
6. Pharmaceutical composition as claimed in claim 5, wherein the solubilizer is lauryl sodium sulfate, weight accounts for combination
The 1-10% of object.
7. such as pharmaceutical composition according to any one of claims 1 to 6, wherein the particle size range of the formula (I) compound is
D50 is not more than 50 μm, and D90 is not more than 100 μm.
8. such as pharmaceutical composition according to any one of claims 1 to 6, wherein the particle size range of the formula (I) compound is
D50 is not more than 25 μm, and D90 is not more than 50 μm.
9. the pharmaceutical composition as described in any one of claim 1-8, straight by capsule filling or powder after dry granulation
It connects capsule filling and hard capsule is made, it can also be after dry granulation tabletting or tablet is made in direct powder compression.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024083184A1 (en) * | 2022-10-20 | 2024-04-25 | 西藏海思科制药有限公司 | Pharmaceutical composition comprising egfr inhibitor |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104523695A (en) * | 2014-11-12 | 2015-04-22 | 广东东阳光药业有限公司 | Pharmaceutical composition for treating excessive proliferation diseases |
| CN104736178A (en) * | 2012-06-04 | 2015-06-24 | 药品循环公司 | Crystalline forms of a Bruton's tyrosine kinase inhibitor |
| CN105085474A (en) * | 2014-05-07 | 2015-11-25 | 北京赛林泰医药技术有限公司 | Bruton tyrosine kinase inhibitor |
| US20160287594A1 (en) * | 2015-04-06 | 2016-10-06 | Janssen Pharmaceutical Nv | Compositions Containing Ibrutinib |
| CN107427498A (en) * | 2015-03-03 | 2017-12-01 | 药品循环有限责任公司 | The medical formulation of bruton's tyrosine kinase inhibitor |
-
2017
- 2017-04-01 CN CN201710211095.5A patent/CN108653231A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104736178A (en) * | 2012-06-04 | 2015-06-24 | 药品循环公司 | Crystalline forms of a Bruton's tyrosine kinase inhibitor |
| CN105085474A (en) * | 2014-05-07 | 2015-11-25 | 北京赛林泰医药技术有限公司 | Bruton tyrosine kinase inhibitor |
| CN104523695A (en) * | 2014-11-12 | 2015-04-22 | 广东东阳光药业有限公司 | Pharmaceutical composition for treating excessive proliferation diseases |
| CN107427498A (en) * | 2015-03-03 | 2017-12-01 | 药品循环有限责任公司 | The medical formulation of bruton's tyrosine kinase inhibitor |
| US20160287594A1 (en) * | 2015-04-06 | 2016-10-06 | Janssen Pharmaceutical Nv | Compositions Containing Ibrutinib |
| CN107530293A (en) * | 2015-04-06 | 2018-01-02 | 詹森药业有限公司 | Include the composition that Buddhist nun is replaced according to Shandong |
Non-Patent Citations (1)
| Title |
|---|
| 安日明，: ""依鲁替尼胶囊处方的筛选研究"", 《安徽化工》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024083184A1 (en) * | 2022-10-20 | 2024-04-25 | 西藏海思科制药有限公司 | Pharmaceutical composition comprising egfr inhibitor |
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