CN103110597B - Erlotinib Hydrochloride piece and preparation method thereof - Google Patents
Erlotinib Hydrochloride piece and preparation method thereof Download PDFInfo
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- CN103110597B CN103110597B CN201310051789.9A CN201310051789A CN103110597B CN 103110597 B CN103110597 B CN 103110597B CN 201310051789 A CN201310051789 A CN 201310051789A CN 103110597 B CN103110597 B CN 103110597B
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- erlotinib hydrochloride
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Abstract
The invention discloses a kind of erlotinib Hydrochloride piece, contains surfactant of the HLB value between 10 to 20 as solubilizer, can effectively facilitate drug-eluting, the invention further relates to the preparation method of the tablet, its technical process is simple, good without particular/special requirement, product dissolution to raw material particle size.
Description
Technical field
The present invention relates to a kind of preparation method containing erlotinib Hydrochloride tablet.
Background technology
Erlotinib Hydrochloride piece is a kind of small molecule anti-cancer drug that Genentech, Roche and Osi Pharm Inc. develop jointly
Thing, trade name " Tarceva " (Erlotinib).In November, 2004 and, in September, 2005 was examined by U.S. FDA and Europe EMEA,
In the country's listing of seven, 80, the whole world.It is that a kind of EGF-R ELISA-tyrosine kinase (EGFR-TK) suppresses
Agent, is a small molecule oral drugs, it can be prevented by suppressing the tyrosine kinase activity of human epidermal growth factor acceptor -1
The intracellular signaling pathways of this receptor mediation, thus prevent growth of tumour cell and antitumor action are finally presented.
The molecular formula of Tarceva is C22H23N3O4, molecular weight 589.7, has following structural formula, its medicinal forms leads to
Often it is hydrochloride form.
The solubility of erlotinib Hydrochloride is set forth in patent CN100506803C.Crystal form A and crystal form B are in pH=
In 1 solution, balanced at 20 DEG C after twenty minutes, solubility only has 0.017% and 0.003%.Erlotinib Hydrochloride solubility property
It is not good enough, therefore original grinds piece and needs to add lauryl sodium sulfate in prescription, to improve the solubility of medicine and rate of dissolution.
But after inventor in prescription in practice, it has been found that with the addition of SDS, it is still necessary to which medicine is sufficiently micronized
Processing, can be effectively promoted drug-eluting.Generally, the granularity D90 of erlotinib Hydrochloride raw material is required to be less than 10 μm, i.e.,
The particle diameter of at least more than 90% drug microparticles is less than 10 μm, granularity can usually be examined using laser particle analyzer
Survey.
Sufficiently fine erlotinib Hydrochloride in order to obtain, is industrially usually realized in a manner of air-flow crushing, this can be obvious
Increase medicine production cost, while add the exposure probability of medicine, since erlotinib Hydrochloride is antitumor drug, tool
There is larger toxic side effect, this can have a negative impact the health of direct labor.Drug microparticles superfine at the same time also can
Difficulty, such as the dust from flying of electrostatic of bigger or more are caused to industrial production, will also result in the unfavorable shadow such as mixing efficiency difference
Ring.
Therefore seek a kind of less harsh to the requirement of drug particles degree, can simplify the prescription of production technology and preparation method is
It is highly desirable.
The content of the invention
The present invention provides a kind of erlotinib Hydrochloride piece, the surfactant containing HLB value between 10~20.Inventor
Find under study for action, if adding surfactant of the HLB value between 10~20 in prescription, the molten of medicine can be effectively promoted
Go out, even if the granularity of medicine is bigger, such as raw material particle size D90Between 20-50 μm, medicine can also have faster dissolution speed
Degree.For the lauryl sodium sulfate of HLB=40, surfactant of the HLB value between 10~20 has
The hydrophilic and oleophilic performance more balanced, can more effectively improve the surface nature of erlotinib Hydrochloride, so as to improve the molten of medicine
Go out speed, increase solubility.And then the dissolution rate for making pharmaceutical preparation is faster, helps to improve drug bioavailability.
, according to the invention it is preferred to surfactant of the HLB value between 12~18, more preferably HLB value is between 13~16
Surfactant.
According to the present invention, the application example of surfactant is selected from tween or Crodaret.
According to the present invention, surfactant is preferably polysorbas20, polysorbate40,40 hydrogenated castor of polysorbate60 or polyoxyethylene
Oil.Wherein, polyoxyl 40 hydrogenated castor oil is called polyoxyethylene stearate (40) ester for 2010 editions in Chinese Pharmacopoeia.
Crodaret may be selected from trade nameThe product of RH40, its manufacturer are Germany
BASF AG.
According to the present invention, active ingredient hydrochloric acid Tarceva is preferably crystal form A or crystal form B, it has attached drawing 1 or attached respectively
X-ray diffracting spectrum shown in Fig. 2.
Erlotinib Hydrochloride piece according to the present invention, contains pharmaceutically acceptable additive.
According to the present invention, additive includes filler, selects microcrystalline cellulose, powdered cellulose, calcium monohydrogen phosphate, optimizes micro-
Crystalline cellulose, starch etc..
According to the present invention, additive includes disintegrant, selected from crospovidone, Ac-Di-Sol, low substitution
Hydroxypropyl cellulose, sodium carboxymethyl starch etc..
According to the present invention, additive includes lubricant, selected from magnesium stearate, sodium stearyl fumarate etc..
The present invention also provides the preparation method of the erlotinib Hydrochloride piece, comprise the following steps：
A) surfactant by erlotinib Hydrochloride and HLB value between 10~20, and other are pharmaceutically acceptable
Additive mixes；
B) mixture of previous step is prepared into particle by dry granulation process；
C) it is tabletted after particle adds mix lubricant.
Brief description of the drawings：
Attached drawing 1 is the X-ray diffracting spectrum of crystal form A erlotinib Hydrochlorides；
Attached drawing 2 is the X-ray diffracting spectrum of crystal form B erlotinib Hydrochlorides.
Specific embodiment
Embodiment 1-4 and comparative example 5,6
Table 1
Preparation process：
1st, willRH40 (or polysorbas20, polysorbate40, SDS) and lactose mixing；
2nd, the material in addition to magnesium stearate is mixed with the mixture that step " 1 " obtains；
3rd, the material obtained by step " 2 " is subjected to non-slurry pelletizing；
4th, magnesium stearate mixing is added, and it is tabletted；
5th, slice, thin piece is coated using the coating powder of trade name Opadry.
The slice, thin piece prepared to embodiment 1~6, carries out the detection of stripping curve, detection method is：Dissolution medium volume：
1000ml, dissolution medium be pH1.0+1%SDS hydrochloric acid solution, rotating speed 75rpm, paddle method.Stripping curve the results are shown in Table 2.
Table 2
Comparing embodiment 1 and comparative example 5, its use are tested with a collection of medicine, it can be found that
RH40 can effectively facilitate the dissolution of medicine.
Comparing embodiment 1~4 and comparative example 6, it can be found that usingRH40, polysorbas20, polysorbate40
When, it is also faster than using 6 dissolution of embodiment of fine granularity medicine even with the medicine of coarseness.
40 DEG C are carried out to embodiment 1, the accelerated test of 75% humidity is investigated, and as a result see the table below：
Claims (9)
1. a kind of erlotinib Hydrochloride piece, contains surfactant, it is characterised in that the HLB value of surfactant 10-20 it
Between.
2. erlotinib Hydrochloride piece as claimed in claim 1, it is characterised in that the HLB value of surfactant is between 12-18.
3. erlotinib Hydrochloride piece as claimed in claim 2, it is characterised in that the HLB value of surfactant is between 13-16.
4. erlotinib Hydrochloride piece as claimed in claim 2, it is characterised in that surfactant is selected from polyethylene glycol hydrogenated castor
Sesame oil, polysorbas20, polysorbate40, the one or more in polysorbate60.
5. erlotinib Hydrochloride piece as claimed in claim 4, it is characterised in that surfactant is selected from polyethylene glycol hydrogenated castor
Sesame oil.
6. erlotinib Hydrochloride piece as claimed in claim 5, it is characterised in that surfactant is hydrogenated selected from polyoxyethylene 40
Castor oil.
7. erlotinib Hydrochloride piece as claimed in claim 1, it is characterised in that part by weight of the surfactant in prescription
For 0.25-5%.
8. erlotinib Hydrochloride piece as claimed in claim 7, it is characterised in that part by weight of the surfactant in prescription
For 1-2.5%.
9. prepare the method for erlotinib Hydrochloride piece as claimed in claim 1, containing having the following steps：
A) surfactant by erlotinib Hydrochloride and HLB value between 10~20, and other pharmaceutically acceptable additions
Agent mixes；
B) mixture of previous step is prepared into particle by dry granulation process；
C) it is tabletted after particle adds mix lubricant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310051789.9A CN103110597B (en) | 2013-02-02 | 2013-02-02 | Erlotinib Hydrochloride piece and preparation method thereof |
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| CN201310051789.9A CN103110597B (en) | 2013-02-02 | 2013-02-02 | Erlotinib Hydrochloride piece and preparation method thereof |
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| Publication Number | Publication Date |
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| CN103110597A CN103110597A (en) | 2013-05-22 |
| CN103110597B true CN103110597B (en) | 2018-04-13 |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103705477A (en) * | 2013-12-26 | 2014-04-09 | 山东博迈康药物研究有限公司 | Tablets containing erlotinib hydrochloride and preparation method thereof |
| CN105362239A (en) * | 2014-09-01 | 2016-03-02 | 深圳信立泰药业股份有限公司 | Medicine composition containing erlotinib hydrochloride and preparation method of medicine composition |
| CN105616374A (en) * | 2014-11-05 | 2016-06-01 | 四川科伦药物研究院有限公司 | Erlotinib hydrochloride tablet and preparation method thereof |
| CN107961224B (en) * | 2017-12-06 | 2021-05-04 | 齐鲁制药(海南)有限公司 | Acertinib tablet and preparation method thereof |
| CN109602715A (en) * | 2019-02-21 | 2019-04-12 | 江苏豪森药业集团有限公司 | Erlotinib Hydrochloride tablet and preparation method thereof |
| CN116251186A (en) * | 2021-12-09 | 2023-06-13 | 成都瑞沐生物医药科技有限公司 | Tyrosine kinase inhibitor ophthalmic preparation and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009025875A1 (en) * | 2007-08-23 | 2009-02-26 | Plus Chemicals Sa | Stable formulations of crystalline erlotinib hcl |
| CN102048737A (en) * | 2009-10-28 | 2011-05-11 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treating tumor diseases |
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2013
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009025875A1 (en) * | 2007-08-23 | 2009-02-26 | Plus Chemicals Sa | Stable formulations of crystalline erlotinib hcl |
| CN102048737A (en) * | 2009-10-28 | 2011-05-11 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treating tumor diseases |
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Effective date of registration: 20181203 Address after: 317024 Flood Bridge, Linhai City, Zhejiang Province Co-patentee after: Universal Bailey biological medicine research and development (Shanghai) Co., Ltd. Patentee after: Zhejiang Huahai Pharmaceutical Co., Ltd. Address before: 317024 Xunqiao Development Zone, Linhai City, Zhejiang Province Patentee before: Zhejiang Huahai Pharmaceutical Co., Ltd. |
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