CN103349655A - Tamoxifen citrate enteric capsules - Google Patents
Tamoxifen citrate enteric capsules Download PDFInfo
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- CN103349655A CN103349655A CN2013103079684A CN201310307968A CN103349655A CN 103349655 A CN103349655 A CN 103349655A CN 2013103079684 A CN2013103079684 A CN 2013103079684A CN 201310307968 A CN201310307968 A CN 201310307968A CN 103349655 A CN103349655 A CN 103349655A
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- tamoxifen citrate
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Abstract
The invention relates to tamoxifen citrate clathrate compound enteric capsules, the preparation method of which comprises the steps of preparing tamoxifen citrates into clathrate compounds and further preparing the clathrate compounds into the enteric capsules.
Description
Technical field
The application relates to a kind of enteric coated capsule, particularly, is Tamoxifen Citrate clathrate enteric coated capsule.
Background technology
Tamoxifen (tamoxifen, TAM) is a kind of nonsteroidal complex, and 1977 by the treatment of U.S. food medication management committee approval for postmenopausal women's metastatic breast cancer.Through nearly 30 years applicating history, the existing generation that also is used for Breast Cancer Prevention.TAM belongs to first generation selective estrogen receptor modulators (selective estrogen receptor modulators, SERMs), have estrogen excitement and the estrogenic dual function of antagonism, different kind systems, tissue and gene expression type are depended in this effect, at different target organs or target cell different effects are arranged.As producing the estrogenic effect of antagonism at mammary gland tissue TAM, then produce the estrogen agonism in uterus and osseous tissue.TAM by and estrogen competition target cell kytoplasm in estrogen receptor (estrogen receptor, ER), form complex, enter karyon, the internal energy ER of being combined with estrogen of kytoplasm is reduced, and the time that this complex stays in the karyon storage is longer, and kytoplasm ER has no way of replenishing, cause cytosol receptor to reduce, exhaust, finally show as lasting estrogen antagonism.
Estrogen inhibitor Tamoxifen Citrate is used for the treatment of all kinds of breast carcinoma, is particularly useful for the lower Postmenopausal Breast Cancer women patient of estrogen receptor and the progesterone receptor positive and prostate specific antigen level.This medicine not only can be postponed breast cancer relapse or be prolonged patient's survival period, and can significantly reduce the danger that side breast carcinoma occurs, and side effect is very few.
Tamoxifen Citrate mainly contains the dosage forms such as tablet, capsule, injection at present for clinical, and these dosage forms are relatively poor at the gastrointestinal tract dissolution, and bioavailability is not high.CN1389199A discloses a kind of slow-releasing Tamoxifen citrate tablet, and CN1654037A discloses a kind of Tamoxifen Citrate dispersible tablet.Yet this preparation cost is high, bioavailability is low, can not be advantageously applied to clinical.
Summary of the invention
The present invention has invented Tamoxifen Citrate clathrate enteric coated capsule in order to solve the existing low shortcoming of Tamoxifen Citrate preparation bioavailability.
Clathrate has the following advantages: cover bad stink, reduce zest; Increase drug dissolution and bioavailability; Improve medicine stability.
The applicant finds, now Tamoxifen Citrate is prepared into clathrate, is prepared into enteric coated capsule in conjunction with specific adjuvant again, has advantages of that stability is high, disintegration rate is fast and bioavailability is high.
The application provides a kind of enteric coated capsule of Tamoxifen Citrate, comprising:
23 parts of Tamoxifen Citrate clathrates
21 parts of diluent
26 parts of lubricants
3 parts of enteric coating materials
In this application, select specific adjuvant to prepare Tamoxifen Citrate clathrate enteric coated capsule.Wherein said diluent is the compositions of glucose and mannitol, the two part by weight is 7.3:2.7, lubricant is polyvinylpolypyrrolidone and talcous compositions, the two part by weight is 1:3.3, enteric coating material is the compositions of HP-55 and CAP, and the two part by weight is 1:2.6.Experimental results show that, be not that the conventional adjuvant of any pharmacy all is fit to preparation Tamoxifen Citrate clathrate enteric coated capsule, the effect of Tamoxifen Citrate clathrate enteric coated capsule at aspects such as dissolution velocity, stability, dissolutions of selecting this specific adjuvant to prepare is better than the Tamoxifen Citrate clathrate enteric coated capsule that other adjuvants prepare far away.
The Tamoxifen Citrate clathrate comprises active component and enclose material, and active component is Tamoxifen Citrate, and the enclose material is alpha-cyclodextrin.The part by weight of active component and enclose material is 2:7.Experiment showed, beta-schardinger dextrin-, the clathrate that the Tamoxifen Citrate clathrate that hydroxyl beta-schardinger dextrin-, hydroxypropylβ-cyclodextrin prepare prepares inferior to alpha-cyclodextrin in aspect effects such as disintegration rate, stability, dissolutions far away.
Different enclose materials are on the impact of Tamoxifen Citrate clathrate
Test method is with reference to the method for two regulations of 2010 editions Chinese Pharmacopoeias.
The preparation method of Tamoxifen Citrate clathrate comprises:
(1) in water or aquiferous ethanol medium, by a certain percentage, with Tamoxifen Citrate and alpha-cyclodextrin reaction, gained solution through extremely clarification of filtering with microporous membrane, is isolated clathrate from mixture; Or
(2) with solid form, with Tamoxifen Citrate and alpha-cyclodextrin reaction; Or
(3) high energy milling is carried out in the reaction of Tamoxifen Citrate and alpha-cyclodextrin.
Metering of the present invention is weight.
The prescription of Tamoxifen Citrate enteric coated capsule of the present invention is (by weight):
23 parts of Tamoxifen Citrate clathrates
The compositions of glucose and mannitol
(the two part by weight is 7.3:2.7) 21 parts
Polyvinylpolypyrrolidone and talcous compositions
(the two part by weight is 1:3.3) 26 parts
The compositions of HP-55 and CAP
(the two part by weight is 1:2.6) 3 parts
The preparation method of capsule: the Tamoxifen Citrate clathrate was pulverized 100 mesh sieves, all the other adjuvants were pulverized 80 mesh sieves; Accurately take by weighing the supplementary material of recipe quantity, mix homogeneously adds suitable quantity of water mixture furnishing paste is granulated at granulator, 18 mesh sieve granulate, and 60 ℃ of dryings get final product the granule that the makes hungry area softgel shell of packing into.
Embodiment 1 prescription
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 2:7
23 parts of Tamoxifen Citrate clathrates
21 parts of the compositionss of glucose and mannitol (the two part by weight is 7.3:2.7)
26 parts of polyvinylpolypyrrolidone and talcous compositionss (the two part by weight is 1:3.3)
The compositions of HP-55 and CAP
(the two part by weight is 1:2.6) 3 parts
Preparation method:
1. prepare by the following method the Tamoxifen Citrate clathrate:
(1) in water or aquiferous ethanol medium, by a certain percentage, with Tamoxifen Citrate and alpha-cyclodextrin reaction, gained solution through extremely clarification of filtering with microporous membrane, is isolated clathrate from mixture; Or
(2) with solid form, with Tamoxifen Citrate and alpha-cyclodextrin reaction; Or
(3) high energy milling is carried out in the reaction of Tamoxifen Citrate and alpha-cyclodextrin.
2. the Tamoxifen Citrate clathrate was pulverized 100 mesh sieves, all the other adjuvants were pulverized 80 mesh sieves; Accurately take by weighing the supplementary material of recipe quantity, mix homogeneously adds suitable quantity of water mixture furnishing paste is granulated at granulator, 18 mesh sieve granulate, and 60 ℃ of dryings get final product the granule that the makes hungry area softgel shell of packing into.
Embodiment 2
Embodiment 1 described Tamoxifen Citrate and alpha-cyclodextrin fully be ground in 50% ethanol form even mastic, behind vacuum drying white powder, in the water of this powder solubility property more not the Tamoxifen Citrate of enclose improved 12 times.
The comparative example 1
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 2:7
23 parts of Tamoxifen Citrate clathrates
21 parts of the compositionss of glucose and mannitol (the two part by weight is 1:1)
26 parts of polyvinylpolypyrrolidone and talcous compositionss (the two part by weight is 1:3.3)
The compositions of HP-55 and CAP
(the two part by weight is 1:2.6) 3 parts
Preparation method is the same.
The comparative example 2
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 2:7
23 parts of Tamoxifen Citrate clathrates
21 parts of the compositionss of glucose and mannitol (the two part by weight is 7.3:2.7)
26 parts of polyvinylpolypyrrolidone and talcous compositionss (the two part by weight is 1:1)
The compositions of HP-55 and CAP
(the two part by weight is 1:2.6) 3 parts
Preparation method is the same.
The comparative example 3
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 2:7
23 parts of Tamoxifen Citrate clathrates
21 parts of starch
26 parts of polyvinylpolypyrrolidone and talcous compositionss (the two part by weight is 1:3.3)
The compositions of HP-55 and CAP
(the two part by weight is 1:2.6) 3 parts
Preparation method is the same.
The comparative example 4
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 2:7
23 parts of Tamoxifen Citrate clathrates
21 parts of the compositionss of glucose and mannitol (the two part by weight is 7.3:2.7)
26 parts of polyvinylpolypyrrolidone
The compositions of HP-55 and CAP
(the two part by weight is 1:2.6) 3 parts
Preparation method is the same.
The comparative example 5
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 2:7
23 parts of Tamoxifen Citrate clathrates
21 parts of the compositionss of Fructus Vitis viniferae sugar and starch (the two part by weight is 7.3:2.7)
26 parts of Pulvis Talci
The compositions of HP-55 and CAP
(the two part by weight is 1:2.6) 3 parts
Preparation method is the same.
The comparative example 6
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 2:7
23 parts of Tamoxifen Citrate clathrates
21 parts of glucoses
26 parts of micropowder silica gels
The compositions of HP-55 and CAP
(the two part by weight is 1:2.6) 3 parts
Preparation method is the same.
Different enteric coating materials are on the impact of Tamoxifen Citrate enteric coated capsule
Test method: the Tamoxifen Citrate enteric coated capsule that different enteric coating materials prepare is measured dissolution rate respectively in simulated gastric fluid environment and simulation intestinal environment.The results are shown in Table 1.
Prescription:
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 1:2
23 parts of Tamoxifen Citrate clathrates
21 parts of the compositionss of glucose and mannitol (the two part by weight is 7.3:2.7)
26 parts of polyvinylpolypyrrolidone and talcous compositionss (the two part by weight is 1:3.3)
3 parts of enteric coating materials
Table 1
Can be found out by table 1 data, only have and adopt the compositions (the two part by weight is 1:2.6) of HP-55 and CAP almost insoluble in the simulated gastric fluid environment as group 1 enteric coated capsule (being embodiment 1) of enteric coating material, almost all strippings in the simulation intestinal environment; And the enteric coated capsule that other enteric coating materials prepare dissolution rate in the simulated gastric fluid environment is larger, can not make capsule safety stomach and to again disintegrate of intestinal.Therefore, what the application's enteric coated capsule adopted is specific enteric coating adjuvant, and the enteric coating adjuvant of other types is not suitable for being prepared into Tamoxifen Citrate clathrate enteric coated capsule.
Tamoxifen Citrate enteric coated capsule stability test
Outward appearance, dissolution, content and dissolution time to the enteric coated capsule of embodiment 1 and comparative example 1-6 have carried out factors influencing.
(1) hot test: get embodiment 1 and comparative example 1-6 sample is tiled in the culture dish in right amount, place 60 ℃ calorstat to place 10 days, during this 0th, 5,10 day, taking sample determination respectively, measurement result sees Table 2.
(2) high wet test: sample thief is tiled in the culture dish in right amount, under the condition of 25 ℃ of relative humidity RH90% ± 5%, placed 10 days, and during this 0th, 5,10 day, taking sample determination respectively, measurement result sees Table 2.
(3) strong illumination test, sample thief is tiled in the culture dish in right amount, places the light cupboard the condition illumination of 4500Lx ± 500Lx 10 days, and during this 0th, 5,10 day, taking sample determination respectively, measurement result sees Table 2.
Hot and humid and the high light stability inferior of each embodiment enteric coated capsule of table 2.
The diluent type of selecting among the comparative example 1 does not change, but the part by weight of the two changes in the compositions of glucose and mannitol, the lubricant type of selecting among the comparative example 2 does not change, but the part by weight of the two changes in polyvinylpolypyrrolidone and the talcous compositions, diluent changes to starch among the comparative example 3, comparative example's 4 lubricants change to single polyvinylpolypyrrolidone, lubricant changes to Pulvis Talci among the comparative example 5, diluent changes to glucose among the comparative example 6, and lubricant changes to micropowder silica gel.Experimental data by table 2 can be found out, in the identical situation of each composition consumption, no matter be that change has occured the adjuvant type, or the adjuvant type not have to change but has changed the usage ratio of component, and the stability of the Tamoxifen Citrate enteric coated capsule for preparing (comparative example 1-6), dissolution are with respect to all significantly reductions of embodiment 1.Above-mentioned description of test only has the described Tamoxifen Citrate enteric coated capsule that is prepared by specific adjuvant and specific consumption of the application just to have unforeseeable good dissolution velocity, stability, dissolution.
Claims (2)
1. capsule, wherein active component is Tamoxifen Citrate.
2. capsule as claimed in claim 1, wherein capsule is enteric coated capsule, and Tamoxifen Citrate is clathrate, and the enclose material is alpha-cyclodextrin, and the part by weight of etoposide and enclose material is 2:7, the enteric coated capsule prescription is, by weight:
23 parts of Tamoxifen Citrate clathrates
21 parts of the compositionss of glucose and mannitol (the two part by weight is 1:1)
26 parts of polyvinylpolypyrrolidone and talcous compositionss (the two part by weight is 1:3.3)
3 parts of the compositionss of HP-55 and CAP (the two part by weight is 1:2.6).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310307968.4A CN103349655B (en) | 2013-07-22 | 2013-07-22 | Tamoxifen citrate enteric capsules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310307968.4A CN103349655B (en) | 2013-07-22 | 2013-07-22 | Tamoxifen citrate enteric capsules |
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| Publication Number | Publication Date |
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| CN103349655A true CN103349655A (en) | 2013-10-16 |
| CN103349655B CN103349655B (en) | 2015-04-29 |
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| CN201310307968.4A Active CN103349655B (en) | 2013-07-22 | 2013-07-22 | Tamoxifen citrate enteric capsules |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101268050A (en) * | 2005-07-26 | 2008-09-17 | 尼科梅德有限责任公司 | Isotopically substituted pantoprazole |
| CN101269050A (en) * | 2008-05-21 | 2008-09-24 | 孙向阳 | Acidum citricum nolvadex capsule and preparation method thereof |
-
2013
- 2013-07-22 CN CN201310307968.4A patent/CN103349655B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101268050A (en) * | 2005-07-26 | 2008-09-17 | 尼科梅德有限责任公司 | Isotopically substituted pantoprazole |
| CN101269050A (en) * | 2008-05-21 | 2008-09-24 | 孙向阳 | Acidum citricum nolvadex capsule and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 潘小磊等: "环糊精纳米给药系统在药物传递中的应用", 《沈阳药科大学学报》, vol. 28, no. 8, 31 August 2011 (2011-08-31) * |
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| CN103349655B (en) | 2015-04-29 |
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