CN103349649B - Tamoxifen citrate dispersible tablets - Google Patents
Tamoxifen citrate dispersible tablets Download PDFInfo
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- CN103349649B CN103349649B CN201310309007.7A CN201310309007A CN103349649B CN 103349649 B CN103349649 B CN 103349649B CN 201310309007 A CN201310309007 A CN 201310309007A CN 103349649 B CN103349649 B CN 103349649B
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- tamoxifen citrate
- clathrate
- dispersible tablet
- cyclodextrin
- tamoxifen
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Abstract
The invention relates to tamoxifen citrate dispersible tablets, the preparation method of which comprises the steps of preparing tamoxifen citrates into clathrate compounds and further preparing the clathrate compounds into dispersible tablets.
Description
Technical field
The application relates to a kind of dispersible tablet, particularly, is Tamoxifen Citrate clathrate dispersible tablet.
Background technology
Tamoxifen (tamoxifen, TAM) is a kind of nonsteroidal complex, within 1977, is used for the treatment of postmenopausal women's metastatic breast cancer by the approval of U.S. food medication management committee.Through the applicating history of nearly 30 years, existing also for the generation of Breast Cancer Prevention.TAM belongs to first generation selective estrogen receptor modulators (selective estrogen receptor modulators, SERMs), there is the dual function of estrogen-agonistic and antagonising oestrogen, different germlines, tissue and gene expression pattern are depended in this effect, have different effects at different target organs or target cell.As the effect producing antagonising oestrogen at mammary gland tissue TAM, then produce estrogen-agonistic effect in uterus and osseous tissue.TAM is by competing estrogen receptor (the estrogen receptor in target cell cytoplasm with estrogen, ER), form complex, enter karyon, the ER that can be combined with estrogen in kytoplasm is reduced, and it is longer that this complex stores up at karyon the time stayed, and kytoplasm ER has no way of supplementing, cause cytosol receptor to reduce, exhaust, finally show as lasting estrogen antagonism effect.
Estrogen inhibitors Tamoxifen Citrate is used for the treatment of all kinds of breast carcinoma, is particularly useful for the Postmenopausal Breast Cancer women patient that estrogen receptor and progesterone receptor positive and prostate specific antigen level are lower.This medicine not only can be postponed breast cancer relapse or be extended the survival period of patient, and significantly can reduce the danger of side breast carcinoma generation, and side effect is very few.
Tamoxifen Citrate mainly contains the dosage forms such as tablet, capsule, injection at present for Clinical practice, and these dosage forms are poor at gastrointestinal tract dissolution, and bioavailability is not high.CN1389199A discloses a kind of slow-releasing Tamoxifen citrate tablet, but this preparation cost is high, bioavailability is low, can not be advantageously applied to clinical.
Dispersible tablet is put into after water can disintegrate rapidly, forms the ground suspension that is uniformly dispersed, has easy to use, the feature that bioavailability is high.The preparation method of dispersible tablet, working condition and production technology are simple, and instructions of taking is convenient, can swallow as conventional tablet, also can be distributed to wet suit and use.
Summary of the invention
The present invention, in order to solve the shortcoming that the onset of existing Tamoxifen Citrate preparation is slow, bioavailability is low, has invented Tamoxifen Citrate clathrate dispersible tablet.
Dispersible tablet is relative to conventional tablet, and in disintegrate medium, disintegration is less than 3 minutes, and the granule after disintegrate can all by No. 2 sieves, and compared with other types preparation, it is rapid that dispersible tablet has stripping, absorb fast, the advantages such as bioavailability is high, taking convenience.
Clathrate has the following advantages: cover bad stink, reduces zest; Increase drug dissolution and bioavailability; Improve medicine stability.
Tamoxifen Citrate is first prepared into clathrate by the application, and then prepared composition discrete piece, enclose and dispersion technology is united two into one, and plays the advantage of two aspects.
Tamoxifen Citrate clathrate comprises active component and enclose material, and active component is Tamoxifen Citrate, and enclose material is alpha-cyclodextrin.The part by weight of active component and enclose material is 1:2.Experiment prove, beta-schardinger dextrin-, hydroxyl beta-schardinger dextrin-, the Tamoxifen Citrate clathrate that hydroxypropylβ-cyclodextrin prepares in disintegration rate, stability, dissolution etc. effect far away inferior to the clathrate that alpha-cyclodextrin prepares.
Different enclose material is on the impact of Tamoxifen Citrate clathrate
Test method is with reference to the method for 2010 editions Chinese Pharmacopoeias two regulation.
The present invention also adopts the special adjuvant of dispersible tablet, and disintegrate is rapid, rapid-action.
The preparation method of Tamoxifen Citrate clathrate comprises:
(1) in water or aquiferous ethanol medium, by a certain percentage, Tamoxifen Citrate and alpha-cyclodextrin are reacted, by gained solution through filtering with microporous membrane extremely clarification, from mixture, isolate clathrate; Or
(2) in solid form, Tamoxifen Citrate and alpha-cyclodextrin are reacted; Or
(3) Tamoxifen Citrate and alpha-cyclodextrin react and carry out high energy milling.
Metering of the present invention is weight.
Described in the application, the prescription of Tamoxifen Citrate dispersible tablet is (by weight):
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 1:2
Adopt the preparation effect that can significantly improve dispersible tablet during the prescription of this specific proportioning, accelerate disintegration rate.
Embodiment 1
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 1:2
Preparation method:
1. prepare Tamoxifen Citrate clathrate by the following method:
(1) in water or aquiferous ethanol medium, by a certain percentage, Tamoxifen Citrate and alpha-cyclodextrin are reacted, by gained solution through filtering with microporous membrane extremely clarification, from mixture, isolate clathrate; Or
(2) in solid form, Tamoxifen Citrate and alpha-cyclodextrin are reacted; Or
(3) Tamoxifen Citrate and alpha-cyclodextrin react and carry out high energy milling.
2. by the low-substituted hydroxypropyl cellulose of recipe quantity, carboxymethyl starch sodium, sorbitol, after cyclamate is mixed homogeneously by the equivalent method of progressively increasing with Tamoxifen Citrate clathrate, then add magnesium stearate, micropowder silica gel, mixing, tabletting, obtains Tamoxifen Citrate clathrate dispersible tablet.
Comparative examples 1
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 1:2
Preparation method is the same
Comparative examples 2
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 1:2
Preparation method is the same
Comparative examples 3
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 1:2
Comparative examples 4
Tamoxifen Citrate clathrate: Tamoxifen Citrate: alpha-cyclodextrin is 1:2
The analytical test result of Tamoxifen Citrate clathrate dispersible tablet prepared by the above embodiment of the present invention:
(1) weight differential of the Tamoxifen Citrate clathrate dispersible tablet of embodiment 1 preparation is little, and unilateral bright and clean, hardness is moderate, and mouthfeel is good.Tamoxifen Citrate dispersible tablet weight differential prepared by comparative examples 1-4 is little, unilateral injustice, and hardness is little, and mouthfeel is slightly poor.
(2) Tamoxifen Citrate described in embodiment 1 and alpha-cyclodextrin are fully ground in 50% ethanol the even mastic of formation, after vacuum drying, obtain white powder, in the water of this powder, the Tamoxifen Citrate of the more non-enclose of solubility property improves 12 times.
(3) dispersing uniformity experimental result display: according to the method for 2010 editions Chinese Pharmacopoeias two regulation, Example 1 and each 6 of comparative examples 1-4, put in 250ml beaker, add the water 100ml of about 20 DEG C, jolting 90 seconds, the whole disintegrate of embodiment 1 dispersible tablet also passes through No. two sieves.100% is shortened than 3 minute time limit of States Pharmacopoeia specifications.Comparative examples 1-4 dispersible tablet jolting whole disintegrate by No. two sieves after 4 minutes.
(4) dissolution test result display: according to dissolution method (Chinese Pharmacopoeia 2010 editions two annex XC second methods), using 0.01mol/L hydrochloric acid solution 900ml as dissolution medium, rotating speed is 50 revs/min, operate in accordance with the law, every sheet stripping quantity is measured according to ultraviolet visible spectrophotometry, result be the stripping percentage rate of embodiment 1 dispersible tablet in 60 seconds about 90%, substantially all strippings in 90 seconds.Comparative examples 1-4 dispersible tablet after 3 minutes stripping percentage rate about 80%, basic all strippings in 5 minutes.The results are shown in following table 1.
Compared with embodiment 1, when each Ingredient Amount is identical, in comparative examples 1, the part by weight of disintegrating agent low-substituted hydroxypropyl cellulose and carboxymethyl starch sodium there occurs change, comparative examples 2 uses single low-substituted hydroxypropyl cellulose as disintegrating agent, and comparative examples 3 uses single carboxymethyl starch sodium as disintegrating agent.Comparative examples 4 is compared with embodiment 1, and each composition is identical, but consumption is different.
Result shows, Tamoxifen Citrate clathrate dispersible tablet provided by the invention meets the regulation of Chinese Pharmacopoeia (2000 editions) about dispersible tablet.The Tamoxifen Citrate clathrate dispersible tablet (comparative examples 1-4) that the Tamoxifen Citrate clathrate dispersible tablet (embodiment 1) selecting specific adjuvant and consumption to prepare is prepared compared to nonspecific adjuvant and consumption has unforeseeable excellent effect in outward appearance, disintegration and dissolution.
Claims (1)
1. a Tamoxifen Citrate dispersible tablet, wherein active component is Tamoxifen Citrate clathrate, and enclose material is alpha-cyclodextrin, and the part by weight of Tamoxifen Citrate and enclose material is 1:2, consisting of of described dispersible tablet, by weight:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310309007.7A CN103349649B (en) | 2013-07-22 | 2013-07-22 | Tamoxifen citrate dispersible tablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310309007.7A CN103349649B (en) | 2013-07-22 | 2013-07-22 | Tamoxifen citrate dispersible tablets |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103349649A CN103349649A (en) | 2013-10-16 |
| CN103349649B true CN103349649B (en) | 2015-02-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201310309007.7A Active CN103349649B (en) | 2013-07-22 | 2013-07-22 | Tamoxifen citrate dispersible tablets |
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Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1539411A (en) * | 2003-10-31 | 2004-10-27 | 沈阳药科大学 | Dispersion tablet of Tamoxifen(Nolvedox) of cedrat acid as well as preparationmethod and usage |
| CN1275593C (en) * | 2004-02-13 | 2006-09-20 | 马晶 | Dispersible tablet of tamoxifen citrate and preparation method thereof |
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