CN106309387A - Everolimus tablet - Google Patents
Everolimus tablet Download PDFInfo
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- CN106309387A CN106309387A CN201510404952.4A CN201510404952A CN106309387A CN 106309387 A CN106309387 A CN 106309387A CN 201510404952 A CN201510404952 A CN 201510404952A CN 106309387 A CN106309387 A CN 106309387A
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- everolimus
- tablet
- polyethylene glycol
- hydroxypropyl cellulose
- everolimus tablet
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to an everolimus tablet. The everolimus tablet contains everolimus, polyethylene glycol and hydroxypropyl cellulose, and is prepared by the following steps: heating for melting everolimus and polyethylene glycol; adding the molten liquid into an alcohol solution of hydroxypropyl cellulose, and uniformly stirring; and finally, granulating the suspension on pharmaceutically acceptable auxiliaries, drying and tabletting. Compared with the prior art, the everolimus tablet has the advantage of quick dissolution.
Description
Technical field
The invention belongs to pharmaceutical technology field, be specifically related to a kind of everolimus tablet.
Background technology
Everolimus (everolimus), molecular formula: C53H83NO14, molecular weight: 958.22, structural formula is as follows:
Everolimus is the inhibitor (rapamycin mammal target spot) of a kind of mTOR, PI3K/AKT passage downstream
A kind of serine threonine kinases.Everolimus is developed at first by Novartis Co., Ltd of Switzerland (NovartiS), trade name
Certican, lists in Sweden, captured European market in 2006 the most comprehensively for 2003 first.
FDA ratifies it and treats, for Sutent or Sorafenib, the patient that advanced renal cell cancer is failed, according to the research of Novartis, depends on
Wei Mosi can slow down the growth of kidney cancer cell, reduces the mortality rate of 67%.By growth and the propagation of suppression tumor cell,
Directly act on tumor cell；Occurred by suppression blood vessel, cause tumor vessel distribution to reduce and play indirect action and (pass through
The propagation generating the endotheliocyte induced with VEGF of effectively suppression tumor cell VEGF).
2010, everolimus was approved for preventing heart and the organ rejection of renal transplant recipients.Additionally, except nephrocyte
Rejection after cancer and organ transplantation, everolimus the most carrying out to neuroendocrine tumor, lymphoma, other cancers and
The research of tuberous sclerosis, can share as unitary agent or with existing cancer treatment method.
Everolimus is white to micro-yellow powder, lipotropy, and when 25 DEG C, in water, dissolubility, less than 0.01% (g/ml), therefore carries
Its dissolution high is particularly important.
Chinese invention patent CN102138903A discloses a kind of Everolimus solid oral medicinal composition, including Yi Weimo
Department's or derivatives thereof and the compositions of excipient composition, the pH value of the aqueous solution of described compositions is 4～7, described Yi Weimo
It is 0.05～5% that department's or derivatives thereof accounts for the percentage by weight of described compositions, is carried out principal agent all by fluid bed technique for packing
Even dispersion.Its shortcoming is complicated process of preparation, and production operation difficulty is big, and cost is high；Preparation process is used water or other
Solvent and need heating, the impurity of the drug causing preparation is big, poor stability.
Chinese invention patent CN 103610646 A discloses the preparation method of a kind of solid dispersion containing everolimus, the party
Method be everolimus is dissolved in organic solvent with a kind of polymer support HPMC after, be spray-dried by centrifugation and prepare.Its shortcoming
It is that the use of organic solvent can or can not produce impact and the residue problem of organic solvent, equipment to everolimus and excipient
Problem, human users's safety problem, the test problems etc. of residual solvent, not only can increase the complexity of operating procedure, also deposit
In potential safety hazard, add cost simultaneously.
At present, Novartis has listed tablet and the dispersible tablet of everolimus, but wherein contains ditertbutylparacresol.Two tertiary fourths
Base paracresol is a kind of oil-soluble organic compound, because it can produce oxygen in chemical reaction, and the food that slows down with free radical
Change the speed of reduction reaction, thus can keep the color of food, aroma and flavor, mainly be used as in food additive
Antioxidant.Owing to ditertbutylparacresol has a hypotoxicity, and make moist or illumination all can cause rotten, Japan, Rome Buddhist nun
The ground such as Asia, Sweden, Australia, the U.S. are all forbidden adding in food.The listing preparation of Novartis with the addition of the tertiary fourth of antioxidant two
Base paracresol, affects the character of product, brings safety risks to patient medication.
Summary of the invention
For the deficiencies in the prior art, inventor intends providing a kind of energy dissolution rapid everolimus tablet.
Specifically, the present invention is realized by following technology:
Everolimus tablet of the present invention, containing everolimus, Polyethylene Glycol, hydroxypropyl cellulose, by the following method
It is prepared from: everolimus, Polyethylene Glycol add heat fusing, this fused solution is joined in the ethanol solution of hydroxy propyl cellulose,
Stirring, finally will pelletize on the most acceptable for this suspension adjuvant, be dried, tabletting forms.
Described everolimus tablet, everolimus is 1:0.5-1.5 with the weight ratio of Polyethylene Glycol；Preferably, weight ratio
For 1:1.
Described everolimus tablet, everolimus is 1:3-5 with the weight ratio of hydroxypropyl cellulose；Preferably, weight ratio
For 1:4.
Described everolimus tablet, described pharmaceutically acceptable adjuvant is mannitol, carboxymethyl starch sodium, magnesium stearate.
Described everolimus tablet, described pharmaceutically acceptable adjuvant is microcrystalline Cellulose, carboxymethyl starch sodium, tristearin
Acid magnesium.
Compared with prior art, drug-eluting of the present invention is rapid.
Detailed description of the invention
Following example further describe beneficial effects of the present invention, and embodiment is only used for the purpose of illustration, is not intended to the present invention
Scope, those of ordinary skill in the art obvious are changed and modification is also contained in this according to what the present invention made simultaneously
Within the scope of bright.
Embodiment 1
Preparation technology:
Everolimus, Macrogol 4000 add heat fusing at 80 DEG C, and the hydroxypropyl that this fused solution joins recipe quantity is fine
In the ethanol solution of dimension element, stir, finally will pelletize on the most acceptable for this suspension adjuvant, be dried, pressure
Sheet forms.
Embodiment 2
Preparation technology:
Everolimus, Macrogol 4000 add heat fusing at 70 DEG C, and the hydroxypropyl that this fused solution joins recipe quantity is fine
In the ethanol solution of dimension element, stir, finally will pelletize on the most acceptable for this suspension adjuvant, be dried, pressure
Sheet forms.
Embodiment 3
Preparation technology:
Everolimus, Macrogol 4000 add heat fusing at 70 DEG C, and the hydroxypropyl that this fused solution joins recipe quantity is fine
In the ethanol solution of dimension element, stir, finally will pelletize on the most acceptable for this suspension adjuvant, be dried, pressure
Sheet forms.
Comparative example 1
Preparation technology:
Recipe quantity weighed the everolimus of 200 mesh sieves, Macrogol 4000 joins the second of hydroxypropyl cellulose of recipe quantity
In alcoholic solution, stirring, finally pelletized on the most acceptable adjuvant by this suspension, be dried, tabletting forms.
Checking embodiment
Dissolution determination.Take this product, according to dissolution method (Chinese Pharmacopoeia two annex XC the 3rd methods of version in 2010),
With 0.1% lauryl sodium sulfate aqueous solution 500ml as dissolution medium, rotating speed is 50 turns per minute, operates in accordance with the law, through 3,
5,15 minutes time, take solution appropriate, filter, take subsequent filtrate as need testing solution.Another precision weighs everolimus comparison
Product about 12.5mg, is placed in 50ml measuring bottle, first adds second eyeball 5ml and makes it dissolve, then adds dissolution medium to scale, shakes
Even, precision measures lml and is placed in 50ml measuring bottle, adds dissolution medium to scale, shakes up, as reference substance solution.Press
Chromatographic condition under assay item, precision measures each 100 microlitres of above two solution, injects chromatograph of liquid, records color
Spectrogram, is calculated the stripping quantity of every by external standard method with main peak and isomer peak area sum.
Table 1 each embodiment measurement result
| Embodiment | 3min dissolution (%) | 5min dissolution (%) | 15min dissolution (%) |
| Embodiment 1 | 99.8 | 99.9 | 99.9 |
| Embodiment 2 | 99.8 | 99.9 | 100.1 |
| Embodiment 3 | 100.1 | 100.1 | 100.1 |
| Comparative example 1 | 43.5 | 60.4 | 77.2 |
As seen from the table, embodiment of the present invention dissolution is rapid；Comparative example 1, adds Polyethylene Glycol, but does not melts system
Grain, dissolution is slow compared with the present invention.
Claims (7)
1. an everolimus tablet, it is characterised in that containing everolimus, Polyethylene Glycol, hydroxypropyl cellulose, by such as
Lower section method is prepared from: everolimus, Polyethylene Glycol add heat fusing, by molten for the ethanol that this fused solution joins hydroxy propyl cellulose
In liquid, stirring, finally will pelletize on the most acceptable for this suspension adjuvant, be dried, tabletting forms.
Everolimus tablet the most according to claim 1, it is characterised in that everolimus and the weight ratio of Polyethylene Glycol
For 1:0.5-1.5.
Everolimus tablet the most according to claim 1, it is characterised in that everolimus and the weight ratio of Polyethylene Glycol
For 1:1.
Everolimus tablet the most according to claim 1, it is characterised in that everolimus and the weight of hydroxypropyl cellulose
Amount ratio is 1:3-5.
Everolimus tablet the most according to claim 1, it is characterised in that everolimus and the weight of hydroxypropyl cellulose
Amount ratio is 1:4.
Everolimus tablet the most according to claim 1, it is characterised in that described pharmaceutically acceptable adjuvant is sweet
Dew alcohol, carboxymethyl starch sodium, magnesium stearate.
Everolimus tablet the most according to claim 1, it is characterised in that described pharmaceutically acceptable adjuvant is micro-
Crystalline cellulose, carboxymethyl starch sodium, magnesium stearate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510404952.4A CN106309387B (en) | 2015-07-11 | 2015-07-11 | Everolimus tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510404952.4A CN106309387B (en) | 2015-07-11 | 2015-07-11 | Everolimus tablet |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106309387A true CN106309387A (en) | 2017-01-11 |
| CN106309387B CN106309387B (en) | 2020-04-24 |
Family
ID=57725678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510404952.4A Active CN106309387B (en) | 2015-07-11 | 2015-07-11 | Everolimus tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106309387B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111643461A (en) * | 2019-03-04 | 2020-09-11 | 鲁南制药集团股份有限公司 | Tablet for treating hypertension and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1488346A (en) * | 2002-10-09 | 2004-04-14 | 重庆太极医药研究院 | Melatonin two-layer release-controlled tablet and preparing process thereof |
| CN102525876A (en) * | 2010-12-15 | 2012-07-04 | 西安力邦医药科技有限责任公司 | Aspirin solid dispersion, as well as preparation method, pharmaceutical composition and use thereof |
| CN103099790A (en) * | 2011-11-11 | 2013-05-15 | 山东新时代药业有限公司 | Tablet containing everolimus and preparation method thereof |
| CN103585122A (en) * | 2012-08-17 | 2014-02-19 | 山东新时代药业有限公司 | Tablet containing everolimus, and preparation method thereof |
-
2015
- 2015-07-11 CN CN201510404952.4A patent/CN106309387B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1488346A (en) * | 2002-10-09 | 2004-04-14 | 重庆太极医药研究院 | Melatonin two-layer release-controlled tablet and preparing process thereof |
| CN102525876A (en) * | 2010-12-15 | 2012-07-04 | 西安力邦医药科技有限责任公司 | Aspirin solid dispersion, as well as preparation method, pharmaceutical composition and use thereof |
| CN103099790A (en) * | 2011-11-11 | 2013-05-15 | 山东新时代药业有限公司 | Tablet containing everolimus and preparation method thereof |
| CN103585122A (en) * | 2012-08-17 | 2014-02-19 | 山东新时代药业有限公司 | Tablet containing everolimus, and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111643461A (en) * | 2019-03-04 | 2020-09-11 | 鲁南制药集团股份有限公司 | Tablet for treating hypertension and preparation method thereof |
| CN111643461B (en) * | 2019-03-04 | 2022-09-13 | 鲁南制药集团股份有限公司 | Tablet for treating hypertension and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106309387B (en) | 2020-04-24 |
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