CN101961324A - Prescription and preparation method of etofbrate release capsules - Google Patents
Prescription and preparation method of etofbrate release capsules Download PDFInfo
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- CN101961324A CN101961324A CN 201010277529 CN201010277529A CN101961324A CN 101961324 A CN101961324 A CN 101961324A CN 201010277529 CN201010277529 CN 201010277529 CN 201010277529 A CN201010277529 A CN 201010277529A CN 101961324 A CN101961324 A CN 101961324A
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- etofibrate
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- XXRVYAFBUDSLJX-UHFFFAOYSA-N CC(C)(C(OCCOC(c1cccnc1)=O)=O)Oc(cc1)ccc1Cl Chemical compound CC(C)(C(OCCOC(c1cccnc1)=O)=O)Oc(cc1)ccc1Cl XXRVYAFBUDSLJX-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention provides a prescription and a preparation method of etofbrate release capsules. The prescription comprises a main medicament and an enteric material. Pattern drawing is performed by adopting enteric ethanol or ethanol-acetone solution of methacrylic acid copolymer, polyacrylic resin or phthalic acid ethyl cellulose so as to capsule the etofbrate into small pills with release characteristic; and then the small coated pills are filled in enteric empty capsules.
Description
Technical field the invention belongs to field of pharmaceutical preparations, relates to a kind of prescription and preparation method of etofibrate slow releasing capsule.
Background technology etofibrate (Etofbrate), phenoxy acetic acid class and nicotinic acid class blood lipid regulation medicine by the research and development of German Merz company are the complex of clofibrate and nicotinic acid, are a kind of blood lipid regulation new drugs of broad-spectrum high efficacy rate.Be decomposed into clofibrate and nicotinic acid generation effect rapidly behind the clothes in vivo, and effect is lasting, be characterized in to suppress the synthetic of cholesterol and triglyceride, increase the drainage of steroid, the clinical reduction plasma triglyceride that is mainly used in, be applicable to hyperlipidemia (serious constitutional and Secondary cases hyperlipidemia), arterial pulse is atherosis, cerebrovascular and terminal angiopathy, blood vessel and retinal vasculopathy, prevention of stroke, heart change, cardiac muscle be plug, hypertension, hyperlipidemia obesity, disturbance of blood circulation etc. more.Etofibrate both can reduce triglyceride concentration in the blood, can improve high density ester gp concentration again, reduced low-density ester gp concentration.
The etofibrate chemical structural formula:
Molecular formula C
18H
18ClNO
5, molecular weight 363.79, etofibrate is insoluble in water.
US5957764 discloses a kind of method for preparing the etofibrate hard capsule, being about to etofibrate adds acetone and makes the wet particle of 14-20 purpose, after removing acetone, rescreen the dried particle of telling 300-1000 μ m, again at the mixed material of its outsourcing with a certain proportion of etofibrate and Polyethylene Glycol, adhesive adopts the cold acetone saturated solution of etofibrate, reaches the piller of 400-2000 μ m, the 500mg etofibrate of can packing into to particle diameter in the 0# capsule.And EP0625351B1 discloses a kind of method that adopts the Lac coating to prepare etofibrate slowbreak preparation, earlier with etofibrate with after sucrose, starch mix, the alcoholic solution that adds Lac is made the dried particle of 125-800 μ m, and then in its outsourcing with etofibrate, adhesive adopts ethanol, obtain the piller of 630-1250 μ m, again at the Lac of its outsourcing, in the 0# capsule of packing at last with enteric.This preparation method can obtain etofibrate content and reach piller more than 96%, thereby in the 0# capsule of it can being packed into.
The method of United States Patent (USP) is granulated because of adopting acetone, have greater environmental impacts, and the capsular slow release effect that makes is relatively poor; Though the method for European patent can be packed 500mg in the 0# capsule, adopt Lac to have coating membrane release shakiness as enteric-coating material, be placed with for a long time may cause in the intestinal juice insoluble, and the difficult control of technology in the coating process.
Summary of the invention purpose of the present invention provides the prescription and the method for the different preparation etofibrate slow releasing capsule of a kind of and above-mentioned two kinds of methods just in order to overcome above-mentioned weak point of the prior art.
At first with starch and sucrose mixing, adopt methacrylic acid copolymer, polyacrylic resin or the cellulosic ethanol of phthalic acid second or the ethanol-acetone soln molding of enteric, the corning warp is the ball heart of 300-600 μ m, again in its outsourcing with etofibrate, adhesive is an ethanol, bread is with methacrylic acid copolymer, polyacrylic resin or the cellulosic enteric film coat of phthalic acid second outside more at last, and the content of etofibrate can be at 80-98% in the final piller.Every etofibrate sustained-release micro-pill capsules contains etofibrate 200-600mg, and preferred every contains etofibrate 500mg.
The etofibrate slow releasing capsule coating membrane release of the present invention's preparation is stable, and technology is easy to control.Blood drug level is steady, and is safer limited, the bioavailability height, and it is few that product is taken number of times, takes more convenient.
Specific embodiment following examples only are further detailed the present invention, should not be construed as the present invention is further limited.
Embodiment 1The preparation of etofibrate slow releasing capsule
Step (1) is got sucrose 3.15kg and starch 1.05kg mixing, places centrifugal granulator, adds 5% phthalic acid second cellulose solution molding, sieves out grain through being that the particle of 300-600 μ m is as the ball heart.
Step (2) places centrifugal granulator with the 5.5kg ball heart, is wetting agent with ethanol, is dry powder with the etofibrate to ball medicine carrying in the heart, reaches 630-1250 μ m to particle diameter, adopts 5% phthalic acid second cellulose solution coating to satisfying the enteric requirement again.The content of etofibrate is at 80-98% in the piller.
Step (3) dress capsule is packed above-mentioned granule in the 2#-00# capsule into.
Embodiment 2The preparation of etofibrate slow releasing capsule
Step (1) is got sucrose 3.15kg and starch 1.05kg mixing, places centrifugal granulator, and the ethanol molding is sieved out grain through being that the particle of 300-600 μ m is as the ball heart.
Step (2) places centrifugal granulator with the 5.5kg ball heart, is wetting agent with ethanol, is dry powder with the etofibrate to ball medicine carrying in the heart, reaches 630-1250 μ m to particle diameter, adopts 5% phthalic acid second cellulose solution coating to satisfying the enteric requirement again.The content of etofibrate is at 80-98% in the piller.
Step (3) dress capsule is packed above-mentioned granule in the 2#-00# capsule into.
Embodiment 3The preparation of etofibrate slow releasing capsule
Step (1) is got sucrose 3.15kg and starch 1.05kg mixing, places centrifugal granulator, adds 5% polyacrylic resin alcoholic solution molding, sieves out grain through being that the particle of 300-600 μ m is as the ball heart.
Step (2) places centrifugal granulator with the 5.5kg ball heart, is wetting agent with ethanol, is dry powder with the etofibrate to ball medicine carrying in the heart, reaches 630-1250 μ m to particle diameter, adopts to add 5% polyacrylic resin alcoholic solution coating to satisfying the enteric requirement again.The content of etofibrate is at 80-98% in the piller.
Step (3) dress capsule is packed above-mentioned granule in the 2#-00# capsule into.
Embodiment 4The preparation of etofibrate slow releasing capsule
Step (1) is got sucrose 3.15kg and starch 1.05kg mixing, places centrifugal granulator, adds 5% methylmethacrylate copolymer alcoholic solution molding, sieves out grain through being that the particle of 300-600 μ m is as the ball heart.
Step (2) places centrifugal granulator with the 5.5kg ball heart, is wetting agent with ethanol, is dry powder with the etofibrate to ball medicine carrying in the heart, reaches 630-1250 μ m to particle diameter, adopts 5% methylmethacrylate copolymer alcoholic solution coating to satisfying the enteric requirement again.The content of etofibrate is at 80-98% in the piller.
Step (3) dress capsule is packed above-mentioned granule in the 2#-00# capsule into.
Embodiment 5The preparation of etofibrate slow releasing capsule
Step (1) is got sucrose 3.15kg and starch 1.05kg mixing, places centrifugal granulator, adds the molding of 5%L30D aqueous dispersion, sieves out grain through being that the particle of 300-600 μ m is as the ball heart.
Step (2) places centrifugal granulator with the 5.5kg ball heart, is wetting agent with ethanol, is dry powder with the etofibrate to ball medicine carrying in the heart, reaches 630-1250 μ m to particle diameter, adopts 5%L30D aqueous dispersion coating to satisfying the enteric requirement again.The content of etofibrate is at 80-98% in the piller.
Step (3) dress capsule is packed above-mentioned granule in the 2#-00# capsule into.
Embodiment 6The preparation of etofibrate slow releasing capsule
Step (1) is got sucrose 3.15kg and starch 1.05kg mixing, places centrifugal granulator, adds the molding of 5%E50D aqueous dispersion, sieves out grain through being that the particle of 300-600 μ m is as the ball heart.
Step (2) places centrifugal granulator with the 5.5kg ball heart, is wetting agent with ethanol, is dry powder with the etofibrate to ball medicine carrying in the heart, reaches 630-1250 μ m to particle diameter, adopts 5%E50D aqueous dispersion coating to satisfying the enteric requirement again.The content of etofibrate is at 80-98% in the piller.
Step (3) dress capsule is packed above-mentioned granule in the 2#-00# capsule into.
Etofibrate slow releasing capsule of the present invention has been carried out the test of release in vitro degree, and the result is as follows:
Effect embodiment 1The release in vitro degree test of etofibrate slow releasing capsule
Get this product, according to drug release determination method (two appendix X of Chinese Pharmacopoeia version in 2005 D, first method), adopting the device of dissolution method second method, is dissolution medium with the hydrochloric acid solution 900ml of 0.1mol/L, and rotating speed is that per minute 75 changes, operation in accordance with the law, got solution 10ml respectively and filter in the time of 1,4,7 hour, and the instant hydrochloric acid solution 10ml that replenishes 0.1mol/L in process container, precision is measured filtrate 1ml and is put in the 10ml measuring bottle, add the stripping medium to scale, shake up.It is an amount of that precision takes by weighing the etofibrate reference substance in addition, makes the solution that contains 33 μ g among every 1ml approximately with dissolution medium.Get above-mentioned two kinds of solution respectively, according to ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2005 A), wavelength place at 262nm measures trap respectively, calculate every burst size at different time, every of this product should should be 20-40%, the 50-75% of labelled amount respectively mutually in 1,4 burst sizes during with 7 hours, more than 75%.Result of the test:
| Product | 1 hour burst size (%) | 4 hours burst sizes (%) | 7 hours burst sizes (%) |
| Embodiment 1 | 38.6 | 72.3 | 85.4 |
| Embodiment 2 | 30.4 | 68.6 | 87.9 |
| Embodiment 3 | 38.7 | 70.3 | 85.7 |
| Embodiment 4 | 35.2 | 72.4 | 88.6 |
| Embodiment 5 | 39.0 | 65.8 | 89.5 |
| Embodiment 6 | 33.6 | 69.7 | 90.2 |
The etofibrate slow releasing capsule that result of the test confirms to prepare in the embodiment of the invention in the hydrochloric acid solution of 0.1mol/L, in 1,4 burst sizes during with 7 hours should be 20-40%, the 50-75% of labelled amount respectively mutually, more than 75%.
Claims (6)
1. the prescription of an etofibrate sustained-release micro-pill capsules and preparation method.
2. the described prescription of claim 1 is made up of etofibrate and adjuvant thereof.
3. the described adjuvant of claim 2 is methacrylic acid copolymer, polyacrylic resin or phthalic acid second cellulose.
4. the described preparation method of claim 1 is: at first with starch and sucrose mixing, adopt methacrylic acid copolymer, polyacrylic resin or the cellulosic ethanol of phthalic acid second or the ethanol-acetone soln molding of enteric, the corning warp is the ball heart of 300-600 μ m, again in its outsourcing with etofibrate, adhesive is an ethanol, at last more outside bread with methacrylic acid copolymer, polyacrylic resin or the cellulosic enteric film coat of phthalic acid second.
In the described etofibrate slow-release micro-pill of claim 1 content of etofibrate at 80-98%.
6. every of the described etofibrate sustained-release micro-pill capsules of claim 1 contains etofibrate 200-600mg.
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| CN 201010277529 CN101961324A (en) | 2010-09-10 | 2010-09-10 | Prescription and preparation method of etofbrate release capsules |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579366A (en) * | 2012-03-23 | 2012-07-18 | 南京泽恒医药技术开发有限公司 | Method for preparing Etofibrate sustained-release pellet |
| CN103091420A (en) * | 2013-01-16 | 2013-05-08 | 山东鲁北药业有限公司 | Method for determining etofibrate related substance by using high performance liquid chromatography |
| CN105769767A (en) * | 2016-04-12 | 2016-07-20 | 武汉理工大学 | Etofibrate self-emulsifying preparation and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4957746A (en) * | 1984-06-29 | 1990-09-18 | Roberto Valducci | Process for preparing etofibrate or similar compounds containing sustained release microgranules and products thus obtained |
| CN1697649A (en) * | 2003-04-29 | 2005-11-16 | 罗姆两合公司 | Dosage form and method for producing the same |
| CN1726024A (en) * | 2002-12-17 | 2006-01-25 | 阿伯特有限及两合公司 | Formulation comprising fenofibric acid, a physiologically acceptable salt or derivative thereof |
| CN101120931A (en) * | 2006-08-07 | 2008-02-13 | 珠海天翼医药技术开发有限公司 | Bezafibrate sustained-release composition |
| CN101594850A (en) * | 2006-12-21 | 2009-12-02 | 兰贝克赛实验室有限公司 | Antilipidemic pharmaceutical compositions and and preparation method thereof |
| CN101626769A (en) * | 2007-02-22 | 2010-01-13 | 赢创罗姆有限责任公司 | Pellets comprising an active substance matrix and a polymer coating, and a method for producing said pellets |
-
2010
- 2010-09-10 CN CN 201010277529 patent/CN101961324A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4957746A (en) * | 1984-06-29 | 1990-09-18 | Roberto Valducci | Process for preparing etofibrate or similar compounds containing sustained release microgranules and products thus obtained |
| CN1726024A (en) * | 2002-12-17 | 2006-01-25 | 阿伯特有限及两合公司 | Formulation comprising fenofibric acid, a physiologically acceptable salt or derivative thereof |
| CN1697649A (en) * | 2003-04-29 | 2005-11-16 | 罗姆两合公司 | Dosage form and method for producing the same |
| CN101120931A (en) * | 2006-08-07 | 2008-02-13 | 珠海天翼医药技术开发有限公司 | Bezafibrate sustained-release composition |
| CN101594850A (en) * | 2006-12-21 | 2009-12-02 | 兰贝克赛实验室有限公司 | Antilipidemic pharmaceutical compositions and and preparation method thereof |
| CN101626769A (en) * | 2007-02-22 | 2010-01-13 | 赢创罗姆有限责任公司 | Pellets comprising an active substance matrix and a polymer coating, and a method for producing said pellets |
Non-Patent Citations (1)
| Title |
|---|
| 《广东药学》 19971231 黄湘兰等 依托贝特缓释胶囊释放度测定的研究 16-18 1-6 , 第2期 2 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579366A (en) * | 2012-03-23 | 2012-07-18 | 南京泽恒医药技术开发有限公司 | Method for preparing Etofibrate sustained-release pellet |
| CN103091420A (en) * | 2013-01-16 | 2013-05-08 | 山东鲁北药业有限公司 | Method for determining etofibrate related substance by using high performance liquid chromatography |
| CN105769767A (en) * | 2016-04-12 | 2016-07-20 | 武汉理工大学 | Etofibrate self-emulsifying preparation and preparation method thereof |
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Open date: 20110202 |