CN101862305A - Ambroxol hydrochloride sustained-release pellet and preparation method - Google Patents

Ambroxol hydrochloride sustained-release pellet and preparation method Download PDF

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CN101862305A
CN101862305A CN200910082237A CN200910082237A CN101862305A CN 101862305 A CN101862305 A CN 101862305A CN 200910082237 A CN200910082237 A CN 200910082237A CN 200910082237 A CN200910082237 A CN 200910082237A CN 101862305 A CN101862305 A CN 101862305A
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release
slow
release micro
pill
preparation
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CN101862305B (en
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孟凡静
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AVENTIS PHARMA (HAINAN) Co.,Ltd.
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Beijing Dezhong Wanquan Medicines Technological Development Co Ltd
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Abstract

The invention relates to the composition of an ambroxol HCl-containing sustained-release pellet and a preparation method. The sustained-release pellet consists of two parts which are a quick-release pellet core and a sustained-release coating film respectively, can achieve the effect of long-term release approaching to zero-order release, is mainly used for treating acute and chronic respiratory diseases, and is a medicament of first choice for dispelling phlegm.

Description

A kind of ambroxol hydrochloride sustained-release pellet and preparation method
Technical field
The present invention relates to a kind of composition and preparation method that contains the slow-release micro-pill of ambroxol hydrochloride, this slow-release micro-pill is made up of the rapid release ball heart and slow release coatings two parts, can reach the long-term releasing effect that discharges near zero level, being mainly used in the treatment of acute and chronic respiratory tract disease, is the choice drug that eliminates the phlegm.
Background technology
Ambroxol hydrochloride Ambroxol HCl proves in clinical trial: this product scalable serosity and mucous secretion, promote the synthetic of lung surface active material, and strengthen fibre swing, increase the removing ability of mucociliary transportation system.These product also can increase the respiratory tract liquid measure, reduce mucous secretion, can promote the secretion and the bronchus ciliary movement of pulmonary surfactant, make expectorant be easy to expectoration.Be applicable to acute, chronic respiratory tract disease that companion's sputum is secreted undesired and expectoration dysfunction clinically.The for example treatment of the prophylactic treatment of chronic bronchitis acute exacerbation, asthmatic bronchitis, bronchiectasis and san bronchial asthma, postoperative pulmonary complication and premature infant and new-born baby respiratory distress syndrome.Ambroxol hydrochloride oral absorbs rapidly, eliminates half-life 2~3hr, and best dosage regimen is every day 1~2 time, is to improve compliance of patients, farthest reduces individual patient difference simultaneously, and the ambroxol hydrochloride controlled release preparation is studied.The sustained-release preparation that allows to be administered once every day is different from ordinary preparation by the release that prolongs active substance.
Patent CN100370977C has protected a kind of slow releasing tablet of ambroxol-hydrochloride-containing active component, though can reach the effect of slow release, can't reach releasing effect near zero level, and because the interior environment of human stomach, slow releasing tablet is difficult to reach uniform release, and the diversity of release is bigger; Patent CN1546008A has protected a kind of ambroxol hydrochloride liquid slow releasing preparation and preparation method thereof, though can reach uniform release at gastric, packing cost is higher, and transportation inconvenience; Patent CN1415287A discloses a kind of ambroxol hydrochloride osmotic pump type controlled release preparation and preparation method thereof, though can reach even release at gastric, and convenient transportation, in preparation process, need special equipment, production cost height, difficult experiment industrialization.
The invention provides a kind of ambroxol hydrochloride sustained-release pellet that can reach,, can be dispersed into micropill at gastric with capsular form administration near the zero level releasing effect, can reach comparatively uniformly and discharge, and production cost is comparatively moderate, industrialization level height, convenient transportation.
Summary of the invention
The invention provides a kind of slow-release micro-pill that contains ambroxol hydrochloride, this slow-release micro-pill is made up of the rapid release ball heart and coatings, and coatings wherein comprises contagion gown layer and sustained-release coating layer again.
This slow-release micro-pill provided by the invention, the rapid release ball heart is made up of 25~40% ambroxol hydrochloride and pharmaceutic adjuvant.
This slow-release micro-pill provided by the invention, pharmaceutic adjuvant comprises filler, disintegrating agent and binding agent.
This slow-release micro-pill provided by the invention, filler are lactose, starch, microcrystalline Cellulose, mannitol, and its shared percentage by weight is 60~70%.
This slow-release micro-pill provided by the invention, disintegrating agent are cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, polyvinylpolypyrrolidone or low-substituted hydroxypropyl methylcellulose, and its shared weight percent is 2~8%.
This slow-release micro-pill provided by the invention, the percentage by weight of contagion gown layer in slow-release micro-pill is 2~6%, the hypromellose by 5~8%, 0.5% Polyethylene Glycol and Pulvis Talci are formed.
This slow-release micro-pill provided by the invention, the percentage by weight of sustained-release coating layer in slow-release micro-pill is 8~20%, the You Teqi by 8~15%, 0.5% plasticizer and Pulvis Talci are formed.
This slow-release micro-pill provided by the invention, its preparation method is:
1) preparation of the rapid release ball heart: with the raw material of recipe quantity and filler, disintegrating agent mixing,, be prepared into the micropill that diameter is 1mm~2mm, dry in the baking oven, sieve out the ball heart that is of moderate size with extruding spheronizator with suitable amount of adhesive system soft material;
2) bag contagion gown: hypromellose, Polyethylene Glycol and the Pulvis Talci of recipe quantity are placed 50% pure water, stir, it is fully dissolved or disperses, coating increases weight to 2~6%;
3) bag extended release coatings: You Teqi, plasticizer and the Pulvis Talci of recipe quantity are placed 95% ethanol, stir, it is fully dissolved or disperses, coating increases weight to 8~20%;
4) with the micropill fill capsule behind the coating.
This slow-release micro-pill provided by the invention is mainly used in the treatment of acute and chronic respiratory tract disease, is the choice drug that eliminates the phlegm
The specific embodiment
Specifying the present invention in conjunction with the embodiments, but be not limited to following embodiment.Wherein " % " is meant " weight % ".
Embodiment 1
The preparation of the ball heart
Figure B2009100822378D0000031
Preparation technology:
Ambroxol hydrochloride and lactose, crosslinked carboxymethyl fecula sodium, microcrystalline Cellulose mixing, the polyvidone aqueous solution with 10% is a binding agent system soft material, prepares micropill with extruding spheronizator, the micropill about diameter 1mm is sieved out in the oven dry of spending the night, as the ball heart.
The contagion gown layer
Figure B2009100822378D0000032
Hypromellose, Polyethylene Glycol and the Pulvis Talci of recipe quantity are placed 50% pure water, stir, it is fully dissolved or disperses, coating increases weight to 2%.
Sustained-release coating layer
Figure B2009100822378D0000041
You Teqi, triethyl citrate and the Pulvis Talci of recipe quantity are placed 95% ethanol, stir, it is fully dissolved or disperses, coating increases weight to 8%;
With the micropill fill capsule behind the coating, promptly.
Embodiment 2
The preparation of the ball heart
Figure B2009100822378D0000042
Preparation technology:
Ambroxol hydrochloride and mannitol, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose mixing, the hypromellose aqueous solution with 8% is a binding agent system soft material, prepares micropill with extruding spheronizator, the micropill about diameter 1mm is sieved out in the oven dry of spending the night, as the ball heart.
The contagion gown layer
Figure B2009100822378D0000043
Figure B2009100822378D0000051
Hypromellose, Polyethylene Glycol and the Pulvis Talci of recipe quantity are placed 50% pure water, stir, it is fully dissolved or disperses, coating increases weight to 4%.
Sustained-release coating layer
Figure B2009100822378D0000052
You Teqi, dibutyl phthalate and the Pulvis Talci of recipe quantity are placed 95% ethanol, stir, it is fully dissolved or disperses, coating increases weight to 15%;
With the micropill fill capsule behind the coating, promptly.
Embodiment 3
The preparation of the ball heart
Figure B2009100822378D0000053
Preparation technology:
Ambroxol hydrochloride and starch, polyvinylpolypyrrolidone, microcrystalline Cellulose mixing, the starch slurry with 10% are binding agent system soft material, prepare micropill with extruding spheronizator, and the micropill about diameter 1mm is sieved out in the oven dry of spending the night, as the ball heart;
The contagion gown layer
Figure B2009100822378D0000061
Hypromellose, Polyethylene Glycol and the Pulvis Talci of recipe quantity are placed 50% pure water, stir, it is fully dissolved or disperses, coating increases weight to 6%.
Sustained-release coating layer
You Teqi, dioctyl phthalate and the Pulvis Talci of recipe quantity are placed 95% ethanol, stir, it is fully dissolved or disperses, coating increases weight to 15%;
With the micropill fill capsule behind the coating, promptly.
Embodiment 4
Get the sample of embodiment 1 preparation, detect its release in vitro degree according to 2005 editions officinal methods, its release profiles as shown in Figure 1.
As can be seen from Figure, this product release in 4 hours reaches maximum, and the release in vitro before 4 hours can reach zero level substantially and discharge, and meets officinal regulation.

Claims (9)

1. a slow-release micro-pill that contains ambroxol hydrochloride is characterized in that being made up of the rapid release ball heart and coatings.
2. slow-release micro-pill according to claim 1 is characterized in that the described rapid release ball heart is made up of 25~40% ambroxol hydrochloride and pharmaceutic adjuvant.
3. slow-release micro-pill according to claim 2 is characterized in that described pharmaceutic adjuvant comprises filler, disintegrating agent and binding agent.
4. slow-release micro-pill according to claim 3 is characterized in that described filler is lactose, starch, microcrystalline Cellulose, mannitol, and its shared percentage by weight is 60~70%.
5. slow-release micro-pill according to claim 3 is characterized in that described disintegrating agent is cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, polyvinylpolypyrrolidone or low-substituted hydroxypropyl methylcellulose, and its shared weight percent is 2~8%.
6. slow-release micro-pill according to claim 1 is characterized in that described coatings is made up of contagion gown layer and sustained-release coating layer.
7. slow-release micro-pill according to claim 6 is characterized in that the percentage by weight of described contagion gown layer in slow-release micro-pill is 2~6%, and the hypromellose by 5~8%, 0.5% Polyethylene Glycol and Pulvis Talci are formed.
8. slow-release micro-pill according to claim 6 is characterized in that the percentage by weight of described sustained-release coating layer in slow-release micro-pill is 8~20%, and the You Teqi by 8~15%, 0.5% plasticizer and Pulvis Talci are formed.
9. slow-release micro-pill according to claim 1, its preparation method is:
1) preparation of the rapid release ball heart: with the raw material of recipe quantity and filler, disintegrating agent mixing,, be prepared into the micropill that diameter is 1mm~2mm, dry in the baking oven, sieve out the ball heart that is of moderate size with extruding spheronizator with suitable amount of adhesive system soft material;
2) bag contagion gown: hypromellose, Polyethylene Glycol and the Pulvis Talci of recipe quantity are placed 50% pure water, stir, it is fully dissolved or disperses, coating increases weight to 2~6%;
3) bag extended release coatings: You Teqi, plasticizer and the Pulvis Talci of recipe quantity are placed 95% ethanol, stir, it is fully dissolved or disperses, coating increases weight to 8~20%;
4) with the micropill fill capsule behind the coating.
CN200910082237.8A 2009-04-20 2009-04-20 Ambroxol hydrochloride sustained-release pellet and preparation method Active CN101862305B (en)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102266293A (en) * 2011-07-21 2011-12-07 佛山市隆信医药科技有限公司 Ambroxol hydrochloride sustained-release dry suspension and preparation method thereof
CN102772391A (en) * 2012-08-16 2012-11-14 河南新帅克制药股份有限公司 Ambroxol hydrochloride sustained release capsule and preparation method thereof
CN103054832A (en) * 2012-12-26 2013-04-24 河南中帅医药科技发展有限公司 Minocycline hydrochloride sustained-release capsule and preparation method thereof
CN103211789A (en) * 2012-01-18 2013-07-24 北京天衡药物研究院 Ambroxol hydrochloride film-controlled slow-release pellet capsule
CN105456202A (en) * 2015-12-08 2016-04-06 青岛正大海尔制药有限公司 Ambroxol and salbutamol pellet
CN107569473A (en) * 2017-09-28 2018-01-12 南京易亨制药有限公司 A kind of Sustained Release Ambroxol Hydrochloride Capsules and preparation method thereof

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KR930011993B1 (en) * 1991-12-23 1993-12-23 주식회사 럭키 Process for preparing prolonged release of ambroxol preparation
US6251429B1 (en) * 1991-12-11 2001-06-26 Therapicon Slr Programmed release ambroxol—HCl dosage forms
CN1415287A (en) * 2002-11-28 2003-05-07 沈阳药科大学 Hydrochloric ambroxol osmotic pump type controlled release formulation and its preparation method
CN1600296A (en) * 2003-09-22 2005-03-30 北京德众万全药物技术开发有限公司 Method for preparing tiny pellets of difficult soluble drugs and formulation containing the pellets
JP2008013480A (en) * 2006-07-05 2008-01-24 Sawai Pharmaceutical Co Ltd Drug-containing micro-particle and method for producing the same
CN101288659A (en) * 2007-04-18 2008-10-22 王雷波 Floating type pellets in stomach and preparation method thereof

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* Cited by examiner, † Cited by third party
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US6251429B1 (en) * 1991-12-11 2001-06-26 Therapicon Slr Programmed release ambroxol—HCl dosage forms
KR930011993B1 (en) * 1991-12-23 1993-12-23 주식회사 럭키 Process for preparing prolonged release of ambroxol preparation
CN1415287A (en) * 2002-11-28 2003-05-07 沈阳药科大学 Hydrochloric ambroxol osmotic pump type controlled release formulation and its preparation method
CN1600296A (en) * 2003-09-22 2005-03-30 北京德众万全药物技术开发有限公司 Method for preparing tiny pellets of difficult soluble drugs and formulation containing the pellets
JP2008013480A (en) * 2006-07-05 2008-01-24 Sawai Pharmaceutical Co Ltd Drug-containing micro-particle and method for producing the same
CN101288659A (en) * 2007-04-18 2008-10-22 王雷波 Floating type pellets in stomach and preparation method thereof

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佟杰: "复方罗红霉素缓释微丸胶囊的研制", 《中国优秀硕士学位论文全文数据库》 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102266293A (en) * 2011-07-21 2011-12-07 佛山市隆信医药科技有限公司 Ambroxol hydrochloride sustained-release dry suspension and preparation method thereof
CN102266293B (en) * 2011-07-21 2013-05-01 佛山市隆信医药科技有限公司 Ambroxol hydrochloride sustained-release dry suspension and preparation method thereof
CN103211789A (en) * 2012-01-18 2013-07-24 北京天衡药物研究院 Ambroxol hydrochloride film-controlled slow-release pellet capsule
CN103211789B (en) * 2012-01-18 2017-07-11 北京天衡药物研究院有限公司 Ambroxol hydrochloride film-controlled slow-release micro pill capsule
CN102772391A (en) * 2012-08-16 2012-11-14 河南新帅克制药股份有限公司 Ambroxol hydrochloride sustained release capsule and preparation method thereof
CN103054832A (en) * 2012-12-26 2013-04-24 河南中帅医药科技发展有限公司 Minocycline hydrochloride sustained-release capsule and preparation method thereof
CN105456202A (en) * 2015-12-08 2016-04-06 青岛正大海尔制药有限公司 Ambroxol and salbutamol pellet
CN107569473A (en) * 2017-09-28 2018-01-12 南京易亨制药有限公司 A kind of Sustained Release Ambroxol Hydrochloride Capsules and preparation method thereof

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Denomination of invention: A sustained-release microsphere of ambroxol hydrochloride and its preparation method

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