CN105748445A - 一种非诺贝酸胆碱缓释胶囊的制备方法 - Google Patents

一种非诺贝酸胆碱缓释胶囊的制备方法 Download PDF

Info

Publication number
CN105748445A
CN105748445A CN201610194181.5A CN201610194181A CN105748445A CN 105748445 A CN105748445 A CN 105748445A CN 201610194181 A CN201610194181 A CN 201610194181A CN 105748445 A CN105748445 A CN 105748445A
Authority
CN
China
Prior art keywords
film
preparation
medicine carrying
fenofibric acid
capsule core
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201610194181.5A
Other languages
English (en)
Inventor
熊富良
张雪琼
周利娟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
WUHAN YAOGU BIO-TECH Co Ltd
Original Assignee
WUHAN YAOGU BIO-TECH Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by WUHAN YAOGU BIO-TECH Co Ltd filed Critical WUHAN YAOGU BIO-TECH Co Ltd
Priority to CN201610194181.5A priority Critical patent/CN105748445A/zh
Publication of CN105748445A publication Critical patent/CN105748445A/zh
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose

Abstract

本发明公开了一种非诺贝酸胆碱缓释胶囊的制备方法，它包括载药丸芯的制备、包薄膜衣、包肠溶衣等工艺步骤。本发明制备的非诺贝酸胆碱的缓释胶囊与同类产品相比，释放速度更快，而且释放更加完全。

Description

一种非诺贝酸胆碱缓释胶囊的制备方法
技术领域
本发明属于药物制剂领域，具体涉及一种非诺贝酸胆碱缓释胶囊的制备方法。
背景技术
非诺贝酸胆碱的化学名为2-[4-(氯苯甲酰)苯氧基]-2-甲基丙酸胆碱盐，结构式如下：
美国FDA批准其可单独用于重度高甘油三酯血症患者，降低TG。也可单独用于原发性高血脂症和混合血脂异常患者，以降低患者升高的LDL-C、总胆固醇、TG和载脂蛋白B水平，并提升患者的HDL-C水平。
目前缺少非诺贝酸胆碱的缓释剂型，现有的缓释制剂存在缓释效果不好等缺陷。
发明内容
本发明的目的是提供一种非诺贝酸胆碱的缓释胶囊的制备工艺及应用，该缓释胶囊在酸性环境几乎不释放，在水、pH6.8磷酸盐缓冲液、0.1mol/L盐酸液+pH6.8磷酸盐缓冲液中缓慢释放，10小时基本释放完全，且该缓释胶囊制备方法简单，易于实施。
本发明解决上述技术问题所采用的技术方案：
1)载药丸芯的制备：将非诺贝酸胆碱用3～5倍重量的乙醇溶解，将微晶纤维素空白丸芯加入流化床中，将非诺贝酸胆碱乙醇溶液喷到空白丸芯上，上药时控制雾化压力为2.5～3bar，蠕动泵转速为100～120rpm，物料温度为35～42℃，当非诺贝酸胆碱质量达到空白丸芯质量的50％时，停止上药，在65℃烘干2小时；
2)包薄膜衣：在流化床中向载药丸芯上喷入薄膜包衣剂，所述薄膜包衣剂的原料重量配比为乙基纤维素9％、葵二酸二丁酯1％、乙醇45％、异丙醇45％，控制薄膜包衣的雾化压力为2.5～3bar，蠕动泵转速为55～65rpm，物料温度为36～38℃，当载药丸芯增重1.5％时，停止包衣，65℃烘干12小时；
3)包肠溶衣：在流化床中向薄膜包衣的载药丸芯上喷入肠溶包衣剂，所述肠溶包衣剂的原料重量配比为L30D-55尤特奇20％、柠檬酸三乙酯2％、滑石粉10％、水68％，控制肠溶包衣的雾化压力为2.5～3bar，蠕动泵转速为45～50rpm，物料温度为30～35℃，当薄膜包衣的载药丸芯增重2％时，停止包衣，40℃烘干2小时；
4)过16～20目筛，填充入胶囊。
本发明制备的非诺贝酸胆碱的缓释胶囊与同类产品相比，释放速度更快，而且释放更加完全。
附图说明
图1是实施例1在pH6.8磷酸盐缓冲液中的释放曲线。
图2是实施例1在水中的释放曲线。
具体实施方式
下面通过实施例对本发明进行详细地说明。
实施例1
非诺贝酸胆碱缓释胶囊的制备方法，步骤如下：
1)载药丸芯的制备：将非诺贝酸胆碱用3倍重量的乙醇溶解，将微晶纤维素空白丸芯(购自德国JRS药用辅料公司)加入流化床中，将非诺贝酸胆碱乙醇溶液喷到空白丸芯上，上药时控制雾化压力为2.5～3bar，蠕动泵转速为100～120rpm，物料温度为35～42℃，当非诺贝酸胆碱质量达到空白丸芯质量的50％时，停止上药，在65℃烘干2小时；
2)包薄膜衣：在流化床中向载药丸芯上喷入薄膜包衣剂，所述薄膜包衣剂的原料重量配比为乙基纤维素9％、葵二酸二丁酯1％、乙醇45％、异丙醇45％，控制薄膜包衣的雾化压力为2.5～3bar，蠕动泵转速为55～65rpm，物料温度为36～38℃，当载药丸芯增重1.5％时，停止包衣，65℃烘干12小时；
3)包肠溶衣：在流化床中向薄膜包衣的载药丸芯上喷入肠溶包衣剂，所述肠溶包衣剂的原料重量配比为L30D-55尤特奇(甲基丙烯酸/丙烯酸乙酯＝1:1的共聚物，商品名为L30D-55尤特奇)20％、柠檬酸三乙酯2％、滑石粉10％、水68％，控制肠溶包衣的雾化压力为2.5～3bar，蠕动泵转速为45～50rpm，物料温度为30～35℃，当薄膜包衣的载药丸芯增重2％时，停止包衣，40℃烘干2小时；
4)过16-20目筛，填充入胶囊。
将实施例1制得的缓释胶囊与国外上市的同类样品分别在pH6.8磷酸盐缓冲液、水两种释放介质中进行了释放度对比试验，释放度曲线见图1和图2，从结果中可以看出，实施例1在磷酸盐缓冲液中的释放速度更快，而且释放更加完全；实施例1在水中4小时后的释放速度更快，而且释放更加完全。

Claims (1)

1.一种非诺贝酸胆碱缓释胶囊的制备方法，其特征在于包括以下步骤：
1)载药丸芯的制备：将非诺贝酸胆碱用3～5倍重量的乙醇溶解，将微晶纤维素空白丸芯加入流化床中，将非诺贝酸胆碱乙醇溶液喷到空白丸芯上，上药时控制雾化压力为2.5～3bar，蠕动泵转速为100～120rpm，物料温度为35～42℃，当非诺贝酸胆碱质量达到空白丸芯质量的50％时，停止上药，在65℃烘干2小时；
2)包薄膜衣：在流化床中向载药丸芯上喷入薄膜包衣剂，所述薄膜包衣剂的原料重量配比为乙基纤维素9％、葵二酸二丁酯1％、乙醇45％、异丙醇45％，控制薄膜包衣的雾化压力为2.5～3bar，蠕动泵转速为55～65rpm，物料温度为36～38℃，当载药丸芯增重1.5％时，停止包衣，65℃烘干12小时；
3)包肠溶衣：在流化床中向薄膜包衣的载药丸芯上喷入肠溶包衣剂，所述肠溶包衣剂的原料重量配比为L30D-55尤特奇20％、柠檬酸三乙酯2％、滑石粉10％、水68％，控制肠溶包衣的雾化压力为2.5～3bar，蠕动泵转速为45～50rpm，物料温度为30～35℃，当薄膜包衣的载药丸芯增重2％时，停止包衣，40℃烘干2小时；
4)过16～20目筛，填充入胶囊。
CN201610194181.5A 2016-03-31 2016-03-31 一种非诺贝酸胆碱缓释胶囊的制备方法 Pending CN105748445A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610194181.5A CN105748445A (zh) 2016-03-31 2016-03-31 一种非诺贝酸胆碱缓释胶囊的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610194181.5A CN105748445A (zh) 2016-03-31 2016-03-31 一种非诺贝酸胆碱缓释胶囊的制备方法

Publications (1)

Publication Number Publication Date
CN105748445A true CN105748445A (zh) 2016-07-13

Family

ID=56345475

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610194181.5A Pending CN105748445A (zh) 2016-03-31 2016-03-31 一种非诺贝酸胆碱缓释胶囊的制备方法

Country Status (1)

Country Link
CN (1) CN105748445A (zh)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070128278A1 (en) * 2005-04-08 2007-06-07 Ju Tzuchi R Pharmaceutical formulations
WO2010131265A1 (en) * 2009-05-11 2010-11-18 Lupin Limited Novel pharmaceutical compositions of choline fenofibrate
CN103211786A (zh) * 2012-01-18 2013-07-24 北京天衡药物研究院 胆碱非诺贝特膜控肠溶缓释微丸胶囊
CN104434847A (zh) * 2014-11-21 2015-03-25 哈尔滨圣吉药业股份有限公司 一种非诺贝酸胆碱缓释微丸及其制备方法
CN104721148A (zh) * 2013-12-18 2015-06-24 江苏豪森药业股份有限公司 肠溶缓释微丸或颗粒的固体制剂及其制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070128278A1 (en) * 2005-04-08 2007-06-07 Ju Tzuchi R Pharmaceutical formulations
WO2010131265A1 (en) * 2009-05-11 2010-11-18 Lupin Limited Novel pharmaceutical compositions of choline fenofibrate
CN103211786A (zh) * 2012-01-18 2013-07-24 北京天衡药物研究院 胆碱非诺贝特膜控肠溶缓释微丸胶囊
CN104721148A (zh) * 2013-12-18 2015-06-24 江苏豪森药业股份有限公司 肠溶缓释微丸或颗粒的固体制剂及其制备方法
CN104434847A (zh) * 2014-11-21 2015-03-25 哈尔滨圣吉药业股份有限公司 一种非诺贝酸胆碱缓释微丸及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
关世侠，等: "非诺贝特缓释微丸的制备及释放度研究", 《中国医院药学杂志》 *

Similar Documents

Publication Publication Date Title
AU2012388441B2 (en) Pharmaceutical or nutraceutical composition with sustained release characteristic and with resistance against the influence of ethanol
JP2021503463A (ja) コーティングされた硬カプセルを製造する方法
CA2653403C (en) Lipoic acid pellets
JP6695337B2 (ja) エタノールの影響に対する耐性を有する医薬品組成物または栄養機能食品組成物
KR20130099944A (ko) 하나 이상의 알긴산 염을 포함하는 위 내성 제약 또는 건강기능식품 제제
EP1748764A2 (en) An amine drug-containing slow-release granule preparation based on particles with a coating layer and the corresponding method of production
US9895318B2 (en) Pharmaceutical or nutraceutical composition with sustained release characteristic and with resistance against the influence of ethanol
CN101080218A (zh) 制备具有稳定的释放活性成分特性的包衣药物的方法
KR20100059912A (ko) 알리스키렌 및 발사르탄의 제약 조합물
CN104523654A (zh) 右兰索拉唑缓释胶囊及其制备方法
CA2986188A1 (en) Pharmaceutical or nutraceutical composition with resistance against the influence of ethanol
CN104434846A (zh) 盐酸二甲双胍肠溶缓释微丸及其制备方法
CN103211786B (zh) 胆碱非诺贝特膜控肠溶缓释微丸胶囊
CN105748445A (zh) 一种非诺贝酸胆碱缓释胶囊的制备方法
JP2007510655A (ja) バイオアベイラビリティーエンハンサを含む第四級アンモニウム化合物の組成物
CN104906077B (zh) 一种具有双相释药特性的非诺贝特酸胆碱盐控释制剂及其制备方法
CN105726488B (zh) 含有呼吸道合胞病毒抑制剂的肠溶微丸及其制备方法
CN103393615B (zh) 一种度洛西汀肠溶小丸及其制备方法
KR20100130882A (ko) 서방성 비스테로이드성 소염제 조성물 및 그 제조방법
WO2009066181A2 (en) Oral delayed-release duloxentine hydrochloride pellets
CN102579366A (zh) 一种依托贝特缓释微丸的制备方法
EP4072532B1 (en) Dosage form for use in treating or preventing of a disease
Andreazza et al. Preparation of pellets containing highly soluble drug by extrusion/spheronisation and coating with Kollicoat® SR 30D
CA3223775A1 (en) Composition comprising a (meth)acrylate copolymer, an alkali or ammonium salt of a saturated aliphatic monocarboxylic acid and specific glidants
CN115944602A (zh) 兰索拉唑肠溶微丸及其制备方法

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20160713

WD01 Invention patent application deemed withdrawn after publication