CN1777430B - 高载药美沙拉嗪小药囊 - Google Patents
高载药美沙拉嗪小药囊 Download PDFInfo
- Publication number
- CN1777430B CN1777430B CN2004800107906A CN200480010790A CN1777430B CN 1777430 B CN1777430 B CN 1777430B CN 2004800107906 A CN2004800107906 A CN 2004800107906A CN 200480010790 A CN200480010790 A CN 200480010790A CN 1777430 B CN1777430 B CN 1777430B
- Authority
- CN
- China
- Prior art keywords
- mesalazine
- preparation
- coating
- granule
- sachet
- 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.)
- Expired - Lifetime
Links
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 title claims description 54
- 229960004963 mesalazine Drugs 0.000 title claims description 54
- 239000003814 drug Substances 0.000 title claims description 16
- 229940079593 drug Drugs 0.000 title description 7
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- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 14
- 229920001249 ethyl cellulose Polymers 0.000 claims description 14
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 14
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- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 claims description 3
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
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- IQSHMXAZFHORGY-UHFFFAOYSA-N methyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound COC(=O)C=C.CC(=C)C(O)=O IQSHMXAZFHORGY-UHFFFAOYSA-N 0.000 description 1
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Landscapes
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Abstract
本发明涉及在易于生产和视觉吸引性方面具有所需特性的高载药制剂以及该制剂的小药囊。
Description
发明领域
本发明涉及一种包含高载量活性药物的药物制剂。
具体地说,本发明涉及口服给予含有5-氨基水杨酸(5-ASA,美沙拉明,美沙拉嗪)高载量(即具有高重量%活性药物)的药物制剂及其生产方法,以及用于制剂的小药囊.
本申请要求丹麦专利申请PA 200300612,欧洲专利申请EP 03388023和美国临时专利申请60/464649的优先权。
技术背景
已知含有美沙拉嗪的口服药物制剂为片剂或颗粒剂。颗粒剂可包装于小药囊中。对本发明而言,“小药囊”是指颗粒的封套或袋,而“颗粒”是指微粒、颗粒或滚圆的颗粒。
目前,已知含有250或500mg美沙拉嗪的片剂。通常,250mg片剂重量约为540mg,即它们的载药量为(250/450)重量%=46重量%。在题为“药物成分”的专利申请WO 00/44353中,描述了含有多达84重量%美沙拉嗪的片剂。
对于小药囊,Falk Pharma博士推出了一种产品,该产品声称在930mg小药囊中含有500mg美沙拉嗪,相当于载药量54重量%。
现今,处方中常常有多达4g的美沙拉嗪,用于每日治疗肠病如克罗恩病和溃疡性结肠炎。
如果以250mg片剂给予4g美沙拉嗪,患者需要一天吞咽16片。另一方面,可给予载药量在50%范围的500mg片剂,每片片剂重约1g,许多患者将感到吞咽困难。
这就需要提供一种能给予大的日剂量药物而不影响患者顺应性的产品。
已知以工业规模制造含有美沙拉嗪口服药物制剂的方法。然而,已知的制造方法需要大量生产步骤,以得到具有理想释放特征的产品。这就导致繁重且昂贵的制造。
发明内容
这些问题和其它下文提及的问题将通过本发明解决。
根据一方面,本发明涉及一种口服药物制剂,它包装于小药囊、、胶囊或泡罩型包装中,含有选自:55;60;65;70;75;80;85;90;92;94和96重量%的美沙拉嗪。根据优选的方面,该制剂含有92-98%,优选94-96重量%的美沙拉嗪。
这些方面提供了高载量的药物组合物。
就本发明而言,“美沙拉嗪”也包括其药学上可接受的盐和酯如在WO97/23199p.15,1.17-p.6,1.12中提及的盐和酯,以及前药如巴柳氮(balsalazide)。
制剂优选以颗粒状物质的形式,如颗粒、球、小丸、微粒,优选颗粒。
根据一方面,本发明涉及一种还包含药学上可接受的粘合剂、优选聚维酮的药物制剂,粘合剂的量选自1、2、3、4、5、6、7、8、9、10和12重量%。根据优选的方面,该制剂包含1-10,优选2-8,更优选3-7,优选4-6,最优选5重量%的聚维酮。
药学上可接受的粘合剂可包含任何可接受的粘合剂如阿拉伯胶、明胶、羟丙基纤维素、羟丙基甲基纤维素、甲基纤维素、聚乙二醇(PEG)、聚维酮、蔗糖、淀粉或任何这些物质的混合物。优选聚乙烯吡咯酮(聚烯吡酮,PVP)。
根据一方面,本发明涉及一种还包含包衣的药物制剂。包衣应优选包含释放修饰剂,如乙基纤维素、巴西棕榈蜡、虫胶或任何这些物质的混合物。优选乙基纤维素。
选择的包衣尤其取决于所需的释放形式。它可以选自限速的阻挡物质,例如肠或延迟包衣物质,如聚甲基丙烯酸酯,以Eudragits如Eudragit NE 40D或Eudragit L 100的形式市售。当使用半透性聚合物膜时,最优选的包衣是乙基纤维素。
根据一方面,该制剂是修饰的释放制剂,优选缓释制剂。
根据一方面,该制剂包含包衣,所述包衣对所述美沙拉嗪或所述药学上可接受的盐的重量比选自:0.1-10%、0.3-7%、0.5-5%、0.7-3%、0.8-2%和0.9-1.5%。可调节包衣的量,以达到所需的释放曲线。非常大量的包衣可阻碍活性成分的释放。
根据一方面,本发明涉及一种基本上包含美沙拉嗪、药学上可接受的粘合剂和包衣的药物制剂。
根据一方面,本发明涉及一种药物制剂,该制剂在模型系统中,使用美国药典桨法2(USP Paddle System 2),在37℃,100rpm搅拌下测定,以制剂中美沙拉嗪的总量计,该制剂具有240分钟后美沙拉嗪至少释放40,50,60,70,80或90%的体外释放特征。通常,优选较高的释放,以保证肠中的有效释放。
根据一方面,本发明涉及一种药物制剂,该制剂在模型系统中,使用美国药典桨法2,在37℃,100rpm搅拌下测定制剂中美沙拉嗪的总量,美沙拉嗪的体外释放特征为:
a)15分钟后释放5-25%;
b)90分钟后释放30-70%,优选40-60%;和
c)240分钟后释放75-100%;
模型系统的溶出度参数为:溶出介质:1000ml去气的0.1M硫酸钠缓冲液pH7.5。
装置:美国药典23桨法(装置2)
轴旋转速度:100rpm。1g小药囊用于实验。
根据第一优选的方面,本发明涉及一种药物制剂,该制剂的相似性系数f2与标准制剂相比,高于选自25,30,35,40,45,50,55,60,65和70的数字,其美沙拉嗪的体外释放特征为
a)15分钟后释放12%;
b)90分钟后释放50%;
c)240分钟后释放85%;
在上文列出的条件下测定。
相似性系数f2的定义为
其中,n是时间点的数字,R(t)是标准制剂活性成分的平均溶出百分数,T(t)是本发明制剂活性成分的平均溶出百分数。通常,认为满意的相似性系数的范围为50-100,但为了本发明的目的,相似系数甚至可更小。
根据第二优选的方面,本发明涉及一种药物制剂,该制剂的相似性系数f2与标准制剂相比,高于选自25,30,35,40,45,50,55,60,65和70的数字,其美沙拉嗪的体外释放特征为
a)15分钟后释放21%;
b)90分钟后释放68%;
c)240分钟后释放94%;
在上文列出的条件下测定。
根据一方面,本发明涉及一种药物制剂,所述药物制剂包装于小药囊中。
根据一方面,本发明涉及一种制备颗粒的方法,包括以下步骤:
a)美沙拉嗪与造粒液混合;
b)通过制粒、压制或挤压得到颗粒;
c)干燥颗粒;
d)按需调节颗粒的大小;
e)按需筛分颗粒;
其特征在于以下附加步骤:
f)颗粒包衣;
任选地还包括:
g)筛分包衣的颗粒;
h)空气吹扫包衣的颗粒,和
i)把包衣颗粒包装于小药囊、胶囊或泡罩型包装中。
根据一方面,本发明涉及一种方法,其中,包衣的颗粒包装于小药囊中。
本方法提供一种药物制剂简单的制造方法。
根据本发明的一方面,提供了一种没有滚圆生产的药物组合物。因而,该组合物无需滚圆就可得到。因此,不需要滚圆助剂,以使药物组合物具有高载药量。
已使用滚圆在工业规模上得到可重复产品,该产品视觉上吸引人,易于服用,因而患者顺应性高。
在本发明以前,都认为必需滚圆美沙拉嗪药物,以得到视觉上吸引人和易于服用的小药囊产品。滚圆涉及使用滚圆助剂或增强剂如微晶纤维素。滚圆助剂的存在使载药量比用本发明可得到的载药量低。
存在需要不含杂质的高载量的药物组合物。根据本发明的一方面不经滚圆得到满足这些标准的药物制剂。该组合物可通过得到的颗粒提供。颗粒可通过制粒、压制或挤压得到,以得到一种对于给予所述药物制剂的人来说,视觉上吸引人的产品。可进行压制,如通过轧辊压制。优选通过挤压得到颗粒。
根本发明的某些优选方面,可根据题为“含5-氨基水杨酸的药物制剂的制备方法用于治疗溃疡性结肠炎和克罗恩病”(″Method for the preparationof a pharmaceutical composition comprising 5-aminosalicylic acid for use intreatment of Ulcerative Colitis and Crohn′s Disease″)的共同待批专利申请PCT/DK01/00677改进得到药物组合物。改进包括包衣应根据本发明调节,包衣后,过筛和氮气吹扫,所得颗粒包装于小药囊中,无需其它赋形剂(比较实施例3和所述申请图4)。尤其优选造粒液包含至少50%,更优选60%,优选70%,更优选80%,优选85%,更优选90%w/w水。
根据一方面,本发明涉及方法,其中,造粒液包括溶解于水中的聚维酮。
根据一方面,本发明涉及方法,其中,所述干燥步骤c)在流化床干燥炉中进行。
根据一方面,本发明涉及方法,其中,所述粒度调节步骤d)通过碾磨进行。
根据一方面,本发明涉及方法,其中,过筛步骤e)选择通过1.8mm筛但不能通过0.5mm筛的颗粒进行。
可使用其它合适的筛子,例如筛目孔径选自4.0、3.15、2.5、2.0、1.8、1.6、1.4、1.25、1.18、1.0、0.9、0.8、0.71、0.6、0.5和0.4mm,用于选择所需颗粒。可选择筛子以确定粒径的上和/或下限。
根据另一方面,碾磨后所得颗粒具有通过筛分析测定的粒径分布,主要部分为850μm-1000μm。可改变挤压机中的孔以得到所需粒径。根据一方面,超过75%,优选超过85%,最优选超过90%的颗粒粒径为850μm-1000μm。
根据一方面,本发明涉及方法,其中,包衣步骤f)采用乙基纤维素。
根据一方面,本发明涉及方法,其中,包衣步骤f)通过以下步骤进行:用一定量的包衣材料喷洒,包衣材料的量根据比表面积调节,在0.09-0.17mg/cm2范围内,优选0.11-0.15mg/cm2,更优选0,12-0,14mg/cm2,然后干燥。已发现这些量适合用乙基纤维素包衣。
已发现,可通过根据比表面积调节所用包衣材料的量,得到所需的释放曲线。
根据“表面积测量粗颗粒物质的渗透测定技术的评价”(Evaluation ofa permeametry technique for surface area measurement of coarse particulatematerials),International Journal of Pharmaceutics,Eriksson等,1990,63,189-199页”的渗透测定法测定比表面积。
根据共同待批专利申请PCT/DK01/00677得到的颗粒,优选根据本发明改进,尤其优选具有光滑表面以利于测量比表面积和后续的包衣。
为了能确定应用于颗粒包衣的量,测定了表面积。在每表面积包衣的量与溶出速率分布间的测量相关性的基础上,可从颗粒的测定表面积预测所需包衣的量。通过反复试验,如取决于所用确切条件如装置和辅料来调整量。
根据一方面,本发明涉及方法,其中,过筛步骤g)在旋转筛上进行,优选筛目大小2.5mm,以得到粒度小于或等于2.5mm的包衣颗粒。
可使用其它合适的筛,如筛目大小选自4.0、3.15、2.5、2.0、1.8、1.6、1.4、1.25、1.18、1.0、0.9、0.8、0.71、0.6、0.5和0.4mm,以选择所需包衣颗粒的尺寸。
根据一方面,本发明涉及一种根据本方法得到的药物制剂,优选根据上述任一方面。
根据一方面,本发明涉及医用的药物制剂。
根据一方面,本发明涉及使用美沙拉嗪以制造根据本发明的药物制剂,包含美沙拉嗪的总量选自0.5g、1.0g、1.5g、2g、3g、4g、5g、6g、8g、和10g。
根据一方面,本发明涉及用途,其中,药物用于治疗肠病(intestinalbowel disease(IBD)),尤其是克罗恩病或溃疡性结肠炎。
根据本发明的制剂适用于治疗IBD。
根据一方面,本发明涉及一种治疗IBD的方法,其中,本发明制剂给予患者,优选每天1、2、3或4次。
本发明制剂包装于向患者给药的不同的容器中,即胶囊、泡罩型包装、或小药囊中。
根据一方面,本发明涉及本发明药物制剂的小药囊。
本小药囊可用于任何药物制剂,但尤其适用于储存含有敏感化合物如美沙拉嗪的药剂。
根据一方面,本发明涉及一种小药囊,包括下面的层:
i)纸;
ii)粘合层,优选粘合剂如聚乙烯;
iii)阻挡层,优选铝箔;和
iv)密封层,优选低密度聚乙烯。
美沙拉嗪对湿度、大气和/或光敏感。因此,含有美沙拉嗪的产品小药囊应优选能阻挡湿度、大气和光。小药囊还应能易于患者打开,优选无需使用附加工具如剪刀。提供具有必要阻挡性能、用手指撕开小药囊而没有撕破的可能性是一个问题。而且,现有小药囊会因静电的产生而受到损害。优选地,小药囊应易于制造,易于填充和清空,并具有吸引人的外观以改善患者顺应性。
该方面提供使所含的药物组合物以长期储存稳定性的小药囊,例如活性药物成分是美沙拉嗪。而且,该小药囊容易撕开并消除了静电,提供能完全清空其内容物的小药囊。本发明小药囊和口服制剂的组合几乎没有静电产生。
根据一方面,本发明涉及小药囊,其中,粘合层ii)的重量/单位面积优选为6-20g/m2,优选9-15g/m2,更优选12g/m2;阻挡层iii)的厚度优选为6-30μm,更优选7-25μm,优选9-25μm,更优选8-20μm,优选9-15μm,更优选12μm;和/或密封层iv)的重量/单位面积优选为10-100g/m2,更优选15-75g/m2,优选20-50g/m2,更优选30-40g/m2,最优选35g/m2。
在一个优选的实施例中,外面的纸i)的重量/单位面积为10-100g/m2,优选30-70g/m2,最优选50g/m2。
根据一方面,本发明涉及本发明小药囊用于药物组合物。
已证明本发明小药囊适用于储存药物组合物。
根据一方面,本发明涉及小药囊用于医学目的。
根据本发明的一方面,本发明并不限于美沙拉嗪用作活性成分,它还涉及其它活性成分如WO 00/44353,12-16页中提到的成分。其它低效活性成分适用于本发明。尤其预想布洛芬代替美沙拉嗪。
根据本发明的一方面,本发明组合物中可包含其它辅料,如填充剂、崩解剂、pH调节剂或表面活性剂。这种辅料从文献中熟知,例如,参见WO 00/44353,16-20页中许多合适的辅料。
实施方式
除非另有说明,所有百分比是重量百分比。
实施例1
下面提供了180000个延长释放颗粒的小药囊的批量生产。
组成 | 量 | 规格 |
美沙拉嗪 | 180kg | Ferring |
聚维酮 | 9kg | 欧洲药典 |
纯化的水 | 33.3kg** | 欧洲药典 |
乙基纤维素 | 1.9kg*** | 欧洲药典 |
丙酮 | 188kg** | 欧洲药典 |
**生产中蒸发
***调节乙基纤维素的量,以保证成品所需的溶出度分布。
欧洲药典是指在本申请提交时当前的版本。
制造方法密切地按照共同待批专利申请PCT/DK01/00677所描述的制造方法,仅有一些例外。调节成分的量和类型,尤其是降低乙基纤维素的量,以得到所需的溶出度分布。在本实施例中,不制备片剂,所以不包括用于此目的辅料,空气吹扫后不进行干混合,不进行压片。因此,本方法得到的颗粒产品与所述应用的片剂不同。
制剂的制造方法可分为9个步骤:
1.制备成粒液
2.美沙拉嗪与水和PVP制粒
3.挤压
4.流化床干燥
5.碾磨
6.筛分
7.包衣
8.筛分
9.空气吹扫
生产设备 作用
NICA挤压机E220 挤压
Rotostat T05 混合
NIRO流化床干燥机 干燥
Quadro Comil U10 碾磨
Mogensen筛分机 筛分
Hüttlin Kugelcoater HKC 400 包衣
Prodima旋转筛分机 筛分
吹扫装置 空气吹扫
步骤1:
对于一批造粒液,将水装入Müller圆筒中。混合机置于适当位置并启动。在水上缓慢喷洒聚乙烯吡咯烷酮(PVP),使混合机运转固定时间直到所有PVP溶解。
步骤2和3:
将美沙拉嗪置于振荡的Prodima料斗中,使用传送机将美沙拉嗪转运至载重带给料机,将美沙拉嗪加到连续的Niro生产线上。在Niro生产线的第一部分,混合美沙拉嗪和PVP的水溶液成湿物质后,转运至挤压机中。挤压美沙拉嗪和PVP/水的湿物质通过筛目0.9mm后,颗粒直接进入流化床干燥机。
步骤4:
流化床干燥机分为两个主要部分。在第一个部分中,干燥颗粒的表面以防止它们粘附在一起。在流化床的这部分中,随机混合颗粒。一些停留时间后,将颗粒移入干燥机的第二部分,进行实际的干燥。在干燥机的的第二部分中,利用干燥空气通过干燥机来引导颗粒(鱼鳃板中孔的特殊图案)。当颗粒干燥时,使它们进入置于流化床下面的圆筒中。流化床是以这样的方式构造的,即流化床中总的停留时间约为21/2小时。
步骤5:
将含有干颗粒的圆筒倒置于碾磨机的顶部,并用筛子轻轻碾磨颗粒,这仅仅是使太长的颗粒断裂。通过碾磨机后,使颗粒进入圆筒中。
步骤6:
因为碾磨过程产生了少量尺寸过小的颗粒,所以使用Mogensen振荡筛分机筛分颗粒。弃去通过0.8mm筛目的颗粒,或收集后储存于不透气的贴有标签的容器中用于再处理。
步骤7:
在Kugel包衣机(流化床系统)中,用包括溶解于丙酮的乙基纤维素的包衣液,对200kg筛分过的颗粒进行包衣。
为了能确定应用于颗粒以得到所需溶出速率分布所必需的乙基纤维素的正确量,在包衣过程前测定颗粒的表面积。基于包衣量/表面积与颗粒的溶出速率之间具有相关性,因而对应用于颗粒所必需的包衣量已作了预测。
当包衣步骤在HKC 400Hüttlin Kugel包衣机中进行且接着进行生产规模的筛分时,将乙基纤维素的量调节至0.13mg/cm2,根据本发明或根据由相似性因素所定义的第一个优选的方面,通过测定美沙拉嗪总量的释放%得到释放特征。
包衣过程结束后,包衣颗粒装载入圆筒中,用于进一步加工。
步骤8:
包衣过程结束后,在Prodima旋转筛分机中筛分包衣颗粒。弃去大块。
步骤9:
筛分该批包衣颗粒后,将它们分成两个圆筒,用压缩空气或氮气吹扫。吹扫颗粒6-14小时。此吹扫过程是必需的,以降低包衣颗粒中残留溶剂(丙酮)的量。
该批具有下列大致成分的颗粒:
美沙拉嗪 94.3%
聚维酮 4.7%
乙基纤维素 1.0%
然后,将颗粒填充入小药囊中。
小药囊的材料具有以下成分:
粘土覆盖的纸 50g/m2
低密度聚乙烯 12g/m2
铝箔 12μm
低密度聚乙烯 35g/m2
本实施例中,12g/m2PE相当于13μm,35g/m2PE相当于38μm。材料具有克重为129g/m2。水蒸气渗透性<0.05g/m2,24h,25℃,75%相对湿度,O2<0.05ml/m2,24h,大气,23℃,75%相对湿度。
小药囊围绕填充/密封装置的填料管卷起,以使纸在小药囊的外部,然后,用低密度聚乙烯纵向密封作为密封层。底部横向密封形成后,用颗粒填充小药囊,然后再次密封顶部,最后切割。
所有引用的全部内容参考包括于此。
Claims (20)
1.一种颗粒形式的口服药物制剂,其含有
92-98重量%的美沙拉嗪或其药学上可接受的盐,和
-2-8重量%的聚维酮,
其中所述制剂还包含含有释放修饰剂的包衣并且包装于小药囊、胶囊或泡罩型包装中。
2.如权利要求1所述的药物制剂,其特征在于,在采用美国药典桨法2、在37℃操作并以100rpm搅拌的模型系统中测定,以制剂中美沙拉嗪的总量计,所述制剂具有240分钟后美沙拉嗪至少释放40%的体外释放特征。
3.如权利要求1或2所述的药物制剂,其特征在于,在采用美国药典桨法2、在37℃操作并以100rpm搅拌的模型系统中测定,所述制剂具有以下美沙拉嗪的体外释放特征:
a)15分钟后释放5-25%;
b)90分钟后释放30-70%;和
c)240分钟后释放75-100%;
制剂中美沙拉嗪的总量。
4.如权利要求3所述的药物制剂,其特征在于,所述制剂的相似性系数f2与标准制剂相比高于30,在权利要求3所述的条件下测定,所述制剂具有以下美沙拉嗪的体外释放特征:
a)15分钟后释放12%;
b)90分钟后释放50%;和
c)240分钟后释放85%;
5.如权利要求1所述的药物制剂,其特征在于,所述包衣含有乙基纤维素或由乙基纤维素组成。
6.如权利要求1所述的药物制剂,其特征在于,所述包衣与所述美沙拉嗪或其药学上可接受的盐的重量比选自:0.1-10%、0.3-7%、0.5-5%、0.7-3%、0.8-2%和0.9-1.5%。
7.如权利要求1所述的药物制剂,其特征在于,由美沙拉嗪、聚维酮和包衣组成。
8.上述权利要求任一项所述的药物制剂的制造方法,包括以下步骤:
a)将美沙拉嗪与造粒液混合,所述的造粒液包含聚维酮;
b)通过制粒、压制或挤压得到颗粒;
c)干燥颗粒;
d)按需调节颗粒的大小;和
e)按需筛分颗粒;
其特征在于以下附加步骤:
f)颗粒包衣;
并任选包括:
g)筛分包衣颗粒;
h)空气吹扫包衣颗粒;
还包括:
i)把包衣颗粒包装于小药囊、胶囊或泡罩型包装中。
9.如权利要求8所述的方法,其特征在于,所述造粒液由溶解于水的聚维酮构成。
10.如权利要求8或9所述的方法,其特征在于,所述干燥步骤c)在流化床干燥机中进行。
11.如权利要求8所述的方法,其特征在于,所述调节颗粒大小的步骤d)在碾磨机中进行。
12.如权利要求8所述的方法,其特征在于,所述筛分步骤e)通过选择能通过1.8mm筛但不能通过0.5mm筛的颗粒来进行。
13.如权利要求8所述的方法,其特征在于,所述包衣步骤f)使用乙基纤维素进行。
14.如权利要求8所述的方法,其特征在于,所述包衣步骤f)根据比表面积调节包衣材料用量,包衣材料用量在0.09-0.17mg/cm2范围内,然后干燥。
15.如权利要求14所述的方法,其特征在于,所述包衣步骤f)根据比表面积调节包衣材料用量,包衣材料用量在0.11-0.15mg/cm2范围内,然后干燥。
16.如权利要求8所述的方法,其特征在于,所述筛分步骤g)在旋转筛分机上进行。
17.如权利要求16所述的方法,其特征在于,所述筛分步骤g)以筛目大小为2.5mm进行。
18.美沙拉嗪在制造如权利要求1-7中任一项所述的药物制剂中的应用,所述制剂包含美沙拉嗪的总剂量选自以下:0.5g、1.0g、1.5g、2g、3g、4g、5g、6g、8g和10g;所述的药物制剂包装于小药囊、胶囊或泡罩型包装中。
19.如权利要求18所述的应用,其特征在于,所述药物用于治疗肠病。
20.如权利要求19所述的应用,其特征在于,所述的肠病是克罗恩病或溃疡性结肠炎。
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Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6632429B1 (en) | 1999-12-17 | 2003-10-14 | Joan M. Fallon | Methods for treating pervasive development disorders |
US8030002B2 (en) | 2000-11-16 | 2011-10-04 | Curemark Llc | Methods for diagnosing pervasive development disorders, dysautonomia and other neurological conditions |
AR036797A1 (es) | 2001-10-15 | 2004-10-06 | Ferring Bv | Un metodo para preparar una composicion farmaceutica que comprende acido 5-aminosalicilico para utilizar en el tratamiento de colitis ulcerosa y enfermedades de crohn |
EP1615619A2 (en) | 2003-04-23 | 2006-01-18 | Ferring B.V. | Sachet for a pharmaceutical composition |
US20080058282A1 (en) | 2005-08-30 | 2008-03-06 | Fallon Joan M | Use of lactulose in the treatment of autism |
US7951436B2 (en) | 2006-08-14 | 2011-05-31 | Frito-Lay North America, Inc. | Environmentally-friendly multi-layer flexible film having barrier properties |
US7943218B2 (en) | 2006-08-14 | 2011-05-17 | Frito-Lay North America, Inc. | Environmentally-friendly multi-layer flexible film having barrier properties |
US7645801B2 (en) * | 2007-01-29 | 2010-01-12 | Alaven Pharmaceutical Llc | Reduced irritant enema for treatment of inflammatory bowel disease (IBD) |
US20090169622A1 (en) * | 2007-12-27 | 2009-07-02 | Roxane Laboratories, Inc. | Delayed-release oral pharmaceutical composition for treatment of colonic disorders |
US8658163B2 (en) | 2008-03-13 | 2014-02-25 | Curemark Llc | Compositions and use thereof for treating symptoms of preeclampsia |
WO2009118761A2 (en) * | 2008-03-24 | 2009-10-01 | Bhandari Mohan Harakchand | Metallized paper based lidding material for blister packaging & process thereof |
US8084025B2 (en) | 2008-04-18 | 2011-12-27 | Curemark Llc | Method for the treatment of the symptoms of drug and alcohol addiction |
US9320780B2 (en) | 2008-06-26 | 2016-04-26 | Curemark Llc | Methods and compositions for the treatment of symptoms of Williams Syndrome |
ES2732453T3 (es) | 2008-07-01 | 2019-11-22 | Curemark Llc | Métodos y composiciones para el tratamiento de síntomas de trastornos neurológicos y de salud mental |
US10776453B2 (en) | 2008-08-04 | 2020-09-15 | Galenagen, Llc | Systems and methods employing remote data gathering and monitoring for diagnosing, staging, and treatment of Parkinsons disease, movement and neurological disorders, and chronic pain |
US20100092447A1 (en) | 2008-10-03 | 2010-04-15 | Fallon Joan M | Methods and compositions for the treatment of symptoms of prion diseases |
NZ592049A (en) * | 2008-10-03 | 2012-11-30 | Falk Pharma Gmbh | Compositions and methods for the treatment of bowel diseases with granulated mesalamine |
WO2010080835A1 (en) | 2009-01-06 | 2010-07-15 | Curemark Llc | Compositions and methods for the treatment or the prevention oral infections by e. coli |
AU2010203709B2 (en) | 2009-01-06 | 2014-05-22 | Galenagen, Llc | Compositions and methods for the treatment or prevention of Staphylococcus Aureus infections and for the Eradication or reduction of Staphylococcus Aureus on surfaces |
US9056050B2 (en) * | 2009-04-13 | 2015-06-16 | Curemark Llc | Enzyme delivery systems and methods of preparation and use |
US9511125B2 (en) | 2009-10-21 | 2016-12-06 | Curemark Llc | Methods and compositions for the treatment of influenza |
EP2340812A1 (en) | 2009-12-18 | 2011-07-06 | Ferring International Center S.A. | Granules for pharmaceutical preparations, methods and apparatus for their production |
CN103153944A (zh) * | 2010-09-10 | 2013-06-12 | 法莫再尔公司 | 晶态5-氨基水杨酸的制备方法 |
DK2701733T3 (da) | 2011-04-21 | 2019-05-27 | Curemark Llc | Forbindelser til behandling af neuropsykiatriske forstyrrelser |
US9040120B2 (en) | 2011-08-05 | 2015-05-26 | Frito-Lay North America, Inc. | Inorganic nanocoating primed organic film |
US9267011B2 (en) | 2012-03-20 | 2016-02-23 | Frito-Lay North America, Inc. | Composition and method for making a cavitated bio-based film |
US9162421B2 (en) | 2012-04-25 | 2015-10-20 | Frito-Lay North America, Inc. | Film with compostable heat seal layer |
US10350278B2 (en) | 2012-05-30 | 2019-07-16 | Curemark, Llc | Methods of treating Celiac disease |
AU2013278072B2 (en) | 2012-06-23 | 2016-03-17 | Frito-Lay North America, Inc. | Deposition of ultra-thin inorganic oxide coatings on packaging |
US9090021B2 (en) | 2012-08-02 | 2015-07-28 | Frito-Lay North America, Inc. | Ultrasonic sealing of packages |
US9149980B2 (en) | 2012-08-02 | 2015-10-06 | Frito-Lay North America, Inc. | Ultrasonic sealing of packages |
CN102784154B (zh) * | 2012-09-01 | 2013-10-09 | 朱文军 | 一种美沙拉嗪肠溶片及其制备方法 |
WO2015159302A2 (en) * | 2014-04-17 | 2015-10-22 | Athena Drug Delivery Solutions Pvt Ltd. | Process for preparation of mesalamine composition and mesalamine composition thereof |
EP3154523B1 (en) * | 2014-06-16 | 2018-11-21 | Valpharma International S.P.A. | Formulation for oral administration containing mesalazine |
EP3162362A1 (de) | 2015-10-30 | 2017-05-03 | Dr. Falk Pharma Gmbh | Optimierte mesalazinhaltige hochdosistablette |
US11602512B1 (en) | 2016-07-22 | 2023-03-14 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11986451B1 (en) | 2016-07-22 | 2024-05-21 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11602513B1 (en) | 2016-07-22 | 2023-03-14 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
UY37341A (es) | 2016-07-22 | 2017-11-30 | Flamel Ireland Ltd | Formulaciones de gamma-hidroxibutirato de liberación modificada con farmacocinética mejorada |
WO2019123269A1 (en) * | 2017-12-20 | 2019-06-27 | Flamel Ireland Limited | Packaged modified release gamma-hydroxybutyrate formulations having improved stability |
TR201722852A2 (tr) | 2017-12-29 | 2019-07-22 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Mesalazi̇ni̇n oral farmasöti̇k kompozi̇syonlari |
US11541009B2 (en) | 2020-09-10 | 2023-01-03 | Curemark, Llc | Methods of prophylaxis of coronavirus infection and treatment of coronaviruses |
WO2022129003A1 (en) | 2020-12-15 | 2022-06-23 | Dsm Ip Assets B.V. | Multiparticulate solid oral dosage form comprising statin and vitamin e |
US11779557B1 (en) | 2022-02-07 | 2023-10-10 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1207672A (zh) * | 1995-12-21 | 1999-02-10 | 药物实验室费林公司 | 含有5-asa的控释口服药物组合物及其治疗肠道疾病的方法 |
Family Cites Families (67)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4638131B1 (zh) | 1966-06-22 | 1971-11-10 | ||
US4085244A (en) * | 1976-02-10 | 1978-04-18 | Champion International Corporation | Balanced orientated flexible packaging composite |
US4360550A (en) * | 1979-09-12 | 1982-11-23 | Toyo Kagaku Kabushiki Kaisha | Composite packing film and packing bag made of the same |
US4960765A (en) | 1980-03-20 | 1990-10-02 | Farmaceutisk Laboratorium Ferring A/S | Pharmaceutical composition and method for the treatment of colitis ulcerosa and Crohn's disease by oral administration |
WO1981002671A1 (en) | 1980-03-20 | 1981-10-01 | Ferring Farma Lab | Pharmaceutical composition and method for the treatment of colitis ulcerosa and crohn's disease by oral administration |
JPS6048484B2 (ja) | 1980-05-20 | 1985-10-28 | アルザ・コ−ポレ−シヨン | 拡散性活性剤デイスペンサ− |
JPS5758631A (en) | 1980-09-24 | 1982-04-08 | Toyo Jozo Co Ltd | Coating composition |
ZA825384B (en) | 1981-07-31 | 1983-05-25 | Tillott J B Ltd | Orally administrable pharmaceutical compositions |
US4418841A (en) * | 1982-11-23 | 1983-12-06 | American Can Company | Multiple layer flexible sheet structure |
DE3151196A1 (de) | 1981-12-23 | 1983-06-30 | Kurt Heinz Prof. Dr. 7800 Freiburg Bauer | Verfahren zur herstellung von gut loeslichen 5-aminosalicylsaeure-arzneimittelzubereitungen |
US4629657A (en) * | 1982-12-13 | 1986-12-16 | Enron Chemical Company | Biaxially oriented polypropylene film construction for special lamination |
US4489112A (en) * | 1983-03-28 | 1984-12-18 | Ex-Cell-O Corporation | Laminated paperboard container with absorption resistance means, and blank for constructing same |
SE457505B (sv) | 1984-01-10 | 1989-01-09 | Lejus Medical Ab | Laminatbelagd oral farmaceutisk komposition och foerfarande foer dess framstaellning |
NL8502178A (nl) | 1984-08-16 | 1986-03-17 | Sandoz Ag | Nieuwe farmaceutische preparaten. |
US4693395A (en) * | 1984-12-28 | 1987-09-15 | Colgate-Palmolive Company | Ethylene propylene copolymer in a substrate and collapsible dispensing container made therefrom |
US4702905A (en) * | 1985-08-30 | 1987-10-27 | Colgate-Palmolive Company | Packaged dental cream |
US4705680A (en) * | 1986-01-22 | 1987-11-10 | Colgate-Palmolive Company | Stable dental cream in polyethylene or polypropylene container |
US4720473A (en) | 1986-03-10 | 1988-01-19 | Cri International, Inc. | Production of improved catalyst-type particles using length and density grading |
FR2600893B1 (fr) * | 1986-07-01 | 1990-01-12 | Sandoz Lab | Nouvelles compositions pharmaceutiques a base de sels de calcium |
US5254347A (en) | 1988-03-31 | 1993-10-19 | Tanabe Seiyaku Co., Ltd. | Controlled release pharmaceutical preparation and method for producing the same |
US5194464A (en) * | 1988-09-27 | 1993-03-16 | Takeda Chemical Industries, Ltd. | Enteric film and preparatoin thereof |
US5484605A (en) | 1988-11-25 | 1996-01-16 | Henning Berlin Gmbh Chemie-Und Pharmawerk | Agent for treating chronically inflammatory intestinal diseases |
GB8828349D0 (en) * | 1988-12-05 | 1989-01-05 | Du Pont Canada | Film laminate with easy to td tear |
GB8913889D0 (en) | 1989-06-16 | 1989-08-02 | May & Baker Ltd | New compositions of matter |
IT1246382B (it) | 1990-04-17 | 1994-11-18 | Eurand Int | Metodo per la cessione mirata e controllata di farmaci nell'intestino e particolarmente nel colon |
GB2253346A (en) * | 1991-02-22 | 1992-09-09 | John Rhodes | Delayed release oral dosage forms for treatment of intestinal disorders |
US5433982A (en) * | 1990-11-14 | 1995-07-18 | Dai Nippon Printing Co., Ltd. | Composite container having barrier property |
US5316772A (en) * | 1990-12-19 | 1994-05-31 | Solvay & Cie, S.A. (Societe Anonyme) | Bilayered oral pharmaceutical composition with pH dependent release |
GB2256587A (en) | 1991-06-11 | 1992-12-16 | American Cyanamid Co | Acetazolamide in sustained release form |
US5472712A (en) | 1991-12-24 | 1995-12-05 | Euroceltique, S.A. | Controlled-release formulations coated with aqueous dispersions of ethylcellulose |
US5474818A (en) * | 1992-05-15 | 1995-12-12 | International Paper | Flexible container with nonstick interior |
JP2607422B2 (ja) * | 1992-09-08 | 1997-05-07 | 呉羽化学工業株式会社 | 内服用吸着剤の分包包装体及びその製造方法 |
JPH0827133B2 (ja) | 1993-07-13 | 1996-03-21 | 不二パウダル株式会社 | 湿潤粉粒体の処理装置 |
US5482718A (en) | 1994-03-23 | 1996-01-09 | Hoffmann-La Roche Inc. | Colon-targeted delivery system |
JPH0880597A (ja) * | 1994-07-14 | 1996-03-26 | Kyodo Printing Co Ltd | 抗菌性積層体、これを用いた袋体、容器および成形カップ |
JPH0826977A (ja) | 1994-07-19 | 1996-01-30 | Tanabe Seiyaku Co Ltd | 溶出制御型経口製剤 |
IT1277663B1 (it) * | 1995-09-28 | 1997-11-11 | Crinos Industria Farmaco | Sospensioni acquose stabili di mesalazina per uso topico |
US6004581A (en) | 1995-12-21 | 1999-12-21 | Farmaceutisk Laboratorium Ferring A/S | Modified release oral pharmaceutical composition and method for the treatment of bowel diseases |
US6245351B1 (en) | 1996-03-07 | 2001-06-12 | Takeda Chemical Industries, Ltd. | Controlled-release composition |
IL118932A0 (en) | 1996-07-24 | 1996-10-31 | Dexcel Ltd | Controlled release tablets |
JP2002511774A (ja) | 1996-07-28 | 2002-04-16 | バイオセンス・インコーポレイテッド | 電磁的心臓生体刺激法 |
WO1998026767A2 (en) | 1996-12-17 | 1998-06-25 | Poli Industria Chimica S.P.A. | Site-specific controlled release dosage formulation for mesalamine |
GB9722426D0 (en) | 1997-10-23 | 1997-12-24 | Univ London Pharmacy | Controlled release formulations |
EP0939037A1 (de) * | 1998-02-26 | 1999-09-01 | Alusuisse Technology & Management AG | Verpackungsmaterial |
US6194465B1 (en) | 1998-05-19 | 2001-02-27 | Centaur Pharmaceuticals, Inc. | Benzamide therapeutics for the treatment of inflammatory bowel disease |
ATE553919T1 (de) * | 1998-09-03 | 2012-05-15 | Stora Enso Ab | Papier-oder kartonlaminat und verfahren zu seiner herstellung |
CO5140079A1 (es) * | 1998-10-14 | 2002-03-22 | Novartis Ag | Composicion farmaceutica de liberacion sostenida y metodo para liberar un agente farmaceuticamente activo de liberacion sostenida y metodo para liberar un agente far- maceuticamente activo |
IT1303753B1 (it) * | 1998-11-13 | 2001-02-23 | Ct Lab Farm Srl | Composizioni farmaceutiche somministrabili per via orale contenentiun rivestimento gastroresistente a base di polimeri acrilici. |
WO2000044353A1 (de) | 1999-01-29 | 2000-08-03 | Losan Pharma Gmbh | Pharmazeutische zusammensetzungen |
ITMI991316A1 (it) * | 1999-06-14 | 2000-12-14 | Cip Ninety Two 92 S A | Composizioni farmaceutiche orali a rilascio modificato di mesalazina |
JP2001055322A (ja) | 1999-08-18 | 2001-02-27 | Tanabe Seiyaku Co Ltd | パルス放出型製剤 |
JP4439629B2 (ja) * | 1999-09-14 | 2010-03-24 | 久光製薬株式会社 | 包装用袋体 |
US6199698B1 (en) * | 1999-12-03 | 2001-03-13 | Alusuisse Technology & Management, Ltd. | Pharmaceutical packaging with separation means |
US6627223B2 (en) | 2000-02-11 | 2003-09-30 | Eurand Pharmaceuticals Ltd. | Timed pulsatile drug delivery systems |
IT1318376B1 (it) | 2000-03-07 | 2003-08-25 | Pharmatec Internat S R L | Forme solide orali a rilascio controllato contenenti mesalazina comeprincipio attivo. |
DE10013030A1 (de) | 2000-03-17 | 2001-09-20 | Roehm Gmbh | Verwendung eines Copolymers zur Herstellung einer Arzneiform zur Therapie von Colitis ulcerosa und verwendungsgemäße Arzneiform |
IT1318625B1 (it) * | 2000-07-14 | 2003-08-27 | Roberto Valducci | Formulazioni farmaceutiche solide orali a rilascio multifasicoph-dipendente. |
JP2004507487A (ja) * | 2000-08-29 | 2004-03-11 | メファ・アクチェンゲゼルシャフト | 腸疾患治療薬 |
US20020177579A1 (en) * | 2000-11-06 | 2002-11-28 | Larry Augsburger | Extended release formulation of water-soluble drugs |
AR036797A1 (es) | 2001-10-15 | 2004-10-06 | Ferring Bv | Un metodo para preparar una composicion farmaceutica que comprende acido 5-aminosalicilico para utilizar en el tratamiento de colitis ulcerosa y enfermedades de crohn |
CN100506234C (zh) | 2001-10-15 | 2009-07-01 | 凡林有限公司 | 用于治疗溃疡性结肠炎和克罗恩病的含有5-氨基水杨酸的药物组合物的制备方法 |
US7025205B2 (en) * | 2002-06-26 | 2006-04-11 | Aventis Pharma Limited | Method and packaging for pressurized containers |
ATE536930T1 (de) | 2002-11-26 | 2011-12-15 | Univ Gent | Verfahren und vorrichtung zur feuchtgranulierung von pulver |
EP1615619A2 (en) | 2003-04-23 | 2006-01-18 | Ferring B.V. | Sachet for a pharmaceutical composition |
EP1547601A1 (en) | 2003-12-23 | 2005-06-29 | Ferring B.V. | Coating method |
JPWO2008102671A1 (ja) * | 2007-02-22 | 2010-05-27 | 味の素株式会社 | 4−ヒドロキシイソロイシンの精製方法 |
EP2340812A1 (en) | 2009-12-18 | 2011-07-06 | Ferring International Center S.A. | Granules for pharmaceutical preparations, methods and apparatus for their production |
-
2004
- 2004-04-22 EP EP04728807A patent/EP1615619A2/en not_active Withdrawn
- 2004-04-22 CA CA002520197A patent/CA2520197A1/en not_active Abandoned
- 2004-04-22 US US10/553,630 patent/US20070042143A1/en not_active Abandoned
- 2004-04-22 WO PCT/EP2004/004280 patent/WO2004093883A2/en active Application Filing
- 2004-04-22 JP JP2006505232A patent/JP2007523664A/ja active Pending
- 2004-04-23 MX MXPA05011308A patent/MXPA05011308A/es active IP Right Grant
- 2004-04-23 US US10/553,629 patent/US8858992B2/en active Active
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- 2004-04-23 EP EP14163036.8A patent/EP2756844A1/en not_active Withdrawn
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- 2004-04-23 CN CN2004800107906A patent/CN1777430B/zh not_active Expired - Lifetime
- 2004-04-23 SI SI200432177T patent/SI1615648T1/sl unknown
-
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- 2005-09-19 IL IL170978A patent/IL170978A/en active IP Right Grant
- 2005-11-23 NO NO20055534A patent/NO335375B1/no unknown
-
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- 2006-04-26 HK HK06104975.5A patent/HK1083312A1/zh not_active IP Right Cessation
-
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- 2009-12-08 JP JP2009278169A patent/JP2010090146A/ja active Pending
-
2010
- 2010-02-26 JP JP2010041157A patent/JP2010179109A/ja not_active Withdrawn
-
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- 2014-08-04 CY CY20141100596T patent/CY1115560T1/el unknown
- 2014-09-11 US US14/483,695 patent/US9402815B2/en not_active Expired - Lifetime
- 2014-12-09 HK HK14112393.2A patent/HK1198917A1/zh unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1207672A (zh) * | 1995-12-21 | 1999-02-10 | 药物实验室费林公司 | 含有5-asa的控释口服药物组合物及其治疗肠道疾病的方法 |
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