CN101686931B - 用于制备可咀嚼片剂和锭剂的药物配制剂 - Google Patents
用于制备可咀嚼片剂和锭剂的药物配制剂 Download PDFInfo
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- CN101686931B CN101686931B CN2008800189904A CN200880018990A CN101686931B CN 101686931 B CN101686931 B CN 101686931B CN 2008800189904 A CN2008800189904 A CN 2008800189904A CN 200880018990 A CN200880018990 A CN 200880018990A CN 101686931 B CN101686931 B CN 101686931B
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- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
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- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Landscapes
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Abstract
本发明涉及用于制备可咀嚼片剂和锭剂的药物配制剂,所述配制剂包含基于糖或糖醇、崩解剂和水不溶性聚合物的附聚体以及提高粘度/形成凝胶的聚合物。本发明进一步涉及相应的可咀嚼片剂和锭剂。
Description
本发明涉及用于制备可咀嚼和可吮吸片剂的药物配制剂,所述配制剂包含基于糖或糖醇、崩解剂和水不溶性聚合物的附聚体以及提高粘度/形成凝胶的聚合物,和相应的可咀嚼和可吮吸片剂。
可咀嚼和可吮吸片剂对药物的口服给药而言变得日益重要。这种片剂必须易于咀嚼、具有愉悦的味道和必须不留下沙砾感。此外,它们应易于制备,其中直接制片相对于湿造粒具有明显优势,且应具有高机械强度从而使它们经受得住包装程序、运输以及从包装中压出而不损坏。
至今描述的产品和方法不能或仅非常不足地满足这些要求。
WO 2003/051338描述了包含甘露醇和山梨醇的可直接制片且易于压制的赋形剂配制剂。首先,通过将甘露醇和山梨醇溶于水中并随后喷雾干燥(常规喷雾干燥和SBD法)而制备赋形剂预混物。也可将甘露醇加入此共加工的混合物中。额外包含崩解剂、助流剂、颜料和活性成分的片剂据说在口腔中在60秒内崩解。
US 2002/0071864A1描述了在口腔中在60秒内崩解且主要由喷雾干燥的甘露醇、粗粒交联聚乙烯吡咯烷酮和有限选择的活性成分的物理混合物配制的片剂。这些片剂的硬度为约40N并产生不愉悦的沙砾口感。
根据US 6,696,085B2,将类型C的甲基丙烯酸共聚物用作崩解剂。类型C的甲基丙烯酸共聚物为抗胃液且在酸性pH范围内不溶但在如存在于口腔中的7的pH范围内可溶于水的聚合物。除低硬度(<20N)外,所述片剂具有高脆性(>7%)和15重量%的高粗粒崩解剂含量。它们因此具有低机械强度,并由于高粗粒崩解剂含量而产生不愉悦的沙砾口感。
EP 0839526A2描述了由活性成分、赤藓醇、晶体纤维素和崩解剂组成的药物剂型。此外,加入甘露醇并将交联的聚乙烯吡咯烷酮用作崩解剂,从而形成物理混合物。据说所述片剂在口腔中在60秒内分解。
申请WO 2006/029787描述了在口中在60秒内崩解且由活性成分、水 溶性聚乙烯醇/聚乙二醇共聚物、糖/糖醇(甘露醇)和崩解剂组成的片剂。
本发明的目的是提供具有良好味道,留下愉悦口感,同时易于咀嚼和吮吸然而还非常机械稳定的可咀嚼和可吮吸片剂。
因此发现用于制备可咀嚼和可吮吸片剂的药物制剂,所述制剂包含:
A)由如下组分组成的附聚体:
a1)60-97重量%至少一种糖或糖醇或其混合物,
a2)1-25重量%崩解剂,
a3)1-15重量%水不溶性聚合物,
a4)0-15重量%水溶性聚合物,和
a5)0-15重量%其它药物常规赋形剂,
其中组分a1)-a5)的总和为100重量%,
和
B)提高粘度或形成凝胶的聚合物。
所述制剂可包含20-99重量%,优选40-90重量%附聚体A)和0.1-25重量%,优选1-15重量%组分B)。
如果需要,也可加入0-5重量%润滑剂作为组分C),0.1-50重量%药物活性成分作为组分D)和0-25重量%其它药物赋形剂作为组分E)。此时A)、B)以及如果存在的C)、D)和E)的量的总和为100%。
此外,已发现相应的可咀嚼和可吮吸片剂。
赋形剂内容物A)具有如下特定组成:
所述药物制剂包含60-97重量%,优选70-95重量%,特别优选75-93重量%糖、糖醇或其混合物作为组分a1)。适合的糖或糖醇为海藻糖、甘露醇、赤藓醇、异麦芽糖、麦芽糖醇、乳糖醇、木糖醇和山梨醇。糖或糖醇组分优选是细碎的,平均粒度为5-100μm。如果需要,粒度可通过研磨调整。优选的粒度为30-50μm。然而,合理的是也可使用小于30μm的粒度。同样合理的是可使用包含粒度不同的部分的混合物的糖或糖醇,例如30-70重量%平均粒度<30μm的粒度部分和30-70重量%平均粒度为30-50μm的粒度部分的混合物。优选使用甘露醇、赤藓醇或其混合物。
将量为1-25重量%,优选2-15重量%,特别优选3-10重量%的崩解 剂用作组分a2)。崩解剂优选选自交联的聚乙烯吡咯烷酮、交联羧甲基纤维素、羧甲基淀粉钠和L-羟基丙基纤维素。根据本发明,交联羧甲基纤维素指交联羧甲基纤维素的钠和/或钙盐。优选的L-羟基丙基纤维素具有5-16%羟基丙氧基。特别优选交联的聚乙烯吡咯烷酮。这种交联的聚乙烯吡咯烷酮为水不溶性但非成膜性的。交联的聚乙烯吡咯烷酮的平均粒度可为2-60μm,优选小于50μm,特别优选小于30μm。
将量为1-15重量%,优选1-10重量%的水不溶性聚合物用作组分a3)。优选的聚合物为在1-14的pH范围内不溶,即具有在每个pH下为pH独立的水不溶性的那些。然而,在6-14的pH范围中的任何pH下为水不溶性的聚合物也适合。
聚合物应为成膜聚合物。在本上下文中,成膜指聚合物在水分散体中的最低成膜温度为-20至+150℃,优选0-100℃。
适合的聚合物为聚乙酸乙烯酯、乙基纤维素、甲基丙烯酸甲酯/丙烯酸乙酯共聚物、丙烯酸乙酯/甲基丙烯酸甲酯/甲基丙烯酸三甲基铵乙酯三聚物。甲基丙烯酸丁酯/甲基丙烯酸甲酯/甲基丙烯酸二甲基氨基乙酯三聚物。
欧洲药典以聚丙烯酸酯分散体30%、USP以Ammonio甲基丙烯酸酯共聚物和JPE以甲基丙烯酸氨基烷基酯共聚物E更详细地描述了丙烯酸酯/甲基丙烯酸酯共聚物。将聚乙酸乙烯酯用作优选的组分c)。其可以固体含量为10-45重量%的水分散体使用。另外,优选的聚乙酸乙烯酯为分子量为100000-1000000道尔顿,特别优选200000-800000道尔顿的那种。
此外,所述配制剂可包含量为0-15重量%的水溶性聚合物作为组分a4)。适合的水溶性聚合物例如为聚乙烯吡咯烷酮或乙烯基吡咯烷酮/乙酸乙烯酯共聚物、聚乙烯醇/聚乙二醇接枝共聚物、聚乙二醇和乙二醇/丙二醇嵌段共聚物。
如果需要,由所述配制剂得到的片剂的味道和外观可通过加入量为0-15重量%的药物常规赋形剂(组分a5))如酸化剂、缓冲物质、增甜剂、香料、香味增强剂和着色剂而进一步改善。在本文中如下物质特别适合:柠檬酸、酒石酸、抗坏血酸、磷酸二氢钠、环己烷氨基磺酸盐、糖精钠、天冬氨酰苯丙氨酸甲酯、薄荷醇、薄荷香料、水果香料、香草香料、谷氨酸盐、核黄素、β-胡罗卜素、水溶性着色剂和细碎的色淀。
通过加入增稠剂如高分子量多糖,口感可另外通过提高软度和体积感(sensation of volume)而改善。
此外,表面活性剂也可作为组分a5)加入。适合的表面活性剂例如为月桂基硫酸钠、磺基琥珀酸二辛酯、烷氧基化脱水山梨糖醇酯如聚山梨醇酯80、蓖麻油或氢化蓖麻油的多烷氧基化衍生物如RH40、烷氧基化脂肪酸、烷氧基化羟基脂肪酸、烷氧基化脂肪醇、脂肪酸的碱金属盐和卵磷脂。
此外,也可加入细碎的颜料以进一步改善崩解,因为它们增加了内部界面,水因此可更快速地渗入片剂中。这些颜料如铁氧化物、二氧化钛、胶状或沉淀硅石、碳酸钙或磷酸钙当然必须非常细碎,因为否则再次产生粒状味觉。
所述制剂包含提高粘度或形成凝胶的聚合物或其混合物作为组分B)。提高粘度或形成凝胶的聚合物可为:琼脂、藻酸盐如藻酸钠、角叉菜聚糖、瓜耳胶、刺槐豆胶、塔拉胶、芦荟、果胶、黄原胶、结冷胶(gellan)、右旋糖苷、凝胶多糖、支链淀粉、羟基丙基甲基纤维素(HPMC)、羟基丙基纤维素(HPC)、羧甲基纤维素钠、羟基乙基纤维素(HEC)、淀粉、改性淀粉、脱乙酰壳多糖、聚丙烯酸钠、泊洛沙姆和聚乙烯醇。优选的聚合物B为黄原胶、藻酸盐、HPMC和HPC。
通常将本发明制剂与至少一种用于制备片剂的活性成分混合。
原则上可使用所有活性成分作为活性成分。优选使用,特别优选以所述剂量使用以下所述活性成分:
佐米曲普坦2.5mg,利扎曲普坦5mg,盐酸苯海拉明(掩味的)20mg,溴苯那敏5mg,氯苯那敏5mg,伪麻黄碱(掩味的)30mg,对乙酰氨基酚(掩味的)250mg,布洛芬(掩味的)200mg,乙酰水杨酸250mg(掩味的),硫酸莨菪碱0.125mg,米氮平15mg,盐酸司来吉兰1.25mg,昂丹司琼4mg,奥氮平5mg,氯硝西泮1mg,盐酸西替立嗪10mg,地氯雷他定5mg,马来酸依那普利5mg,马来酸多潘立酮10mg,东莨菪碱0.25mg,奥沙西泮15mg,劳拉西泮2.5mg,氯氮平25mg,甲磺酸双氢麦角胺5mg,尼麦角林5mg, 间苯三酚80mg,美托哌丙嗪7.5mg,三唑仑0.5mg,溴替唑仑(protizolam)0.5mg,曲马多50mg,酒石酸唑吡坦5mg,西沙比利5mg,利培酮2mg,阿奇霉素100mg(掩味的),罗红霉素50mg(掩味的),克拉霉素125mg(掩味的),依托红霉素250mg(掩味的),阿扑吗啡20mg,芬太尼0.6mg,两性霉素10mg,铝碳酸镁500mg,镁加铝500mg,镁盐10-500mg,钙盐10-500mg,紫锥菊提取物80mg,氧化铝200mg,氢氧化镁200mg,孟鲁司特钠盐5mg,地喹氯铵0.25mg,西吡氯铵1mg,盐酸丁丙诺啡0.4-8mg,劳拉西泮1-5mg,氟代磷酸二钠50-100mg,盐酸氨溴索20mg,苯佐卡因10mg,氯己定2HCl5mg,氟比洛芬10mg。
也可使用活性成分的混合物。所述剂量表示每种药物剂型相应活性成分的绝对量。最终药物剂型中赋形剂内容物和活性成分内容物的浓度取决于药物剂型的大小。在可咀嚼或可吮吸片剂的情况下,通常的片剂重量为100-2000mg。
也可向活性成分提供常规掩味涂层。用于这种涂层的适合聚合物为:甲基丙烯酸氨基烷基酯共聚物E(Eudragit E或EPO),各种配制剂中的聚乙烯醇(Opadry AMB、Kollicoat Protect),水不溶性聚合物如聚乙酸乙烯酯的组合,聚(甲基)丙烯酸酯(Eudragit NE 30D、NM 30D、RL、RS、RD、Kollicoat EMM 30D),具有水溶性或水溶胀性低或高分子量物质的乙基纤维素(聚维酮、共聚维酮、HPMC、HPC、聚乙二醇、泊洛沙姆、聚乙二醇-聚乙烯醇接枝共聚物、糖、糖醇、有机或无机盐),水溶性成膜剂(聚乙二醇-聚乙烯醇接枝共聚物、HPMC、聚乙烯醇)与脂肪、蜡、脂肪酸和脂肪醇的组合。
附聚体A)可通过在混合机、流化床设备或喷雾塔中附聚而制备。首先将固体原料和造粒液体相互混合,然后将潮湿的混合原料干燥。根据本发明,所用造粒液体为组分a3)水不溶性聚合物的水分散体。
在本发明一个实施方案中,首先将一种或多种活性成分与糖或糖醇、崩解剂以及如果需要组分a4)和a5)一起引入流化床中。
根据其它实施方案,在不存在活性成分下使组分a1)-a5)附聚。
在流化床附聚中,将水不溶性聚合物(组分a3))的水分散体喷雾在糖或 糖醇、崩解剂、如果需要活性成分以及如果需要其它组分d)和e)的流化混合物上,从而导致细颗粒的附聚。入口气温为30-100℃,出口气温为20-70℃。
尤其随着所述附聚可加入如下赋形剂作为其它组分e):着色剂、增甜剂、香料、其它崩解剂、碳酸盐、碳酸氢盐、酸化剂或其它赋形剂。在可使用无机颜料、有机色淀或水溶性着色剂的情况下,使用着色剂例如导致均匀着色的快速崩解片剂。适合着色剂的实例为核黄素、β-胡罗卜素、花色素、胭脂红、靛蓝胭脂红、有机黄S、喹啉黄、靛蓝色淀、亮蓝、晚霞黄。这些其它物质可以固体形式放入流化床初始加料中或溶于或分散于组分a3)的分散体中。如果分散体与这种物质不相容,则后者也可在与组分a3)的分散体附聚之前或之后以溶液或作为悬浮液喷雾。
当在喷雾塔中制备时,优选使用所谓的FSD或SBD技术(FSD:流化喷雾干燥;SBD:喷雾床干燥)。此时,首先将糖或糖醇的水溶液喷雾干燥,并在喷雾塔的较低部分或在连接的流化床中加入崩解剂和喷入水不溶性聚合物的水分散体,从而产生颗粒附聚物。此外,可在糖或糖醇溶液的喷嘴前方再次吹细颗粒,并另外使其附聚。从晶体形式的糖或糖醇开始的程序在喷雾塔、FSD或SBD中也可以。在喷雾塔的顶部加入晶体糖或糖醇或将其加入细原料的再循环料流中。通过喷雾水不溶性聚合物的水分散体,该晶体固体在塔中附聚。
可证明对附聚法有利的是进行多级喷雾加工。开始时,保持低喷雾速率以防止初始加入的产物过湿及其因此的粘附。随着加工时间的增加,可提高喷雾速率,并因此可提高附聚的倾向。也可在加工期间以适当方式调整入口气流速率和/或温度。特别是在干燥相期间,有利的是降低入口气流速率并因此防止附聚体由于高机械应力而磨损。
可将粘合剂溶液或分散体的喷雾液滴的细度(可通过雾化气压调整)、喷嘴几何形状和喷嘴至产物床的距离认为是附聚体大小的其它调整参数。喷雾越细且越均匀,所得附聚体越细且越均匀。喷嘴离产物床越远,附聚行为越差。
此外,附聚也可在混合机中通过在混合下连续聚集而进行。这种在混 合下的连续聚集形式为所谓的“Schugi造粒”。此时,使固体原料和包含水不溶性聚合物的造粒液体在连续操作的垂直设置高速混合机中相互完全混合(还参见M.Bohnet,“Mechanische Verfahrenstechnik”,Wiley VCHVerlag,Weinheim 2004,第198页及随后各页)。
根据具体实施方案,将崩解剂悬浮在水不溶性聚合物的水分散体中。
由此得到的附聚体的平均粒度为100-600μm,优选120-500μm,特别优选140-400μm。水不溶性成膜聚合物用作用于使细糖或糖醇晶体、活性成分颗粒、崩解剂和如果存在其它赋形剂附聚成颗粒的凝结剂。
在本发明其它实施方案中,也可首先使赋形剂内容物A)附聚,然后使A)在其它造粒步骤中与一种或多种活性成分一起附聚。
在该实施方案的变体中,首先将附聚的赋形剂内容物和活性成分引入流化床中,并通过粘合剂溶液造粒。此时粘合剂溶液包含选自组分d)的水溶性聚合物作为粘合剂。其优选为水溶液。粘合剂浓度可为5-40重量%。优选的粘合剂为Fikentscher K值为10-100,特别是K30的水溶性聚乙烯吡咯烷酮,由30-70重量%,优选40-60重量%N-乙烯基吡咯烷酮和30-70重量%,优选40-60重量%乙酸乙烯酯组成的乙烯基吡咯烷酮-乙酸乙烯酯共聚物,聚乙烯醇以及聚乙二醇与聚乙烯醇的接枝共聚物。
在第二个变体中,首先将附聚的赋形剂内容物引入流化床中,并将活性成分内容物加入上述粘合剂溶液中。
在其中水溶性粘合剂(组分a4))必须已优选以0.5-10重量%的量存在于预附聚的赋形剂内容物中的其它变体中,所用造粒液体为无聚合物粘合剂的水。此时可将组分a5)的其它赋形剂加入水中用于造粒。合理的是还可将一种所述糖或糖醇加入水中。
另外,用于其中首先使赋形剂内容物附聚的所有这些实施方案的变体中的设备和工艺参数与上文就使赋形剂内容物和活性成分内容物同时附聚所述相同。
本发明配制剂可有利地用于制备可咀嚼和可吮吸片剂。对片剂的制备而言,可使用常规方法,其中直接制片和辊压特别有利。由于本发明配制剂的特殊性能,通常仅需要活性成分、本发明配制剂和润滑剂。因此,所 述片剂配制剂非常简单,非常易可再生产,且所述方法易于确立。
此外,本发明配制剂具有极好的可流动性和可压制性,这导致机械上非常稳定的片剂。借助本发明药物配制剂制备的片剂的硬度>50N。硬度通常为80N以上,即便是使用难以压制的活性成分。脆性<0.2%。因此在常规片剂加工期间不存在损坏。
因此,本发明配制剂在储存期间非常稳定且保持其吸引人的外观。
实施例
使通过流化床附聚制备的快速崩解赋形剂与活性成分、提高粘度/形成凝胶的聚合物和2.0重量%润滑剂(硬脂酸镁)在Turbula混合机中混合10分钟。然后将这些混合物在装备完全的偏心压机(Korsch XP1)中制片(30个冲程/分钟)。
表1:以重量%表示的配制剂A-D的组成
A | B | C | D | |
甘露醇(d0.5:36μm) | 85.7 | 81.2 | 76.2 | 77.2 |
Kollidon CL-SF | 4.8 | 4.4 | 4.2 | 4.4 |
Kollicoat SR30D(固体) | 4.8 | 4.4 | 4.2 | 4.4 |
藻酸盐 | 2.5 | - | 5.0 | - |
Xanthural 75 | - | 5.0 | - | 10.0 |
咖啡因(细粉) | - | 8.4 | ||
氟比洛芬 | - | 3.0 | 2.0 | |
地喹氯铵 | 0.2 | |||
硬脂酸镁 | 2.0 | 2.0 | 2.0 | 2.0 |
将10mm冲床(双平面,有刻面)用于将混合物A-D制片。将片剂压至300mg的重量和40-50N的硬度。
使用19kN的压力将混合物D的片剂压至1000mg的重量和16mm的直径。
调查片剂的硬度(来自Kraemer的HT-TMB-Cl-12F片剂测试仪)、在pH为7.2的磷酸盐缓冲液中的崩解时间(ZT 74崩解测试仪,Erweka)和在胃液中的释放速率(释放设备,Erweka)。
表2:配制剂A-D的片剂性能
Claims (21)
1.一种用于可咀嚼和可吮吸片剂的药物配制剂,所述配制剂包含:
A)由如下组分组成的附聚赋形剂内容物:
a1)60-97重量%糖或糖醇,
a2)1-25重量%选自交联聚维酮、交联羧甲基纤维素、羧甲基淀粉钠和L-羟基丙基纤维素的崩解剂,
a3)1-15重量%水不溶性成膜聚合物,
a4)0-15重量%水溶性聚合物,和
a5)0-15重量%其它药物常规赋形剂,
其中组分a1)-a5)的总和为100重量%,
B)0.1-25重量%至少一种提高粘度或形成凝胶的聚合物,
其中所述配制剂包含一种或多种选自琼脂、藻酸盐、角叉菜聚糖、瓜耳胶、刺槐豆胶、塔拉胶、芦荟、果胶、黄原胶、结冷胶、右旋糖苷、凝胶多糖、羟基丙基甲基纤维素(HPMC)、羟基丙基纤维素(HPC)、羧甲基纤维素钠、羟基乙基纤维素(HEC)、淀粉、改性淀粉、脱乙酰壳多糖、聚丙烯酸钠、泊洛沙姆和聚乙烯醇的聚合物作为组分B。
2.根据权利要求1的配制剂,其中所述配制剂包含一种或多种选自藻酸钠和支链淀粉的聚合物作为组分B。
3.根据权利要求1的配制剂,所述配制剂包含:
A)由如下组分组成的附聚赋形剂内容物:
a1)60-97重量%糖或糖醇,
a2)1-25重量%选自交联聚维酮、交联羧甲基纤维素、羧甲基淀粉钠和L-羟基丙基纤维素的崩解剂,
a3)1-15重量%水不溶性成膜聚合物,
a4)0-15重量%水溶性聚合物,和
a5)0-15重量%其它药物常规赋形剂,
其中组分a1)-a5)的总和为100重量%,
B)至少一种提高粘度或形成凝胶的聚合物,
C)基于所有组分的总量为0-10重量%的润滑剂,和
D)至少一种药物活性成分。
4.根据权利要求2的配制剂,所述配制剂包含:
A)由如下组分组成的附聚赋形剂内容物:
a1)60-97重量%糖或糖醇,
a2)1-25重量%选自交联聚维酮、交联羧甲基纤维素、羧甲基淀粉钠和L-羟基丙基纤维素的崩解剂,
a3)1-15重量%水不溶性成膜聚合物,
a4)0-15重量%水溶性聚合物,和
a5)0-15重量%其它药物常规赋形剂,
其中组分a1)-a5)的总和为100重量%,
B)至少一种提高粘度或形成凝胶的聚合物,
C)基于所有组分的总量为0-10重量%的润滑剂,和
D)至少一种药物活性成分。
5.根据权利要求1-4中任一项的配制剂,所述配制剂除组分A)-D)外还包含其它药物赋形剂E)。
6.根据权利要求1-4中任一项的配制剂,所述配制剂包含崩解剂作为组分E。
7.根据权利要求1-4中任一项的配制剂,所述配制剂包含量为0.2-5%的润滑剂D。
8.根据权利要求1-4中任一项的配制剂,所述配制剂包含硬脂酸镁或硬脂酸作为润滑剂D。
9.根据权利要求1-4中任一项的配制剂,所述配制剂包含甘露醇或赤藓醇或其混合物作为糖醇。
10.根据权利要求1-4中任一项的配制剂,所述配制剂包含交联羧甲基纤维素钠或钙盐。
11.根据权利要求1-4中任一项的配制剂,所述配制剂包含具有5-16%羟基丙氧基的L-羟基丙基纤维素。
12.根据权利要求1-4中任一项的配制剂,所述配制剂包含交联聚维酮作为崩解剂。
13.根据权利要求1-4中任一项的配制剂,所述配制剂包含聚乙酸乙烯酯作为水不溶性成膜聚合物。
14.根据权利要求1或2的配制剂,其中以水分散体的形式使用水不溶性成膜聚合物聚乙酸乙烯酯。
15.根据权利要求1-4中任一项的配制剂,其中将聚乙烯吡咯烷酮用作水溶性聚合物。
16.根据权利要求1-4中任一项的配制剂,其中将酸化剂、增甜剂、香料、香味增强剂、增稠剂、表面活性剂和细碎的颜料用作其它药物常规赋形剂。
17.根据权利要求1-4中任一项的配制剂,其中将着色剂用作其它药物常规赋形剂。
18.根据权利要求1-4中任一项的配制剂,所述配制剂包含由如下组分组成的附聚体A):
a1)70-95重量%糖或糖醇,
a2)2-15重量%崩解剂,
a3)1-10重量%水不溶性成膜聚合物,
a4)0-2重量%水溶性聚乙烯吡咯烷酮,和
a5)0-15重量%其它药物常规赋形剂。
19.根据权利要求1-4中任一项的配制剂,所述配制剂包含由如下组分组成的附聚体A):
a1)75-95重量%甘露醇或赤藓醇或其混合物,
a2)3-10重量%崩解剂,
a3)1-10重量%聚乙酸乙烯酯,
a4)0-2重量%水溶性聚乙烯吡咯烷酮,和
a5)0-15重量%其它药物常规赋形剂。
20.根据权利要求1-4中任一项的配制剂,所述配制剂包含藻酸盐或黄原胶或羟基丙基甲基纤维素作为组分B)。
21.一种使用根据权利要求1-20中任一项的药物配制剂得到的可咀嚼或可吮吸片剂。
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CN110833561A (zh) * | 2019-12-24 | 2020-02-25 | 正大制药(青岛)有限公司 | 一种奥美拉唑复方咀嚼片 |
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EP2164461A1 (de) | 2010-03-24 |
EP2164461B1 (de) | 2013-01-23 |
CN101686931A (zh) | 2010-03-31 |
US20100184785A1 (en) | 2010-07-22 |
WO2008148734A1 (de) | 2008-12-11 |
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