CN101626757A - 具有高比例活性剂的快速溶解/崩解的膜剂 - Google Patents
具有高比例活性剂的快速溶解/崩解的膜剂 Download PDFInfo
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- CN101626757A CN101626757A CN200880007219A CN200880007219A CN101626757A CN 101626757 A CN101626757 A CN 101626757A CN 200880007219 A CN200880007219 A CN 200880007219A CN 200880007219 A CN200880007219 A CN 200880007219A CN 101626757 A CN101626757 A CN 101626757A
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- cellulose
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Classifications
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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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- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
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- A—HUMAN NECESSITIES
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- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A—HUMAN NECESSITIES
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Abstract
本发明提供了一种具有高比例(即,至少约40%)活性剂的快速溶解或快速崩解的膜剂及其相关制备方法。在一个实施方式中,所述活性剂是一种药物且所述膜剂包含约10%至约40%的支链淀粉作为主要或唯一水溶性聚合物。
Description
技术领域
本发明一般涉及膜剂,具体涉及具有高比例(即,至少约40%)活性成分的快速溶解或快速崩解的膜剂以及其相关制备方法。
发明背景
各种可溶性膜剂可用于递送药物、营养补充物(例如,维生素和矿物质)和美容剂(例如,牙齿漂白剂、口气清新剂等)之类的活性剂。通常,这种膜剂适合经口给予并且能在口腔内快速溶解或崩解。其他膜剂适合局部给予。
已知膜剂的缺点是,可引入膜剂的活性成分的剂量相对较低。为获得所需柔性、强度、完整性以及操作简便性,成膜聚合物通常占膜剂干重的大部分,而其他成分(例如,增塑剂、调味剂、着色剂等)也占膜剂干重的相当部分。这使得活性剂只占膜剂干重的很小部分。因此,给予高剂量活性剂可能需要使用大到无法接受的膜或者以标准大小的膜给予多次较少活性剂剂量。
已知膜剂的另一个缺点是,许多活性剂高剂量时与常规成膜聚合物不相容。一些情况下其部分原因在于上述缺点,即需要相对高比例的成膜聚合物来制造具有所需完整性、强度和柔性的膜剂。而在另一些情况下,高剂量活性剂与成膜聚合物的不相容性可能是由于实际的化学不相容性。由于这些缺点,膜剂还不适合给予一些活性剂,尤其是需要相对高剂量活性剂的时候。
例如,Zerbe等的美国专利号6,709,671描述了一种口服给予的水溶性膜剂,其包含水溶性聚合物、表面活性剂和活性剂,其中所述聚合物占膜剂干重的20-75%,而活性剂占0.01-20%。这种膜剂不适合给予高剂量(例如,50mg)的活性成分,因为即便活性成分占膜剂干重的20%,含有50mg活性成分的膜剂也需要重250mg。这种膜剂将非常大且不适合口服给予或者定期或不连续地局部给予。
Awamura等的美国专利号6,906,043的权利要求中描述了一种快速溶解的含有药物、聚合物和糖类的膜剂,其中药物占制品重量的0.01-50%,聚合物占20-90%。然而,在所提供的膜剂的所有实例中,药物(尼伐地平、吲哚美辛或氢溴酸非诺特罗)从不超过膜剂干重的20%,而使用的聚合物通常占膜剂干重的至少58%,且通常超过其重量的75%。
Manegold等的美国专利申请公布号20050186257描述了一种制造可溶性膜剂的方法,该膜剂包含至少约18%的水溶性小于约1g/4mL的活性成分(例如,咖啡因)。然而,在所提供的实施例中,活性成分均不超过膜剂干重的约20%。
故而需要一种适合口服或局部给予的包含高比例活性剂的快速溶解或快速崩解的膜剂,从而该膜剂可提供相对高剂量的活性剂。
发明概述
本发明提供了一种具有高比例(即,至少约40%)活性剂的快速溶解或快速崩解的膜剂及其相关制备方法。在一个实施方式中,所述活性剂是药物且所述膜剂包含约10%至约40%的支链淀粉作为主要或唯一水溶性聚合物。
本发明的第一个方面提供了一种快速溶解或快速崩解的膜剂,其包含:占膜剂重量至少约40%的活性剂;占膜剂重量约10%至约40%的至少一种水溶性聚合物,其中所述活性剂在室温时是水溶性差的固体。
本发明的第二个方面提供了一种快速溶解或快速崩解的膜剂,其包含:占膜剂重量至少约40%的活性剂;和作为唯一或主要水溶性聚合物的占膜剂重量约10%至约40%的支链淀粉,其中所述活性剂在室温时是水溶性差的固体。
本发明的第三个方面提供了一种制备包含高剂量活性剂的快速溶解或快速崩解的膜剂的方法,所述方法包括以下步骤:将占膜剂干重约10%至约40%的至少一种水溶性聚合物溶于一定量的水或一定量的水中;在所得溶液中加入占膜剂干重的至少约40%、任选约50%,或任选约60%的至少一种活性剂;将所得悬浮液浇铸在支持基板上;和干燥浇铸的悬浮液以形成膜剂。
本发明的上述方面能解决上述问题和熟练技术人员可发现的未讨论的其他问题。
发明详述
本发明的组合物可包含、构成为、或实质构成为上述本发明的必需元素和限制以及本文所述的任何额外或任选成分、组分或限制。
除非另有说明,所有的百分比、份数和比例基于本发明膜剂组合物的总干重。除非另有说明,这种重量与所列成分有关时皆基于组合物的干重。
术语“安全有效”在文中表示化合物或组合物(如局部或全身性活性物质)的量足以显著诱导积极益处,例如,牙齿美白、抗微生物和/或镇痛益处,还包括本文所披露的益处,但该量足够低从而可避免严重的副作用,即可提供熟练技术人员能够判断范围内的合理的益处风险比。
如上所述,本发明提供了一种具有高比例(即,占膜剂干重的至少约40%,或者任选至少约50%,或者任选至少60%,或者任选至少70%)活性成分的快速溶解或快速崩解的膜剂,从而使得所述活性成分保持安全有效。
任选地,本发明的膜剂是薄膜剂。文中,术语“薄”表示膜厚度为约25μm至约250μm,任选为约40μm至约200μm,或者任选为约80μm至约180μm。
文中,术语“活性物质”、“活性剂”和“活性成分”可互换使用,表示要递送的物质,该物质能够赋予所需作用或效果。这种物质包括,但不限于:药物、药剂、药品、治疗剂、诊断剂、美容剂、营养补充物以及它们的混合物。更具体地说,不局限于本发明的范围,这种物质包括疼痛缓解剂、咳嗽和感冒成分、抗炎药、抗生素、镇静药、刺激物、抗组胺药、抗过敏药、利尿剂、祛痰药、激素、抗精神病药、麻醉剂以及它们的混合物。
术语“活性物质”、“活性剂”和“活性成分”包括活性物质的未修饰形式或分离的加工形式(如包胶形式或颗粒形式)。包胶形式和/或颗粒形式通常用来在膜剂制备之前提供特殊递送特性。所述特殊递送特性可包括,但不限于:掩味、缓释或靶向释放(例如在肠道后部靶向释放)特性或这些特性的组合。
文中,术语“掩味”表示以可觉察的程度降低可能存在的不良味道。
合适的掩味剂包括,但不限于:碳酸氢钠;离子交换树脂,如通过引用全文纳入的Bess等的US 7,067,116中所述的那些;能够形成包含化合物的环糊精,如通过引用全文纳入的Nelson等的US 6,942,848中所述的那些;吸附物质,如通过引用全文纳入的Mozda的US 4,753,800和Caldwell等的US5,622,980中描述的硅酸盐;以及它们的混合物。有用的掩味剂还描述于Julian等的US 4,851,226;Gowan等的US 5,405,617;和Paradissis的US 4,7864,375(以及Stoyle等的US 3,037,911;和Koff的US 3,080,292、3,080,293和3,279,994),所有列出的专利通过引用全文纳入本文。
文中,术语″缓释″、″靶向释放″和″控释″指递送口服活性物质的递送***或制剂的特征为,例如,活性成分被用来控制口服制剂中活性成分的释放速率和/或释放部位的涂层完全或部分覆盖或包裹。
可用在pH约2-3的胃部酸性条件下不可渗透或基本不可渗透但在十二指肠和小肠的更加中性的环境(即,pH大于约5)下可溶的材料涂布活性物质来实现活性物质在小肠的靶向释放。这种控释能防止活性成分由于接触胃部的高酸性环境而降解并维持活性成分的治疗血液水平并随时间持续或稳定释放活性物质一消除了与不够精细的药物***将其活性成分快速释放入消化***有关的峰谷状态。
可通过任何一种缓慢溶出技术实现活性物质通过十二指肠和小肠时的缓释或控释。这些技术包括,但不限于:将活性物质在各种厚度的涂层中胶囊化或微囊化,每种涂层有不同的溶解模式;将活性物质在十二指肠和小肠的中性环境下缓慢溶解的基材中胶囊化;以及使活性物质与粘附于小肠壁的生物粘附剂粘合以提供缓释或靶向释放。这种控释***描述于,例如,Harris的US6,124,477;Fassihi等的US 5,783,212;Newton等的US 5,415,878;Martin等的US 5,225,212;Paradissis等的US 5,133,974;Uemura等的US 4,695,467;Jain等的US 4,610,870;Lowey的US 4,259,314;DeNeale等的US 4,309,404;DeNeale等的US 4,248,857;和Weiler的US 4,140,255,所有专利通过引用全文纳入本文。
诸如流化床造粒、热熔挤出、浸渍、旋转盘和乳液胶凝等各种包衣或包胶技术的详细描述可在Carlo等的US 7,048,948;Becker等的US 2006094097;Sparks等的US 4,675,140;Dannelly的US 4,123,206;Arens等的US 3,423,489和Virgalitto等的US 20050089548中找到,所有这些专利通过引用全文纳入本文。
可用于本文的包衣材料的例子包括,但不限于:聚甲基丙烯酸酯、乙基纤维素、羟丙基甲基纤维素、醋酸-邻苯二甲酸纤维素、邻苯二甲酸羟丙基甲基纤维素、聚醋酸乙烯邻苯二甲酸酯、羧甲基乙基纤维素、甲基丙烯酸和甲基丙烯酸甲酯的共聚物如L12、5或L100(罗姆药厂(RohmPharma))、水基分散体如(FMC公司(FMC Corporation)),L100-55(罗姆药厂)和Coating CE 5142(BASF),以及含有这些的水溶性增塑剂如(辉瑞公司(Pfizer))。有用的Eudrgit化合物更加详细的讨论可在通过引用全文纳入本文的Georgiades等的US 2005196358中找到。
可用于制备包衣活性物质的各种材料、设备和方法的更加详细的信息可在以下文献中找到:Lieberman等编写的《Pharmaceutical Dosage Forms:Tablets》(药物剂型:片剂)(纽约,MD公司(Marcel Dekker,Inc.),1989),Ansel等,《Pharmaceutical Dosage Forms and Drug Delivery Systems》(药物剂型和药物递送***),第6版(Media,Pa.:Williams & Wilkins,1995)以及通过引用全文纳入本文的Talton的美国专利7,063,748。
文中,术语“快速溶解”和“快速崩解”分别表示能够在约1分钟内、任选在约30秒内或者任选约20秒内在个体口腔内、在个体皮肤的湿润表面、或在水性液体中溶解或崩解,但在非水性环境中几乎不溶解和不崩解。文中,“个体”应包括任何动物,包括人。
文中,“水溶性差”应表示室温下在水中的溶解度小于约0.5g/mL。
文中,“室温”应表示从约20℃至约25℃的环境温度。
文中,“干燥”应表示水分含量小于约15重量%,更优选介于约3%至约12重量%,再优选介于约5%至约10重量%。
已经吃惊地发现可制备含有高比例(即,占膜剂干重的至少约40%,任选至少约45%,或者任选至少约50%,或者任选至少约60%)活性剂的快速溶解或快速崩解的薄膜剂。在某些实施方式中,所述活性剂在室温下为水溶性差的固体。任选地,活性剂的含量可以为约40%至约90%,任选约45%至约85%,任选约50%至约80重量%。
合适的水溶性差的固体活性物质的例子可在Dhabhar的美国专利5,484,606;Dennis等的美国专利6,638,537和Sunshine等的美国专利4,522,828中找到,各专利通过引用全文纳入本文。
本发明所述膜剂尤其适用于给予需要以高剂量提供其所需效果的活性剂。例如,几乎不溶于水的布洛芬要求剂量至少约50mg才有效。因此,为通过重约100mg的常规口服膜剂给药则膜剂必需包含约50%的布洛芬。
其他活性剂可能需要甚至更高剂量才有效。例如,仅轻微溶于水的对乙酰氨基酚要求剂量约80mg才有效。因此,100mg的膜剂必须在单个剂量中包含约80%的对乙酰氨基酚才有效。
不局限于理论,水溶性聚合物可为膜剂提供充足的柔性、强度和完整性从而使得膜剂可口服或局部给予。还包含占膜剂干重为约10%至约40%,任选为约10%至约30%,任选为约12%至约18%,或者任选15%的水溶性聚合物。特别优选的水溶性聚合物是支链淀粉。其他合适的可用于实践本发明的水溶性聚合物包括羟丙基甲基纤维素、羟乙基纤维素、羟丙基纤维素、甲基纤维素、聚乙烯吡咯烷酮、羧甲基纤维素、聚乙烯醇、藻酸钠、聚乙二醇、聚环氧乙烷、黄蓍胶、瓜耳胶、金合欢胶、***胶、聚丙烯酸、甲基丙烯酸甲酯共聚物、羧乙烯聚合物、直链淀粉、高直链淀粉淀粉、羟丙基化高直链淀粉淀粉、糊精、果胶、几丁质、脱乙酰壳多糖、果聚糖、爱生兰(elsinan)、胶原、明胶、玉米醇溶蛋白、谷蛋白、大豆蛋白分离物、乳清蛋白分离物、酪蛋白、以及它们的混合物。
本发明所述的膜剂可包含其他成分,如着色剂和调味剂,这是本领域技术人员了解的。还可含有脂肪和表面活性剂以将活性成分原位乳化。然而,本发明所述的膜剂优选不含或基本不含改性淀粉。文中,表述“基本不含改性淀粉”表示改性淀粉在本发明所述膜剂中的浓度为小于膜剂干重约1%,任选小于约0.5%,或任选小于约0.01%,或任选为约0%。尽管改性淀粉一般被用作成膜剂,但这种情况下通常需要大量增塑剂以便为膜剂提供足够的柔性。通常,含有改性淀粉的膜剂包含多达50%的增塑剂以提供这种柔性。假设本发明所述膜剂的活性剂比例高,增塑剂的这种高含量将无法接受。改性淀粉包括,例如,玉米淀粉、改性木薯淀粉、酸水解玉米淀粉、酸水解马铃薯淀粉、酶解玉米淀粉、酶解马铃薯淀粉、次氯酸盐氧化淀粉、酸稀化淀粉、乙基化淀粉、交联淀粉、羟丙基化木薯淀粉、羟丙基化玉米淀粉、预胶凝改性淀粉,以及它们的组合。
增塑剂或塑化剂通常占膜剂干重的约0%至约20%,优选占干重的约2%至约10%。软化剂可包括含有(例如)山梨醇和其他多元醇、甘油、聚乙二醇、丙二醇、氢化淀粉水解产物、玉米糖浆、其他类似材料或其组合的增塑剂。
上面讨论的这些额外成分以及在本文中有用的其他成分进一步详细披露于Zerby等的US 5,948,430;Leung等的US 6,596,298;Dzija等的US 6,656,493;和Barkalow等的US 20060024425,各专利通过引用全文纳入本文。
本发明所述的膜剂可通过任何方法制备,但浇铸是优选方法。例如,一旦制得含有活性剂和水溶性聚合物的悬浮液(将在下文中更加详细地描述),可使用刀、棒、或挤出模涂布法将悬浮液浇铸到诸如聚酯等基材上,并干燥以形成膜剂。优选地,本发明所述的膜剂被干燥至水分含量小于约15重量%,更优选至约3%至约12%,再优选至约5%至约10%。
一旦浇铸并干燥,本发明所述膜剂的厚度优选为约25微米至约250微米,但膜剂的厚度将部分取决于所需的给药方式。此外,本发明所述的膜剂可由单层或多个层构成。在本发明的多层膜剂中,所有层的总厚度优选为约25微米至约250微米。这种制备方法进一步详细描述于之前通过引用纳入本文作为的专利US 6,596,298中。
现在将参考以下实施例更加充分地描述本发明,提供这些实施例仅出于阐述或解释目的而并非要限制本发明。
实施例1-50%活性物质,35%聚合物
实施例1的膜剂的制备如下。将乙酰舒泛钾和三氯蔗糖加入水中并溶解。任选将纯水预加热至40-50℃。此外,可任选使用含有水和乙醇的溶剂。优选的用于口服膜剂的醇是乙醇。将聚合物混合物成分预混合、加入并混合。然后加入调味剂/着色剂混合物成分,之后加入布洛芬。然后将所得悬浮液浇铸到合适的基材上并干燥制成独立的薄膜剂。然后切割该膜剂以得到含50mg布洛芬的单次膜剂(或条带)剂量。
实施例2-77%活性物质,16%聚合物
采用类似于实施例1的方法制备含80mg对乙酰氨基酚的快速溶解薄膜剂。在制备该实施例的制剂时,对乙酰氨基酚的形式可以是非微粉化对乙酰氨基酚、微粉化对乙酰氨基酚或预成型的掩味对乙酰氨基酚颗粒(例如,用乙基纤维素、甲基纤维素、聚甲基丙烯酸酯、聚乙烯醇、果胶、聚乙烯吡咯烷酮、各种脂肪和蜡、长链脂肪酸如硬脂酸、或者它们的混合物涂布的对乙酰氨基酚)。
实施例3-81%活性物质,16%聚合物
采用类似于实施例1的方法制备含80mg对乙酰氨基酚的快速溶解薄膜剂。
实施例4-52%活性物质,36%聚合物
采用类似于实施例1的方法制备含50mg阿替洛尔(一种β阻断剂)的快速溶解薄膜剂。
实施例5-52%活性物质,36%聚合物
采用类似于实施例1的方法制备含45mg富马酸亚铁(矿物质补充物)的快速溶解薄膜剂。
实施例6-81%活性物质,14%聚合物
采用类似于实施例1的方法制备含100mg愈创甘油醚(一种祛痰剂)的快速溶解薄膜剂。
实施例7-77%活性物质,16%聚合物
采用类似于实施例1的方法制备含约80mg对乙酰氨基酚(一种镇痛药)的快速溶解薄膜剂。在该实施例中,对乙酰氨基酚用甘油和聚山梨酯80预乳化于少量水中,然后再加入最终的混合物。预混合的目的是形成一种乳化剂-活性物质联合体以得到更好的分散和味道特性。术语“乳化剂-活性物质联合体(emulsifier-active association)”在文中表示活性物质被乳化剂分子部分或完全包被或围绕。
实施例8-50.8%活性物质,11.7%聚合物:
组分 | 毫克/膜 | %w/w干重 | %w/w湿重 | |
纯水 | 0.0000 | 0.0000 | 51.0190 | |
乙酰舒泛钾 | 0.1515 | 0.1539 | 0.0754 | |
三氯蔗糖 | 2.7787 | 2.8227 | 1.3826 | |
掩味布洛芬负载量为62.5% | 80.0000 | 81.2662 | 39.8050 | |
混合胶 | ||||
黄原胶 | 0.0758 | 0.0770 | 0.0377 | |
豆角胶 | 0.0758 | 0.0770 | 0.0377 | |
角叉菜胶 | 0.3873 | 0.3934 | 0.1927 | |
支链淀粉 | 8.4211 | 8.5543 | 4.1900 | |
聚乙烯吡咯烷酮 | 2.5263 | 2.5663 | 1.2570 | |
混合调味剂 | ||||
甘油 | 0.4211 | 0.4277 | 0.2095 | |
聚山梨酯80 | 0.3218 | 0.3269 | 0.1601 | |
Atmos 300 | 0.3218 | 0.3269 | 0.1601 | |
Neobee 1053 | 0.6451 | 0.6554 | 0.3210 | |
薄荷调味剂 | 2.2737 | 2.3097 | 1.1313 | |
绿#3 | 0.0420 | 0.0427 | 0.0209 | |
总计 | 98.441904 | 100.0000 | 100.0000 |
采用类似于实施例1的方法制备含80mg掩味布洛芬(一种镇痛药)的快速溶解薄膜剂。用于该实施例的颗粒在制造膜剂之前已经通过旋转盘方法用脂肪和蜡涂布以进行掩味。涂布过程(也可参考实施例2)可以是任何常规类型的造粒或包胶方法。例子包括,但不限于,流化床造粒、热熔挤出、旋转盘包胶、相分离型包胶。
实施例9-49.8%,36%聚合物
采用类似于实施例1的方法制备含50mg布洛芬和10mg缓释的盐酸苯肾上腺素(5mg盐酸苯肾上腺素)的快速溶解薄膜剂。通过实施例8所述的流化床法,用乙基纤维素和羟丙基甲基纤维素的组合涂布苯肾上腺素以提供缓释特性。如上所述,该膜剂可含有活性成分的组合(如本实施例所述,例如布洛芬和缓释苯肾上腺素颗粒的组合),从而使所得膜剂具有缓释(或控释)特性。
实施例10-49.8%活性物质,36%聚合物.
采用类似于实施例1的方法制备含50mg布洛芬和10mg缓释的盐酸苯肾上腺素(5mg盐酸苯肾上腺素)的快速溶解薄膜剂。通过实施例8所述的流化床法,以流传床造粒机用乙基纤维素和羟丙基甲基纤维素的组合涂布苯肾上腺素以提供控释特性。如该实施例和实施例9所述,尽管所述膜剂本身是一种快速溶解膜剂,但递送的活性物质的药理学作用可持续或延迟和/或靶向胃肠道的特定部分。可采用典型的流化床造粒机用聚甲基丙烯酸酯涂布颗粒并使涂层在pH高于5时在消化道的后部崩解。
Claims (7)
1.一种快速溶解或快速崩解的膜剂,其包含:
活性剂,其占膜剂重量的至少40%,优选40-90%,更优选50-80%,最优选50-70%;和
至少一种水溶性聚合物,优选支链淀粉,其占膜剂重量的10-40%,优选10-30%,更优选12-18%,
其中所述活性剂在室温时是水溶性差的固体。
2.如权利要求1所述的膜剂,其特征在于,所述活性剂包括至少一种选自下组的化学物质:药物、美容剂、维生素、矿物质或其混合物。
3.如上述权利要求中任一项所述的膜剂,其特征在于,所述至少一种水溶性聚合物选自下组:支链淀粉、羟丙基甲基纤维素、羟乙基纤维素、羟丙基纤维素、甲基纤维素、聚乙烯吡咯烷酮、羧甲基纤维素、聚乙烯醇、藻酸钠、聚乙二醇、聚环氧乙烷、黄蓍胶、瓜耳胶、金合欢胶、***胶、聚丙烯酸、甲基丙烯酸甲酯共聚物、羧乙烯聚合物、直链淀粉、高直链淀粉淀粉、羟丙基化高直链淀粉淀粉、糊精、果胶、几丁质、脱乙酰壳多糖、果聚糖、爱生兰、胶原、明胶、玉米醇溶蛋白、谷蛋白、大豆蛋白分离物、乳清蛋白分离物、酪蛋白以及它们的混合物。
4.如上述权利要求中任一项所述的膜剂,其特征在于,经调整所述膜剂在1分钟内在口腔内充分溶解或分离。
5.一种制备包含高剂量活性剂的快速溶解或快速崩解的膜剂的方法,所述方法包括以下步骤:
将占膜剂干重的10%-40%,优选10%-30%,更优选15%的含量的至少一种水溶性聚合物溶于一定量的水或一定量的水和乙醇中;
将占膜剂干重至少40%,优选40%-90%,更优选50%-80%,最优选50%-70%的含量的至少一种活性剂加入所得溶液中;
将所得悬浮液流延在支持基板上;和
干燥流延的悬浮液以形成膜剂。
6.如权利要求5所述的方法,其特征在于,所述至少一种水溶性聚合物选自下组:支链淀粉、羟丙基甲基纤维素、羟乙基纤维素、羟丙基纤维素、甲基纤维素、聚乙烯吡咯烷酮、羧甲基纤维素、聚乙烯醇、藻酸钠、聚乙二醇、聚环氧乙烷、黄蓍胶、瓜耳胶、金合欢胶、***胶、聚丙烯酸、甲基丙烯酸甲酯共聚物、羧乙烯聚合物、直链淀粉、高直链淀粉淀粉、羟丙基化高直链淀粉淀粉、糊精、果胶、几丁质、脱乙酰壳多糖、果聚糖、爱生兰、胶原、明胶、玉米醇溶蛋白、谷蛋白、大豆蛋白分离物、乳清蛋白分离物、酪蛋白以及它们的混合物。
7.如上述权利要求中任一项所述的方法,其特征在于,所述至少一种活性剂选自下组:药物、药剂、药品、治疗剂、诊断剂、美容剂、营养补充物和它们的混合物。
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US20030211136A1 (en) * | 1998-09-25 | 2003-11-13 | Neema Kulkarni | Fast dissolving orally consumable films containing a sweetener |
US20030206942A1 (en) * | 1998-09-25 | 2003-11-06 | Neema Kulkarni | Fast dissolving orally consumable films containing an antitussive and a mucosa coating agent |
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US7067116B1 (en) * | 2000-03-23 | 2006-06-27 | Warner-Lambert Company Llc | Fast dissolving orally consumable solid film containing a taste masking agent and pharmaceutically active agent at weight ratio of 1:3 to 3:1 |
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WO2004019885A2 (en) * | 2002-08-29 | 2004-03-11 | Linguagen Corp. | Fast dissolving film delivery of nucleotides that inhibit the unpleasant taste of bitter tasting medications |
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US20070059346A1 (en) * | 2003-07-01 | 2007-03-15 | Todd Maibach | Film comprising therapeutic agents |
US20050170138A1 (en) * | 2004-01-20 | 2005-08-04 | Berry Craig J. | Laminated thin film with increased dosage loading and improved physical film properties and method for manufacture |
US20050186257A1 (en) * | 2004-02-20 | 2005-08-25 | Todd Manegold | Dissolvable film and method of manufacture |
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MX2007007885A (es) * | 2004-12-23 | 2007-10-04 | Johnson & Johnson | Composiciones farmaceuticas oralmente desintegrables con agentes de indicacion sensorial. |
-
2007
- 2007-03-05 US US11/714,007 patent/US20080220029A1/en not_active Abandoned
-
2008
- 2008-02-26 CN CN200880007219A patent/CN101626757A/zh active Pending
- 2008-02-26 EP EP08726047.7A patent/EP2131824B1/en not_active Not-in-force
- 2008-02-26 AU AU2008223583A patent/AU2008223583B2/en not_active Ceased
- 2008-02-26 BR BRPI0808475-0A patent/BRPI0808475A2/pt not_active Application Discontinuation
- 2008-02-26 CA CA002679370A patent/CA2679370A1/en not_active Abandoned
- 2008-02-26 MX MX2009009463A patent/MX2009009463A/es not_active Application Discontinuation
- 2008-02-26 EP EP11195471A patent/EP2444076A1/en not_active Withdrawn
- 2008-02-26 RU RU2009136580/15A patent/RU2492854C2/ru not_active IP Right Cessation
- 2008-02-26 KR KR1020097018321A patent/KR20090128402A/ko not_active Application Discontinuation
- 2008-02-26 WO PCT/US2008/002462 patent/WO2008108940A1/en active Application Filing
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2010
- 2010-06-15 HK HK10105997.0A patent/HK1139854A1/zh not_active IP Right Cessation
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102552195A (zh) * | 2010-12-10 | 2012-07-11 | 日东电工株式会社 | 片状制剂和片状制剂的制造方法 |
CN102552219A (zh) * | 2010-12-10 | 2012-07-11 | 日东电工株式会社 | 片状制剂和片状制剂的制造方法 |
CN106999445A (zh) * | 2014-11-04 | 2017-08-01 | 阿库科特公司 | ***口腔膜剂 |
US11083734B2 (en) | 2014-11-04 | 2021-08-10 | Acucort Ab | Dexamethasone oral film |
CN106606779A (zh) * | 2015-10-19 | 2017-05-03 | 浙江安吉山争医药包装科技有限公司 | 一种可食性膜片及其制备方法 |
CN110505871A (zh) * | 2017-03-13 | 2019-11-26 | 纳米及先进材料研发院有限公司 | 用于药物吸收的高负载快速崩解膜 |
CN110505871B (zh) * | 2017-03-13 | 2023-08-15 | 纳米及先进材料研发院有限公司 | 用于药物吸收的高负载快速崩解膜 |
Also Published As
Publication number | Publication date |
---|---|
EP2444076A1 (en) | 2012-04-25 |
HK1139854A1 (zh) | 2010-09-30 |
KR20090128402A (ko) | 2009-12-15 |
RU2009136580A (ru) | 2011-04-10 |
AU2008223583B2 (en) | 2013-08-15 |
US20080220029A1 (en) | 2008-09-11 |
BRPI0808475A2 (pt) | 2014-07-15 |
MX2009009463A (es) | 2009-09-15 |
EP2131824A1 (en) | 2009-12-16 |
EP2131824B1 (en) | 2014-09-24 |
RU2492854C2 (ru) | 2013-09-20 |
AU2008223583A1 (en) | 2008-09-12 |
CA2679370A1 (en) | 2008-09-12 |
WO2008108940A1 (en) | 2008-09-12 |
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