CN112822998A - 新型剂型 - Google Patents
新型剂型 Download PDFInfo
- Publication number
- CN112822998A CN112822998A CN201980065485.3A CN201980065485A CN112822998A CN 112822998 A CN112822998 A CN 112822998A CN 201980065485 A CN201980065485 A CN 201980065485A CN 112822998 A CN112822998 A CN 112822998A
- Authority
- CN
- China
- Prior art keywords
- dosage form
- soft chewable
- chewable dosage
- famotidine
- active pharmaceutical
- 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
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- 239000002552 dosage form Substances 0.000 title claims abstract description 54
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- 238000000034 method Methods 0.000 claims abstract description 8
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- 201000010099 disease Diseases 0.000 claims abstract description 4
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- 229960001596 famotidine Drugs 0.000 claims description 64
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 claims description 64
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- -1 isomers Chemical class 0.000 claims description 16
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Abstract
本发明涉及软咀嚼剂型以及使用软咀嚼剂型治疗患有胃肠道疾病或障碍的受试者的方法，所述软咀嚼剂型包含包封在脂质材料中的第一活性药物成分，所述脂质材料包埋在软咀嚼剂型中，并且其中所述软咀嚼剂型包含至少第二活性药物成分。
Description
技术领域
本发明涉及软咀嚼剂型以及使用此类软咀嚼剂型治疗患有胃肠道疾病或障碍的受试者的方法，所述软咀嚼剂型包含包封在脂质材料/基质中的第一活性药物成分，所述脂质材料/基质包埋在软咀嚼剂型中，并且其中所述软咀嚼剂型包含至少第二活性药物成分。
背景技术
组胺H2受体拮抗剂，例如西米替丁、雷尼替丁、尼西替丁、罗西替丁和法莫替丁，通过直接作用于胃壁的胃腺内的酸分泌胃壁细胞而减少酸分泌。
虽然组胺H2受体拮抗剂在治疗许多胃障碍尤其是消化道溃疡和胃溃疡方面显著有效，但存在某些对治疗没有反应的患者群体。此外，给药和起效之间的时间推移限制了组胺H2受体拮抗剂在治疗急性、自限性胃障碍方面的潜在有益效果。
组胺H2受体拮抗剂在急性、自限性胃障碍诸如胃酸过多症的自我药疗中具有潜在的有益效果。然而，它们缓慢的起效不可能满足消费者快速减轻症状的需求。
已探索了组胺H2受体拮抗剂和其它药物活性物质(包括抗酸剂)的共同施用。与抗酸剂共同施用的基本原理是，抗酸剂通过中和而快速缓解胃酸过多的症状，而组胺H2受体拮抗剂通过抑制酸从胃壁细胞分泌而独立起作用。
如今使用的抗酸剂由多种无机盐制成，如碳酸钙、碳酸氢钠、镁盐和铝盐。氢氧化镁和氢氧化铝是最有效的镁盐和铝盐，并且通常组合使用。此外，也可采用氧化铝、氧化镁、碳酸镁、磷酸铝、水化铝酸镁、三硅酸镁和蔗糖硫酸铝(硫糖铝)。
然而，法莫替丁的共同给药常常非常困难，因为法莫替丁对湿度极其敏感，并且可在此类条件下立即开始降解。
发明内容
本发明涉及新改善软咀嚼剂型的开发，所述新改善软咀嚼剂型包含包封在脂质材料/基质中的第一活性药物成分，所述脂质材料/基质包埋在软咀嚼剂型中，并且其中所述软咀嚼剂型包含至少第二活性药物成分。一个示例包括包封在脂质材料中并包埋在包含至少一种抗酸剂的软咀嚼剂型中的法莫替丁。
本发明使得能够首次以软咀嚼剂型递送法莫替丁/抗酸剂组合。该形式确保法莫替丁的稳定性，并且在抚慰和包衣疼痛的食道组织方面提供更好的感官体验，从而给予消费者更快的行动补救。
软咀嚼形式固有地具有高水含量。如果将原始法莫替丁共混到基质中，则高含量的水可有助于降解(法莫替丁的水解)。在本发明的情况下，脂质插入件/材料防止水进入法莫替丁颗粒中并防止进一步相互作用和水解。
最后，本发明涉及在应用中使用如上文和下文所定义的软咀嚼片剂治疗患有胃肠道疾病或障碍(诸如烧心)的受试者的方法。
附图说明
图1示出了具有不同MCT量的样品的力测量值。
具体实施方式
定义
在本专利申请和发明的上下文中，以下定义适用：
术语“软咀嚼”旨在表示在咀嚼时保持其完整性和质地，在咀嚼时不分解成离散的固体片或颗粒并且旨在被吞咽的剂型。软咀嚼物是可口的、可食用的，并且在质地上类似于糖果的松软或牛轧糖。
术语“％w/w”旨在表示“成分的百分比/按组合物的重量计的总百分比(100％)”。
如本文所用，“剂量”、“剂型”、“剂量单位”或“剂”意指一次施用的包含一种或多种治疗活性剂的药物成分的量。“剂量”、“剂型”、“剂量单位”或“剂”包括同时施用一个或多个单位的药物成分。
术语“胃病或障碍”主要旨在表示在增加的酸分泌的产生，其导致受治疗者的胃灼热和一些恼人的胀气症状，也称为消化不良。消化不良，也称为胃弱，是消化受损的病症。症状可包括上腹部饱胀感、胃灼热、恶心、腹痛或上腹部疼痛。在进食时，人们可能也会比预期更早体验到的饱胀。胃弱是一种常见问题，并且经常由胃食管反流性疾病(GERD)或胃炎引起。
软咀嚼剂型
在一个实施方案中，本发明涉及软咀嚼剂型，该新改善软咀嚼剂型包含包封在脂质材料/基质中的第一活性药物成分，所述脂质材料/基质包埋在软咀嚼剂型中，并且其中所述软咀嚼剂型包含至少第二活性药物成分。
在一个示例中，包封的活性药物成分包含至少一种组胺H2受体拮抗剂，诸如西咪替丁、雷尼替丁、尼扎替丁、罗沙替丁和法莫替丁、它们的药学上可接受的盐、异构体和异构体的盐。
在另一个实施方案中，H2受体拮抗剂为法莫替丁，并且第二活性药物成分为至少一种抗酸剂。
脂质包封的法莫替丁的粒度为约100微米至约5000微米，诸如约200微米至约2000微米。
法莫替丁作为固体小珠包埋并存在于剂型中的脂质基质内。可将小珠施加在软咀嚼剂型的表面上或插入(作为插入件)软咀嚼剂型中。为了制备该小珠，将法莫替丁悬浮或分散在脂质基料中并作为小珠沉积。其可作为小珠沉积并固化，该小珠随后被施加到软咀嚼物；或以液体形式施加并沉积在原位固化的软咀嚼物上。该固化可通过室温下的附加冷却步骤或该室温(25℃)下的温度冷却器来促进。法莫替丁作为分散的固体或固溶体存在于脂质小珠中。
本发明的脂质小珠的直径为约2毫米至约15毫米，或约3毫米至约8毫米。脂质小珠的重量可以在约20mg至约150mg、或约30mg至约80mg的范围内。
在另一个实施方案中，法莫替丁作为多个颗粒存在，其中此类颗粒包衣有至少一种脂质材料或聚合物。如本文所用，多个颗粒由包含法莫替丁的至少两个颗粒单元限定。
所述至少一种抗酸剂选自碳酸钙、碳酸氢钠、氢氧化镁、氧化铝、氢氧化铝、氧化镁、碳酸镁、磷酸铝、水合镁和三硅酸镁。
包封/包衣活性药物成分的脂质材料选自鲸蜡硬脂醇、甘油二山嵛酸酯、棕榈酰硬脂酸甘油酯、单/双甘油酯或氢化植物油或植物油。脂质材料的其它示例包括但不限于脂肪酸酯，诸如蔗糖脂肪酸酯、甘油一酯、甘油二酯和甘油三酯、单硬脂酸甘油酯、三硬脂酸甘油酯、三月桂酸甘油酯、肉豆蔻酸甘油酯、Glyco Wax-932、月桂酰聚乙二醇-32甘油酯和硬脂酰聚乙二醇-32甘油酯；磷脂，诸如包括磷脂酰胆碱、磷脂酰丝氨酸、磷脂酰肌醇和磷脂酸的磷脂；蜡，诸如卡洛巴蜡、鲸蜡、蜂蜡、小烛树蜡、虫胶蜡、微晶蜡和石蜡；以及脂肪，诸如氢化植物油，诸如例如可可油、氢化棕榈仁油、氢化棉籽油、氢化向日葵油和氢化大豆油；以及游离脂肪酸和它们的盐。这些脂质也适于用作脂质小珠或材料内的主要脂质。
在某些实施方案中，可将乳化剂或第二脂质添加到主要脂质中，以便软化或改变脂质小珠或材料的质地。第二脂质也可充当增塑剂。乳化剂包括但不限于聚乙烯脱水山梨糖醇单油酸酯(聚山梨酸酯60和80)、甘油酯、甘油基酯、单油酸甘油酯和单油酸酯。适于用作增塑剂的第二脂质包括但不限于中链甘油三酯(MCT)。乳化剂或第二脂质(增塑剂)可以按脂质小珠或材料的重量计约5重量％至约50重量％、或约5重量％至约30重量％的量存在于脂质小珠或材料中。
如果法莫替丁为活性药物成分，则其可为颗粒、小珠或压片的形式。
除了法莫替丁和一种或多种抗酸剂之外，软咀嚼剂型还可包含二甲基硅油作为活性药物成分。二甲基硅油可存在于包含抗酸剂的软咀嚼基料中，或存在于包含法莫替丁的脂质小珠或丸剂中。
软咀嚼片剂还可包含一种或多种成分，所述一种或多种成分选自由脂肪、蛋白质、着色剂、风味剂、甜味剂、增稠剂、乳化剂、抗氧化剂、防腐剂、润滑剂、助流剂、胶凝剂和崩解剂组成的列表。
风味剂的示例是胡椒薄荷、留兰香、桉树、甘草、香草、焦糖、混合浆果、混合水果、黑加仑、蓝莓、樱桃和柠檬。
如果需要的话，活性药物成分中的一种或多种是掩味的。掩味技术是本领域中技术人员熟知的。
赋形剂的示例包括脂肪、蛋白质、填充剂、助流剂、润滑剂、甜味剂、风味剂、着色剂、填充剂、粘结剂/胶凝剂以及它们的混合物。
合适的润滑剂包括长链脂肪酸以及它们的盐(例如硬脂酸镁和硬脂酸)、滑石、甘油酯、蜡以及它们的混合物。
合适的助流剂包括胶态二氧化硅。
甜味剂的示例包括合成糖或天然糖；人造甜味剂，诸如糖精、糖精钠、三氯蔗糖、天冬甜素、丁磺氨、非洲甜果素、甘草素、三氯蔗糖、环磺酸盐、二氢查尔酮、阿力甜、奇异果素和应乐果甜蛋白；糖醇，诸如山梨醇、甘露糖醇、甘油、乳糖醇、麦芽糖醇和木糖醇；从甘蔗和糖用甜菜提取的糖(蔗糖)、右旋糖(也称为葡萄糖)、果糖(也称为左旋糖)和乳糖(也称为奶糖)；异麦芽酮糖醇、甜菊糖、以及它们的混合物。
着色剂的示例包括色淀和被批准用作食品添加剂的染料。
可使用的填充剂的示例包括玉米糖浆、蔗糖、淀粉、脂肪、蛋白质和明胶。可用于软咀嚼基质中的附加材料包括玉米糖浆固体、蔗糖、淀粉、脂肪、蛋白质和/或明胶。
在一个实施方案中，剂型是包衣的。剂型可用基于糖或糖醇的包衣或膜包衣包覆。用于基于糖或糖醇的包衣的材料的示例包括但不限于蔗糖、右旋糖或木糖醇。用于膜包衣的聚合物的示例包括但不限于羟丙甲纤维素和聚乙烯醇以及聚乙烯醇：聚乙二醇共聚物以及它们的混合物。
法莫替丁的量可为约2mg至约30mg，并且一种或多种抗酸剂的量为约200mg至约3000mg。脂质小珠部分内法莫替丁的量可为按脂质小珠部分的重量计约5重量％至约40重量％或约10重量％至约30重量％。
诸如法莫替丁的组胺H2受体拮抗剂可以约2mg至约30mg的量存在，诸如4mg至20mg或8mg至12mg或2mg、3mg、4mg、5mg、6mg、7mg、8mg、9mg、10mg、11mg、12mg、13mg、14mg、15mg、16mg、17mg、18mg、19mg、20mg、21mg、22mg、23mg、24mg、25mg、26mg、27mg、28mg、29mg或30mg。
抗酸剂可以约200mg至约3000mg的量存在。如果利用两种不同的抗酸剂，则它们可以是相同的量或不同的量，这取决于具体的组合。示例为具有约400mg至约1000mg量的碳酸钙和约50mg至约300mg量诸如约100mg至约200mg的氢氧化镁的剂型，所述碳酸钙为诸如600mg、700mg、800mg、900mg或1000mg，所述氢氧化镁为诸如100mg、110mg、120mg、130mg、140mg、150mg、160mg、165mg、170mg、180mg、190mg或200mg。如果使用氧化铝或氢氧化铝，则其可以约200mg至约600mg的量使用，诸如300mg、400mg、500mg或600mg。
在另一方面，本发明涉及软咀嚼片剂，其中包封的活性药物成分为洛哌丁胺，并且其它活性药物成分为至少一种二甲基硅油。
还希望含有法莫替丁的脂质小珠和周围含有抗酸剂的软咀嚼基质在咀嚼时具有类似的质地。质地可通过分析随时间推移的力来确定。在本发明的这个方面，在脂质小珠和软咀嚼基料之间，随时间推移的力的总面积差小于10000g/秒。
在本发明的另一方面，法莫替丁不随时间推移而降解。在该方面，当在40℃和75％相对湿度下储存3个月时，剂型中总法莫替丁杂质的量小于1.5％，并且当在40℃和75％相对湿度下储存3个月时，任何单一杂质少于1.0％。
以下实施例旨在以任何方式、形状或形式明确或隐含地说明而非限制本发明。
实施例1：在可熔可食用基质中制备法莫替丁小珠(插入件)
如下制备法莫替丁热熔融溶液和一体化软咀嚼物：
1.根据表1中的基础比率配方制备大约30g批料。
2.将可熔可食用基质中的材料在大约70℃的不锈钢容器中熔融。将法莫替丁分散在熔融材料中并连续混合以保持均匀分布。
3.使用移液管传送测量量的熔融混合物以形成小珠，所述小珠随后在冷却时固化。
4.基础配方内不同材料的变化示于表2中。
表1：基础法莫替丁小珠可食用基质配方
*亲脂热塑性材料，所述亲脂热塑性材料在一些示例中还含有增塑剂以软化所述材料。
表2：含有法莫替丁的小珠的初始成分
| 配方1 | ||
| 成分 | mg/片 | ％重量/重量 |
| SP Crodacol CS50<sup>1</sup>(鲸蜡硬脂醇) | 56.67 | 85.00 |
| 法莫替丁 | 10.00 | 15.00 |
| 66.67 | 100.00 | |
| 配方2 | ||
| 成分 | mg/片 | ％重量/重量 |
| Compritol 888ATO<sup>2</sup>(二山嵛酸甘油酯) | 56.67 | 85.00 |
| 法莫替丁 | 10.00 | 15.00 |
| 66.67 | 100.00 | |
| 配方3 | ||
| 成分 | mg/片 | ％重量/重量 |
| Geleol<sup>3</sup>(单甘油酯/双甘油酯，NF) | 56.67 | 85.00 |
| 法莫替丁 | 10.00 | 15.00 |
| 66.67 | 100.00 | |
| 配方4 | ||
| 成分 | mg/片 | ％重量/重量 |
| 甾醇(氢化棉籽油，NF) | 56.67 | 85.00 |
| 法莫替丁 | 10.00 | 15.00 |
| 66.67 | 100.00 | |
| 配方5 | ||
| 成分 | mg/片 | ％重量/重量 |
| SP Crodacol CS50<sup>1</sup>(鲸蜡硬脂醇) | 43.34 | 65.00 |
| Gelucire<sup>4</sup> 50/13(硬脂酰聚氧乙烯-32甘油酯) | 13.33 | 20.00 |
| 法莫替丁 | 10.00 | 15.00 |
| 66.67 | 100.00 | |
| 配方6 | ||
| 成分 | mg/片 | ％重量/重量 |
| Compritol 888ATO(二山嵛酸甘油酯) | 43.34 | 65.00 |
| Gelucire 50/13(硬脂酰聚氧乙烯-32甘油酯) | 13.33 | 20.00 |
| 法莫替丁 | 10.00 | 15.00 |
| 66.67 | 100.00 |
1：可从Croda Corporation商购获得
2：可从Gattefosse Corporation商购获得
3：可从Gattefosse Corporation商购获得
4：可从Gattefosse Corporation商购获得
实施例2：稳定性评估
将来自实施例1(配方1至6)的小珠在琥珀色玻璃广口瓶中暴露于不同的条件以确定法莫替丁的稳定性。相对于以400μg/mL制备的标准法莫替丁储备溶液，使用具有以下参数的HPLC分析法莫替丁和法莫替丁杂质测定：
柱：高级色谱技术(ACE)C8,3μm
(150mm×4.6mm内径)，ACE-112-1546
移动相：磷酸钠缓冲液：ACN的梯度方法(98:2v/v至30:70，经过26分钟)
流速：1.0mL/min
注入体积：15mL
278nm下的UV检测器
样品制备包括以下步骤：
对于含有二山嵛酸甘油酯(Compritol)的样品：添加50mL氯仿并涡旋直至溶解。用氯仿稀释至体积并充分混合。
对于含有鲸蜡硬脂醇(Crodacol)的样品：添加50mL甲醇并使用机械摇动器混合直至溶解。用甲醇稀释至体积并充分混合。
部分A：在琥珀色玻璃广口瓶中的储存：
表3汇总了稳定性研究结果。
表3.稳定性研究结果–储存在琥珀色玻璃广口瓶中的小珠
a：FAM-A1：法莫替丁杂质A1
b：FAM-A3：法莫替丁杂质A3
c：FAM-A6：法莫替丁杂质A6
d：FAM UDP：法莫替丁未指定的降解产物
RT-室温
RH–相对湿度
部分B：开放式盘碟储存
选择样品1和2中的配方用于开放式盘碟稳定性评估。将样品置于开放式盘碟中并置于相应的稳定环境中。
表4汇总了在40℃/75％RH(相对湿度)下进行3个月的开放式盘碟研究期间法莫替丁在小珠中的稳定性结果。在3个月后观察到法莫替丁的降解最小。
表4.稳定性研究结果–开放式盘碟稳定性
实施例3：具有各种含量的中链甘油三酯(MCT)和力测量值的样品
为了软化小珠使得质地类似于软咀嚼物，将具有相关联的力测量值的不同含量的MCT添加到如表5中所示的Crodacol和Compritol中。
分析力测量值，以将表5中的小珠与商业
软咀嚼物进行比较，以更紧密地匹配软咀嚼成分和小珠之间的感官质地。使用具有以下测试参数的质地特性分析仪测量硬度：
材料厚度–大约20mm的固体块
探针–可替换的针探针
测力传感器–5Kg
测试特性–以0.2mm/秒刺入2mm
结果：含有30％MCT油的共混物具有最低硬度值(图中未包括)。对于稳定性研究，选择15％MCT油以使油从小珠到软咀嚼基质中的浸出最小化。
表5：具有各种含量的MCT的样品
图1示出了具有不同MCT量的样品的力测量值。
实施例4：法莫替丁小珠在软咀嚼物中的稳定性
当与法莫替丁小珠组合时，将
软咀嚼物用于基础稳定性研究。稳定性结果示于表7中。
与软咀嚼物组合使用的小珠成分在表6中示出。
表6：成分与软咀嚼物组合
*添加MCT油以软化小珠基质
用于稳定性研究的样品制备：将5gm
软咀嚼物切成6片。对于每个测试条件，称出大约总计200mg的具有法莫替丁的小珠。将一个或两个小珠插入每个经切割的咀嚼片中，并且对于每个条件执行两次。
样品储存：将样品置于琥珀色广口瓶中并在初始和40C/75％RH下稳定放置2周、4周、2个月和3个月时间点。
以下成分显示在商业
Softchew的包装件上。
活性成分
在每种咀嚼物中：碳酸钙USP(1330mg)、氢氧化镁USP(235mg)。
非活性成分
玉米淀粉、玉米糖浆、玉米糖浆固体、甘油、氢化椰子油、卵磷脂、天然和人造风味剂、红40色淀、蔗糖、水。
其他信息
每种咀嚼物含有：钙535mg、镁100mg。在干燥位置储存在68℉至77℉之间(20℃至25℃)。
表7：与软咀嚼组合的法莫替丁小珠的稳定性结果
实施例5：包衣的颗粒和剂型
部分A：法莫替丁制粒
表8：用于法莫替丁颗粒的制粒成分(1.5kg批料)
| ％(w/w) | 1.5kg批料的克数 | |
| 乳糖一水合物，可植入NF | 81.00 | 1215 |
| 法莫替丁USP | 13.00 | 195 |
| 羟丙甲纤维素E5优质USP | 6.00 | 90 |
| 纯化水USP | xxx | 810 |
1.乳糖一水合物和法莫替丁通过40目筛网。
2.将总水的三分之二加热至70-80℃。将羟丙甲纤维素缓慢地添加到水中，同时使用高剪切混合器混合。添加剩余的水。将溶液冷却并使其脱气。
3.在Huttlin Diskjet单元中通过以50cc/分钟喷射来自步骤2的制粒流体进行制粒。制粒完成后，将颗粒干燥并排放以用于热熔融包衣。
4.制粒后，在热熔融包衣之前使材料通过18目。
部分B：热熔融包衣
对于热熔融包衣，在Huttlin Diskjet单元中将棕榈酰硬脂酸甘油酯(可以Precirol ATO从Gattefosse corporation商购获得)加热至约60℃的温度，并且喷射在来自部分A的法莫替丁颗粒上。以30％的增重率包衣颗粒。
部分C：掺入包衣的颗粒的软咀嚼制剂
使用部分A中的法莫替丁包衣的颗粒制备以下剂型。
表9
1.共混方法：将42玉米糖浆加热至90℃并使用实验室顶置式混合器与甘油共混。
2.在步骤1中将糖果、碳酸钙、氢氧化镁、玉米糖浆固体添加到液体共混物中。
3.在单独的容器中将椰子油加热至40-45℃并与卵磷脂共混。
4.将来自部分A的包衣法莫替丁颗粒与椰子油和卵磷脂的混合物共混，并且然后添加到来自步骤2的共混物中。最后添加调味剂和着色剂。在添加包衣的法莫替丁期间，最终混合物的温度为大约40℃。
5.将软咀嚼物共混物混合直至均匀。
6.将共混物冷却并固化，并且手动切割成5g的片。
Claims (19)
1.一种软咀嚼剂型，所述软咀嚼剂型包含包封在脂质材料/基质中的第一活性药物成分，其中所述脂质包封的活性药物成分包埋在所述软咀嚼剂型中，并且其中所述软咀嚼剂型包含至少第二活性药物成分。
2.根据权利要求1所述的软咀嚼剂型，其中所述脂质包封的活性药物成分包含至少一种组胺H2受体拮抗剂。
3.根据权利要求2所述的软咀嚼剂型，其中所述H2受体拮抗剂选自西米替丁、雷尼替丁、尼扎替丁、罗西替丁和法莫替丁、它们的药学上可接受的盐、异构体和异构体的盐。
4.根据权利要求3所述的软咀嚼剂型，其中所述H2受体拮抗剂为法莫替丁，并且所述第二活性药物成分为至少一种抗酸剂。
5.根据权利要求4所述的软咀嚼剂型，其中所述脂质包封的法莫替丁的粒度为约100微米至约5000微米，诸如约200微米至约2000微米。
6.根据权利要求4所述的软咀嚼剂型，其中所述至少一种抗酸剂选自碳酸钙、碳酸氢钠、氢氧化镁、氢氧化铝、氧化铝、氧化镁、碳酸镁、磷酸铝、水化铝酸镁和三硅酸镁。
7.根据权利要求1至6所述的软咀嚼剂型，其中所述脂质材料选自鲸蜡硬脂醇、二山嵛酸甘油酯、单甘油酯/双甘油酯、氢化植物油或植物油。
8.根据权利要求1至7中任一项所述的软咀嚼剂型，其中法莫替丁为颗粒、小珠或压片、丸剂或迷你片。
9.根据权利要求1至8中任一项所述的软咀嚼剂型，其中脂质材料被增塑以匹配所述软咀嚼基质的质地。
10.根据权利要求9所述的软咀嚼剂型，其中所述增塑剂为按所述脂质材料的重量计在约5％至约50％范围内的中链甘油三酯(MCT)油。
11.根据权利要求1至10所述的软咀嚼剂型，其中所述至少一种抗酸剂选自碳酸钙、碳酸氢钠、氢氧化镁、氢氧化铝、氧化铝、氧化镁、碳酸镁、磷酸铝、水化铝酸镁和三硅酸镁。
12.根据权利要求1至11所述的软咀嚼剂型，其中所述第三活性药物成分包含二甲基硅油。
13.根据前述权利要求中任一项所述的软咀嚼剂型，其中所述软咀嚼剂型还包含一种或多种成分，所述一种或多种成分选自由着色剂、风味剂、甜味剂、增稠剂、乳化剂、抗氧化剂、防腐剂、胶凝剂和崩解剂组成的列表。
14.根据权利要求13所述的软咀嚼剂型，其中所述风味剂选自胡椒薄荷、留兰香、桉树、甘草、香草、焦糖、混合浆果、混合水果、黑加仑、蓝莓、樱桃和柠檬。
15.根据前述权利要求中任一项所述的软咀嚼剂型，其中所述一种或多种活性药物成分是掩味的。
16.根据前述权利要求中任一项所述的软咀嚼剂型，其中法莫替丁以约2mg至约30mg的量存在。
17.根据前述权利要求中任一项所述的软咀嚼剂型，其中所述抗酸剂以约200mg至约3000mg的量存在。
18.通过使用根据权利要求1至17中任一项所述的软咀嚼剂型来治疗患有胃肠道疾病或障碍的受试者的方法。
19.通过使用根据权利要求1-15中任一项所述的软咀嚼剂型来治疗患有烧心的受试者的方法。
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| CN113143876A (zh) * | 2020-12-30 | 2021-07-23 | 河南合智医药科技有限公司 | 一种稳定的复方法莫替丁咀嚼片及其制备方法 |
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| EA202191063A1 (ru) | 2021-07-12 |
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