CN113750052B - 一种乙酰半胱氨酸颗粒及其制备方法 - Google Patents
一种乙酰半胱氨酸颗粒及其制备方法 Download PDFInfo
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- CN113750052B CN113750052B CN202111218132.8A CN202111218132A CN113750052B CN 113750052 B CN113750052 B CN 113750052B CN 202111218132 A CN202111218132 A CN 202111218132A CN 113750052 B CN113750052 B CN 113750052B
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- acetylcysteine
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- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 title claims abstract description 143
- 229960004308 acetylcysteine Drugs 0.000 title claims abstract description 132
- 239000008187 granular material Substances 0.000 title claims description 33
- 238000002360 preparation method Methods 0.000 title claims description 17
- 239000006187 pill Substances 0.000 claims abstract description 37
- 239000003814 drug Substances 0.000 claims abstract description 32
- 239000002245 particle Substances 0.000 claims abstract description 31
- 239000011159 matrix material Substances 0.000 claims abstract description 29
- 229940079593 drug Drugs 0.000 claims abstract description 20
- 238000002955 isolation Methods 0.000 claims abstract description 19
- 239000002994 raw material Substances 0.000 claims abstract description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 26
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- 108010011485 Aspartame Proteins 0.000 claims description 18
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- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 18
- 235000010357 aspartame Nutrition 0.000 claims description 18
- 229960003438 aspartame Drugs 0.000 claims description 18
- 235000005976 Citrus sinensis Nutrition 0.000 claims description 17
- 240000002319 Citrus sinensis Species 0.000 claims description 17
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 16
- 239000000600 sorbitol Substances 0.000 claims description 16
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 14
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 14
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 14
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 14
- 239000004474 valine Substances 0.000 claims description 14
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 13
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 claims description 13
- 238000000227 grinding Methods 0.000 claims description 12
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 11
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 11
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 11
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 11
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 11
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 11
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- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
- 235000004279 alanine Nutrition 0.000 claims description 6
- 229920002307 Dextran Polymers 0.000 claims description 5
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 claims description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
- 229930182817 methionine Natural products 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 4
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-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 claims description 2
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 108010024636 Glutathione Proteins 0.000 description 3
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
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- 230000008569 process Effects 0.000 description 2
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- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
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Abstract
本发明属于药物制剂领域,提供一种乙酰半胱氨酸颗粒,包括含有乙酰半胱氨酸的药丸以及药学上可接受的辅料,其中所述含有乙酰半胱氨酸的药丸包括以下重量份组分:10份乙酰半胱氨酸原料药、20‑50份防潮基质、7‑13份隔离基质。本发明通过采用防潮基质和隔离基质双重基质对乙酰半胱氨酸原料药进行处理,不仪能够避免原料药吸潮,还能降低原料药的酸臭味,并且颗粒细腻,不易结块。
Description
技术领域
本发明属于药物制剂领域,具体涉及一种乙酰半胱氨酸颗粒及其制备方法。
背景技术
乙酰半胱氨酸(N-acetylcysteine,NAC)分子式是C5H9NO3S,是L-半胱氨酸的乙酰化合物,在20世纪60年代开始应用,成为临床祛痰药。NAC为还原型谷胱甘肽(GSH)的前体,属于体内氧自由基清除剂,具有提高机体内谷胱甘肽含量和抗生物氧化的作用。其还常用于解救对乙酰氨基酚引起的肝毒性反应,这可能与维持或恢复谷胱甘肽水平有关。另外,NAC也可能通过改善血液动力力学和氧输送能力,扩张微循环发挥肝脏保护作用。近些年,随着对NAC进一步的研究,发现其对多种呼吸道疾病,如慢性阻塞性肺疾病、支气管哮喘、急性呼吸窘迫综合症、肺间质纤维化等均具有很好的治疗和预防作用。NAC具有多种药理作用,且新作用仍不断被探索发现。NAC的临床应用领域也不断拓宽,在药物及重金属中毒、动脉粥样硬化、肿瘤、艾滋病、老年性痴呆、帕金森病以及吸烟损害等过程中都起到预防、治疗作用。但是NAC有类似蒜的臭气,味酸,患者服用时常因其酸臭味而引发不适感,并且NAC还具有较强的引湿性,长时间放置易吸潮而影响药效。
专利CN 102144978 B公开了一种乙酰半胱氨酸颗粒及其制备工艺,主要由乙酰半胱氨酸、丙烯酸树脂、甘露醇、阿司帕坦、甜橙香精组成。采用丙烯酸树脂对乙酰半胱氨酸进行包衣后,再与甘露醇干颗粒、阿司帕坦、甜橙香精进行混合,制备的乙酰半胱氨酸颗粒可明显提高对湿的稳定性,同时显著改善口味。但是该专利中采用丙烯酸树脂对乙酰半胱氨酸粉末进行包衣,容易出现膜衣发粘的问题,与其他辅料粘接后形成较大颗粒,影响颗粒剂的分散均匀性。另外,该专利中仅仅通过甘露醇、阿司帕坦、甜橙香精等辅料调节乙酰半胱氨酸的酸臭味,调节味道方面仍有待提高。
发明内容
本发明旨在提供一种乙酰半胱氨酸颗粒及其制备方法,克服了现有技术中改善乙酰半胱氨酸引湿性和酸臭味效果欠佳的问题。
本发明提供一种乙酰半胱氨酸颗粒,该颗粒包括含有乙酰半胱氨酸的药丸以及药学上可接受的辅料,其中所述含有乙酰半胱氨酸的药丸包括以下重量份组分:10份乙酰半胱氨酸原料药、20-50份防潮基质、7-13份隔离基质。
进一步地,所述乙酰半胱氨酸原料药粒径为100-150μm。
进一步地,所述防潮基质包括以下重量份组分:10-20份疏水性氨基酸以及10-30份分散剂。
更进一步地,所述疏水性氨基酸选自色氨酸、苯丙氨酸、缬氨酸、丙氨酸和蛋氨酸中的一种或多种。
更进一步地,所述疏水性氨基酸选自重量比为1∶1-2的色氨酸和缬氨酸的混合物。
更进一步地,所述分散剂选自α-半乳糖、右旋糖酐、季戊四醇、蔗糖中的一种或多种。
优选的,所述分散剂为α-半乳糖。
进一步地,所述隔离基质包括以下重量份组分:0.1-0.6份羟丙甲纤维素、0.01-0.05份聚乙二醇6000、滑石粉0.1-0.2份、乙醇7-12份。
进一步地,所述药学上可接受轴料包括但不限于山梨醇、阿司帕坦、日落黄、甜橙粉。
更进一步地,所述乙酰半胱氨酸颗粒,包括以下重量份组分:10份乙酰半胱氨酸原料药、20-50份防潮基质、7-13份隔离基质、100-200份山梨醇、0.1-1份阿司帕坦、0.01-0.05份日落黄以及0.1-1份甜橙粉末。
本发明进一步提供上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)防潮基质与乙酰半胱氨酸原料药加水润湿,研磨后干燥,得到混合物1;
(2)将隔离基质混合后溶解,对混合物1进行包衣,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸与药学上可接受的辅料混合造粒,得到乙酰半胱氨酸颗粒。
进一步地,所述步骤(1)中加水量以能完全够润湿防潮基质和乙酰半胱氨酸原料药为准。
进一步地,所述步骤(1)中干燥为喷雾干燥。
更进一步地,所述步骤(1)中喷雾干燥条件为:进风温度90-100℃,出风温度70-85℃,雾化压力160-180KPa。
进一步地,所述步骤(2)中隔离基质溶解于水中,隔离基质与水的重量比为7-13∶1-2。
更进一步地,控制步骤(2)中包衣温度为32-35℃。
进一步地,所述步骤(3)中造粒方式为干法造粒。
本发明的有益效果是:
1、本发明采用防潮基质和隔离基质双重基质对乙酰半胱氨酸原料药进行处理,不仅能够避免原料药吸潮,还能降低原料药的酸臭味,并且颗粒细腻,不易结块。
2、本发明采用疏水性氨基酸和分散剂作为防潮基质,其中分散剂起到润滑分散的作用,降低乙酰半胱氨酸与疏水性氨基酸之间的界面张力,而疏水性氨基酸分散在乙酰半胱氨酸原料药外部,避免空气中水分进入而引起乙酰半胱氨酸吸潮。尤其是当疏水性氨基酸为色氨酸和缬氨酸的混合物,分散剂为α-半乳糖时,对于降低乙酰半胱氨酸的引湿性有良好的效果。
3、本发明在乙酰半胱氨酸和防潮基质外先进行包衣处理,能够将原料药的酸臭味有效包裹其中,减少药物酸臭味道;同时通过山梨醇、香橙粉末等矫味剂的作用,进一步抵消乙酰半胱氨酸的酸臭味,使得最终制备得到的乙酰半胱氨酸具有良好的味道,提高患者顺应性。
具体实施方式
实施例1
本实施例乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)色氨酸、缬氨酸、α-半乳糖与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度95℃,出风温度80℃,雾化压力170KPa,得到混合物1;
(2)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加1.5份水溶解,对混合物1进行包衣,温度控制在35℃,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
实施例2
本实施例乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)色氨酸、缬氨酸、α-半乳糖与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度100℃,出风温度85℃,雾化压力180KPa,得到混合物1;
(2)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加2份水溶解,对混合物1进行包衣,温度控制在35℃,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
实施例3
本实施例乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)色氨酸、缬氨酸、季戊四醇与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度90℃,出风温度70℃,雾化压力160KPa,得到混合物1;
(2)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加1份水溶解,对混合物1进行包衣,温度控制在32℃,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
实施例4
本实施例乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)色氨酸、缬氨酸、右旋糖酐与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度95℃,出风温度80℃,雾化压力170KPa,得到混合物1;
(2)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加1.5份水溶解,对混合物1进行包衣,温度控制在35℃,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
实施例5
本实施例乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)苯丙氨酸、缬氨酸、α-半乳糖与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度95℃,出风温度80℃,雾化压力170KPa,得到混合物1;
(2)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加1.5份水溶解,对混合物1进行包衣,温度控制在35℃,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
实施例6
本实施例乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)色氨酸、丙氨酸、α-半乳糖与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度95℃,出风温度80℃,雾化压力170KPa,得到混合物1;
(2)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加1.5份水溶解,对混合物1进行包衣,温度控制在35℃,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
实施例7
本实施例乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)色氨酸、缬氨酸、蛋氨酸、α-半乳糖与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度95℃,出风温度80℃,雾化压力170KPa,得到混合物1;
(2)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加1.5份水溶解,对混合物1进行包衣,温度控制在35℃,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
实施例8
本实施例乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)丙氨酸、α-半乳糖与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度95℃,出风温度80℃,雾化压力170KPa,得到混合物1;
(2)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加1.5份水溶解,对混合物1进行包衣,温度控制在35℃,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
对比例1
不采用隔离基质,只采用防潮基质,其余均同实施例1,具体如下:
乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)色氨酸、缬氨酸、α-半乳糖与乙酰半胱氨酸原料药加水,使所有粉末完全润湿,研磨后喷雾干燥,进风温度95℃,出风温度80℃,雾化压力170KPa,得到混合物1;
(2)将混合物1于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
对比例2
不采用防潮基质,只采用隔离基质,具体如下
乙酰半胱氨酸颗粒包括以下组分:
上述乙酰半胱氨酸颗粒的制备方法,包括以下步骤:
(1)将羟丙甲纤维素、聚乙二醇6000、滑石粉、乙醇混合后,加1.5份水溶解,对乙酰半胱氨酸原料药进行包衣,温度控制在35℃,得到乙酰半胱氨酸药丸;
(2)将乙酰半胱氨酸药丸于30℃真空干燥后与山梨醇、阿司帕坦、日落黄、甜橙粉末混合均匀,干法造粒,得到乙酰半胱氨酸颗粒。
实验例1乙酰半胱氨酸颗粒湿稳定性研究
将实施例1-8,对比例1-2的乙酰半胱氨酸颗粒置于温度40±2℃,相对湿度75±5%条件下6个月后测定其含量、有关物质、干燥失重,具体方案按照《中国药典2020版》(第二部),乙酰半胱氨酸颗粒项下有关规定进行测定,具体结果见表1。
同时,对各乙酰半胱氨酸颗粒的味道、外观进行测定,结果见表1。
表1不同乙酰半胱氨酸颗粒湿稳定性
由表1数据可以看出,本发明实施例1-8在高湿环境下均能保持良好的稳定性,尤其是实施例1-4的效果更佳,其中实施例1-2的效果最佳。
实施例3和4分别采用季戊四醇和右旋糖酐作为防潮基质的分散剂,相对实施例1和2而言,二者的有效成分的含量有些许下降,可能是由于颗粒剂中含水量增加而引起有效成分含量相对减少,说明季戊四醇和右旋糖酐作为分散剂会在一定程度上降低乙酰半胱氨酸颗粒对湿的稳定性。
实施例5-8分别采用(苯丙氨酸和缬氨酸)、(色氨酸和丙氨酸)、(色氨酸、缬氨酸和蛋氨酸)、(丙氨酸),最终乙酰半胱氨酸颗粒的有效成分含量均有一定程度下降、有关物质含量增加、干燥失重增加,说明不同的疏水性氨基酸对于乙酰半胱氨酸颗粒的防潮效果并不相同,采用质量比为1∶1-2的色氨酸和缬氨酸时效果最佳。
对比例1不设有隔离基质、对比例2不设有防潮基质,乙酰半胱氨酸颗粒的各项指标均发生显著变化,说明本发明采用隔离基质和防潮基质能够有效避免乙酰半胱氨酸的引湿性和酸臭味,并且颗粒状态良好,不易发生结块现象。
上述详细说明是针对本发明其中之一可行实施例的具体说明,该实施例并非用以限制本发明的专利范围,凡未脱离本发明所为的等效实施或变更,均应包含于本发明技术方案的范围内。
Claims (3)
1.一种乙酰半胱氨酸颗粒,其特征在于,所述颗粒包括以下重量份组分:10份乙酰半胱氨酸原料药、20-50份防潮基质、7-13份隔离基质、100-200份山梨醇、0.1-1份阿司帕坦、0.01-0.05份日落黄以及0.1-1份甜橙粉末;
所述乙酰半胱氨酸原料药粒径为100-150μm;
所述防潮基质包括以下重量份组分:10-20份疏水性氨基酸以及10-30份分散剂;其中,疏水性氨基酸选自色氨酸、苯丙氨酸、缬氨酸、丙氨酸和蛋氨酸中的一种或多种;分散剂选自α-半乳糖、右旋糖酐、季戊四醇、蔗糖中的一种或多种;
所述隔离基质包括以下重量份组分:0.1-0.6份羟丙甲纤维素、0.01-0.05份聚乙二醇6000、滑石粉0.1-0.2份、乙醇7-12份;
所述乙酰半胱氨酸颗粒的制备方法包括以下步骤:
(1)防潮基质与乙酰半胱氨酸原料药加水润湿,研磨后干燥,得到混合物1;
(2)将隔离基质混合后溶解,对混合物1进行包衣,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸与山梨醇、阿司帕坦、日落黄以及甜橙粉末混合造粒,得到乙酰半胱氨酸颗粒。
2.一种权利要求1所述乙酰半胱氨酸颗粒的制备方法,其特征在于,包括以下步骤:
(1)防潮基质与乙酰半胱氨酸原料药加水润湿,研磨后干燥,得到混合物1;
(2)将隔离基质混合后溶解,对混合物1进行包衣,得到乙酰半胱氨酸药丸;
(3)将乙酰半胱氨酸药丸与山梨醇、阿司帕坦、日落黄以及甜橙粉末混合造粒,得到乙酰半胱氨酸颗粒。
3.根据权利要求2所述的乙酰半胱氨酸颗粒的制备方法,其特征在于,所述步骤(2)中隔离基质溶解于水中,隔离基质与水的重量比为7-13:1-2。
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