CN116459211A - 一种盐酸奥洛他定口服溶液及制备方法 - Google Patents
一种盐酸奥洛他定口服溶液及制备方法 Download PDFInfo
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- CN116459211A CN116459211A CN202310318228.4A CN202310318228A CN116459211A CN 116459211 A CN116459211 A CN 116459211A CN 202310318228 A CN202310318228 A CN 202310318228A CN 116459211 A CN116459211 A CN 116459211A
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- olopatadine hydrochloride
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- HVRLZEKDTUEKQH-NOILCQHBSA-N Olopatadine hydrochloride Chemical compound Cl.C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 HVRLZEKDTUEKQH-NOILCQHBSA-N 0.000 title claims abstract description 71
- 229960003139 olopatadine hydrochloride Drugs 0.000 title claims abstract description 70
- 229940100688 oral solution Drugs 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000003755 preservative agent Substances 0.000 claims abstract description 19
- 230000002335 preservative effect Effects 0.000 claims abstract description 19
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- 239000002562 thickening agent Substances 0.000 claims abstract description 19
- 125000003118 aryl group Chemical group 0.000 claims abstract description 18
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 14
- 235000011187 glycerol Nutrition 0.000 claims abstract description 14
- 239000003765 sweetening agent Substances 0.000 claims abstract description 14
- 239000000796 flavoring agent Substances 0.000 claims abstract description 11
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 3
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- 238000012360 testing method Methods 0.000 description 19
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 239000002245 particle Substances 0.000 description 14
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- 239000001509 sodium citrate Substances 0.000 description 6
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 6
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- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
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- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
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- 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 description 1
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- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000003141 Tachykinin Human genes 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
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- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
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- 238000001647 drug administration Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
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- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
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- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229960004114 olopatadine Drugs 0.000 description 1
- JBIMVDZLSHOPLA-LSCVHKIXSA-N olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 JBIMVDZLSHOPLA-LSCVHKIXSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
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- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
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- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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Abstract
本发明属于医药领域,本发明公开一种盐酸奥洛他定口服溶液及制备方法,其主要用于治疗过敏性鼻炎、荨麻疹、瘙痒性皮肤病。起到治疗作用的活性成分为盐酸奥洛他定,辅料成分包含溶剂、防腐剂、矫味剂、增稠剂、pH调节剂。其中盐酸奥洛他定浓度为0.25‑2mg/ml,防腐剂浓度为0.1‑10mg/ml,矫味剂包含甜味剂及芳香剂,甜味剂浓度为50‑600mg/ml,芳香剂浓度为0.1‑3mg/ml,增稠剂浓度为0.5‑5mg/ml,溶剂包含甘油及纯化水,采用pH调节剂控制pH值为4.0‑7.5。盐酸奥洛他定口服溶液的开发能够改善老人、儿童等吞食困难群体的用药依从性,同时不涉及片剂及颗粒剂的崩解分散过程而提高了药物吸收及分布速度。
Description
技术领域
本发明涉及一种药用口服溶液。具体而言,本品发明涉及一种治疗过敏性鼻炎、荨麻疹瘙痒性皮肤病(湿疹、皮炎、痒疹、皮肤瘙痒症、寻常性银屑病、渗出性多形红斑)的口服溶液,其活性成分为盐酸奥洛他定。
背景技术
盐酸奥洛他定是由日本协和发酵公司开发并上市的抗过敏药,先后在欧、美、日等多国上市,主要的临床作用和功效就是抗组胺、抗过敏,治疗过敏性鼻炎、过敏性结膜炎、过敏性哮喘、虫咬性皮炎、皮肤病(湿疹、皮肤炎、痒疹、皮肤瘙痒症、寻常型干癣、多形性渗出性红斑)伴发的瘙痒特异性皮炎、荨麻疹等与过敏反应密切相关的各种疾病。
我国国家药品监督管理局公布的盐酸奥洛他定剂型包含片剂、胶囊剂、滴眼剂、颗粒剂。片剂、胶囊剂规格均为5mg,颗粒剂规格为2.5mg。国内外均未见盐酸奥洛他定口服溶液剂型上市。
盐酸奥洛他定作为一种新型的相对选择性高的抗过敏药,能够抑制速激肽及其它化学递质,如组胺、花生四烯酸、血栓素、白三烯等的释放。盐酸奥洛他定既能够抑制肥大细胞释放组胺,又对选择性较高的H1受体拮抗具有双重抑制作用,因此,其作用效果好。盐酸奥洛他定能抑制入角皮细胞释放组胺,它对α肾上腺素受体,多巴胺受体,M1、M2受体无作用,因此,其副作用少。滴眼液主要用于过敏性结膜炎的体征和症状,用于局部治疗;而已上市的奥洛他定片剂、颗粒剂型在服用后涉及药物的崩解释放,不及口服溶液吸收分布快,同时盐酸奥洛他定口服溶液可提高老人、儿童等吞食困难群体的用药依从性。
发明内容
盐酸奥洛他定口服溶液作为盐酸奥洛他定的新剂型,本发明着重对药物制剂的处方工艺进行开发,涉及主药的浓度,载体辅料的种类用量及生产工艺的开发及控制。
盐酸奥洛他定口服溶液选用的载体辅料包含溶剂、防腐剂、矫味剂、增稠剂、pH调节剂,溶剂选择甘油及纯化水的一种或多种。防腐剂为苯甲酸钠、羟苯甲酯、羟苯丙酯、羟苯乙酯、山梨酸钾、苯甲醇等一种或多种。矫味剂包含甜味剂及芳香剂,甜味剂可为山梨醇、蔗糖、三氯蔗糖、糖精钠等的一种或多种,芳香剂为奶油香精、桔子香精、薄荷香精、水蜜桃香精、草莓香精等的一种。增稠剂选用羟乙基纤维素、海藻糖等的一种或多种。pH调节剂选用枸橼酸、枸橼酸钠等的一种或多种。
根据现有盐酸奥洛他定上市剂型规格、用量,同时着重考虑儿童可服用剂量的局限性确定盐酸奥洛他定口服溶液含主成分盐酸奥洛他定浓度为0.25-2mg/ml,优选0.5-1mg/ml,更优选1mg/ml。
通过处方对比研究,加入增稠剂可改变药物制剂的润喉感,可提高小儿患者的顺应性,其增稠剂用量为0.5-5mg/ml。
矫味剂包含甜味剂及芳香剂。芳香剂作为矫味的重点辅料,针对儿童用药的顺应性,优选奶油香精或水蜜桃香精,其用量为0.1-3mg/ml,甜味剂浓度为50-600mg/ml。
所述溶剂为甘油及纯化水,甘油含量为50-800mg/ml。
防腐剂浓度为0.1-10mg/ml。
盐酸奥洛他定口服溶液的生产步骤:
(1):向配液罐内加入适量的纯化水;
(2):称取处方量的防腐剂投入罐中,搅拌至溶解;
(3):向配液罐内加入处方量的甘油搅拌混匀;
(4):向配液罐内加入芳香剂、增稠剂、部分pH值调节剂搅拌至溶解;
(5):向配液罐内加入盐酸奥洛他定,搅拌溶解;
(6):向配液罐内加入甜味剂,搅拌溶解;
(7):补充纯化水至90%;
(8):用pH调节剂控制pH值为4.0-7.5;
(9):补充纯化水至终体积,混匀;
(10):灌装。
附图说明
附图1盐酸奥洛他定口服溶液及原研盐酸奥洛他定颗粒长期试验有关物质趋势图
附图2盐酸奥洛他定口服溶液及原研盐酸奥洛他定颗粒长期试验含量趋势图
具体实施方式
以下结合实例对本发明进行进一步的详细说明,但本发明的范围并非仅限于这些实施例的范围。
实例一
增稠剂羟乙基纤维素用量的筛选,通过检测确定羟乙基纤维素对制剂质量的影响。
表1羟乙基纤维素用量的筛选处方信息
原辅料名称 | 处方一 | 处方二 | 处方三 | 处方四 |
盐酸奥洛他定 | 0.1g | 0.1g | 0.1g | 0.1g |
山梨醇 | 30g | 30g | 30g | 30g |
羟乙基纤维素 | / | 0.05g | 0.3g | 0.5g |
羟苯甲酯 | 0.1g | 0.1g | 0.1g | 0.1g |
羟苯丙酯 | 0.01g | 0.01g | 0.01g | 0.01g |
水蜜桃香精 | 0.1g | 0.1g | 0.1g | 0.1g |
甘油 | 15g | 15g | 15g | 15g |
枸橼酸钠 | 0.5g | 0.5g | 0.5g | 0.5g |
枸橼酸 | 适量 | 适量 | 适量 | 适量 |
加水至 | 100ml | 100ml | 100ml | 100ml |
制备过程
向配液罐内加入处方量60%的纯化水后称取处方量的防腐剂投入罐中,搅拌至溶解,溶解后向配液罐内加入处方量的甘油搅拌混匀,再向配液罐内加芳香剂、增稠剂、部分pH值调节剂搅拌至溶解,接着向配液罐内加盐酸奥洛他定搅拌溶解,最后向配液罐内加入甜味剂搅拌溶解;补充纯化水至90%;用枸橼酸或枸橼酸钠溶液控制pH值为4.0-7.5;补充纯化水至终体积,混匀,灌装。
表2羟乙基纤维素用量的筛选检测结果
检测结果表明,用羟乙基纤维素做增稠剂对制剂的有关物质及含量无明显影响,但不添加羟乙基纤维素制剂口感略差,为保证患者用药的依从性,增稠剂羟乙基纤维素的用量应控制在0.5-5mg/ml。
实例二
芳香剂种类及用量的筛选,考察不同芳香剂的种类对制剂的影响及可行性,并确定其用量范围。
表3芳香剂种类及用量的筛选处方信息
原辅料名称 | 处方五 | 处方六 | 处方七 | 处方八 | 处方九 |
盐酸奥洛他定 | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
山梨醇 | 30g | 30g | 30g | 30g | 30g |
羟乙基纤维素 | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
羟苯甲酯 | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
羟苯丙酯 | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
水蜜桃香精 | 0.01g | / | 0.05g | 0.1g | 0.3g |
薄荷香精 | / | 0.05g | / | / | / |
甘油 | 15g | 15g | 15g | 15g | 15g |
枸橼酸钠 | 0.8g | 0.8g | 0.8g | 0.8g | 0.8g |
枸橼酸 | 适量 | 适量 | 适量 | 适量 | 适量 |
加水至 | 100ml | 100ml | 100ml | 100ml | 100ml |
制备过程:
向配液罐内加入处方量60%的纯化水,向配液罐内加入处方量的甘油,称取处方量的芳香剂、防腐剂、增稠剂、部分pH调节剂依次投入罐中,搅拌至溶解,加入称量好的盐酸奥洛他定,搅拌溶解,补充纯化水至90%,用枸橼酸或枸橼酸钠溶液控制pH值为4.0-7.5,补充纯化水至100ml,混匀,灌装后进行考察。
表4芳香剂种类及用量的筛选检测结果
香精种类 | 香精用量 | 性状 | 有关物质总杂(%) | 口感 |
水蜜桃香精 | 0.1mg/ml | 无色澄清液体,有芳香气,味甜。 | 0.013 | 良好 |
薄荷香精 | 0.5mg/ml | 无色澄清液体,有芳香气,味甜。 | 0.012 | 良好 |
水蜜桃香精 | 0.5mg/ml | 无色澄清液体,有芳香气,味甜。 | 0.012 | 良好 |
水蜜桃香精 | 1.0mg/ml | 无色澄清液体,有芳香气,味甜。 | 0.011 | 较好 |
水蜜桃香精 | 3.0mg/ml | 无色澄清液体,有芳香气,味甜。 | 0.011 | 良好 |
结果显示,薄荷香精与水蜜桃香精对产品质量影响不大,可选用任意一种香精作为本品的芳香剂进行使用,同时也可选用儿童易接受的草莓香精,奶油香精进行本品的开发。水蜜桃香精用量考察结果显示,香精用量应控制为0.1-3mg/ml,更优选为1mg/ml。
实例三
制备自研处方盐酸奥洛他定口服溶液,与原研盐酸奥洛他定颗粒进行影响因素、加速试验、长期试验的稳定性研究,确定自研盐酸奥洛他定口服溶液的质量稳定性。
表5自研盐酸奥洛他定口服溶液处方信息
原辅料名称 | 用量 |
盐酸奥洛他定 | 1.0kg |
山梨醇 | 300kg |
羟乙基纤维素 | 3kg |
苯甲酸钠 | 2kg |
水蜜桃香精 | 1kg |
甘油 | 150kg |
枸橼酸钠 | 8kg |
枸橼酸 | 适量 |
加水至 | 1000L |
自研盐酸奥洛他定口服溶液生产工艺:
向配液罐内加入处方量60%的纯化水,向配液罐内加入处方量的防腐剂,搅拌溶解;加入处方量的甘油,搅拌混匀;再加入处方量的芳香剂、增稠剂、部分pH值调节剂搅拌至溶解;加入处方量的盐酸奥洛他定,搅拌溶解;向配液罐中加入甜味剂,搅拌溶解;补充纯化水至90%,用pH调节剂调节pH值为6.0,补充纯化水至终体积,混匀,灌装。
影响因素对比
盐酸奥洛他定颗粒及盐酸奥洛他定口服溶液均为口服制剂,颗粒剂一般用温水冲散后给药,与口服溶液剂型给药方式相对接近。因此将自制口服溶液与盐酸奥洛他定颗粒原研药(持证商:協和キリン株式会社,商品名:Allelock,规格:0.5%,0.5g/袋)进行同等对比研究,原料药作为参考。
表6盐酸奥洛他定口服溶液影响因素检测结果
表7原研盐酸奥洛他定颗粒影响因素检测结果
表8盐酸奥洛他原料影响因素检测结果
通过影响因素比对结果可知,自研盐酸奥洛他定口服溶液0天有关物质与原料基本一致,60℃10天有关物质明显小于原研盐酸奥洛他定颗粒有关物质,含量等项目符合标准要求,自研盐酸奥洛他定口服溶液的质量不低于原研盐酸奥洛他定颗粒。
加速试验
对自研盐酸奥洛他定口服溶液与原研盐酸奥洛他定颗粒进行加速试验质量对比,加速试验条件为:温度40℃±2℃,相对湿度:75%±5%,分别于0、1、2、3、6月取样。
表9自研盐酸奥洛他定口服溶液加速试验检测结果
表10原研盐酸奥洛他定颗粒加速试验检测结果
加速试验结果显示,盐酸奥洛他定口服溶液在加速试验条件下质量稳定,自研盐酸奥洛他定口服溶液加速6月有关物质总杂为0.131%,而原研盐酸奥洛他定颗粒加速6月有关物质总杂为0.254%,自研盐酸奥洛他定口服溶液总体质量优于原研盐酸奥洛他定颗粒。
长期试验
对自研盐酸奥洛他定口服溶液与原研盐酸奥洛他定颗粒进行长期试验质量对比,长期试验条件为:温度25℃±2℃,相对湿度:60%±5%,分别于0、3、6、9、12、18、24月取样。
表11自研盐酸奥洛他定口服溶液长期试验检测结果
表12原研盐酸奥洛他定颗粒长期试验检测结果
长期试验结果表明,盐酸奥洛他定口服溶液在长期试验25℃±2℃,相对湿度60%±5%条件下24月内相对稳定,质量可靠。对比原研盐酸奥洛他定颗粒,其有关物质增幅无明显差异。
本发明所制备的盐酸奥洛他定口服溶液,是一种无色至微黄色的澄清溶液,未添加不溶性辅料载体,不具有药物沉降的风险,也无影响药物吸收的辅料。并通过稳定性研究可知,该口服溶液具有较好的稳定性。
本发明通过处方及工艺的开发,得到了一种新剂型:盐酸奥洛他定口服溶液。此剂型存在巨大的市场价值,对比颗粒剂及片剂至少存在以下优点,颗粒剂及片剂与口服溶液均为口服给药,药物的吸收过程基本相似,但口服溶液在服用过程中不需要颗粒及片剂的崩解过程,从而会加快药物的吸收分布,更快的达到药效。此外,口服溶液中含有芳香剂及甜味剂,可提高儿童群体的依从性。同时可解决吞服困难群体用药的合理性。
Claims (5)
1.用于治疗过敏性鼻炎、荨麻疹、瘙痒性皮肤病的口服型组合物,其特征在于:活性成分为盐酸奥洛他定,辅料载体包含溶剂、防腐剂、矫味剂、增稠剂、pH调节剂;
所述活性成分:
溶解于溶液中的0.25mg/ml-2mg/ml浓度的盐酸奥洛他定,优选0.5-1mg/ml,更优选1mg/ml;
所述辅料载体:
防腐剂浓度为0.1-10mg/ml;
矫味剂包含甜味剂及芳香剂,甜味剂浓度为50-600mg/ml,芳香剂浓度为0.1-3mg/ml;
增稠剂浓度为0.5-5mg/ml;
所述溶剂为甘油及纯化水,甘油含量为50-800mg/ml;
组合物具有4.0-7.5pH值。
2.根据权利要求1所述的口服型组合物,其特征在于该剂型为口服溶液。
3.根据权利要求1所述的口服型组合物,其特征在于所述防腐剂优选苯甲酸钠,浓度为0.1-10mg/ml,优选为2mg/ml。
4.根据权利要求1所述的口服型组合物,其特征在于芳香剂优选水蜜桃香精,增稠剂优选羟乙基纤维素,甜味剂优选山梨醇。
5.所述的口服型组合物的制备方法,包括如下步骤:
(1):向配液罐内加入适量的纯化水;
(2):称取处方量的防腐剂投入罐中,搅拌至溶解;
(3):向配液罐内加入处方量的甘油搅拌混匀;
(4):向配液罐内加入芳香剂、增稠剂、部分pH值调节剂搅拌至溶解;
(5):向配液罐内加入盐酸奥洛他定,搅拌溶解;
(6):向配液罐内加入甜味剂,搅拌溶解;
(7):补充纯化水至90%;
(8):用pH调节剂控制pH值为4.0-7.5;
(9):补充纯化水至终体积,混匀;
(10):灌装。
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