CN117122701B - 一种氯化钾颗粒制剂及其制备方法 - Google Patents
一种氯化钾颗粒制剂及其制备方法 Download PDFInfo
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- CN117122701B CN117122701B CN202311026669.3A CN202311026669A CN117122701B CN 117122701 B CN117122701 B CN 117122701B CN 202311026669 A CN202311026669 A CN 202311026669A CN 117122701 B CN117122701 B CN 117122701B
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- CN
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- Prior art keywords
- potassium chloride
- preparation
- cyclodextrin
- glucosyl
- calcium
- Prior art date
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- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 title claims abstract description 210
- 239000001103 potassium chloride Substances 0.000 title claims abstract description 105
- 235000011164 potassium chloride Nutrition 0.000 title claims abstract description 105
- 238000002360 preparation method Methods 0.000 title claims abstract description 70
- 239000008187 granular material Substances 0.000 title claims abstract description 42
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 24
- 239000001736 Calcium glycerylphosphate Substances 0.000 claims abstract description 17
- UHHRFSOMMCWGSO-UHFFFAOYSA-L calcium glycerophosphate Chemical compound [Ca+2].OCC(CO)OP([O-])([O-])=O UHHRFSOMMCWGSO-UHFFFAOYSA-L 0.000 claims abstract description 17
- 229940095618 calcium glycerophosphate Drugs 0.000 claims abstract description 17
- 235000019299 calcium glycerylphosphate Nutrition 0.000 claims abstract description 17
- 239000000796 flavoring agent Substances 0.000 claims abstract description 9
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 9
- 239000000314 lubricant Substances 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 22
- 238000002156 mixing Methods 0.000 claims description 20
- 239000011812 mixed powder Substances 0.000 claims description 16
- 238000009472 formulation Methods 0.000 claims description 12
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- 239000001116 FEMA 4028 Substances 0.000 claims description 11
- 229960004853 betadex Drugs 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 8
- 238000000227 grinding Methods 0.000 claims description 8
- 108010011485 Aspartame Proteins 0.000 claims description 6
- 239000000605 aspartame Substances 0.000 claims description 6
- 235000010357 aspartame Nutrition 0.000 claims description 6
- 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 6
- 229960003438 aspartame Drugs 0.000 claims description 6
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 235000019202 steviosides Nutrition 0.000 claims description 6
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims description 5
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 claims description 5
- 229940043377 alpha-cyclodextrin Drugs 0.000 claims description 5
- 229960001462 sodium cyclamate Drugs 0.000 claims description 5
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 4
- 229960004998 acesulfame potassium Drugs 0.000 claims description 4
- 239000000619 acesulfame-K Substances 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 4
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- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 3
- 239000004383 Steviol glycoside Substances 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
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- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 3
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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 claims description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 2
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- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 claims description 2
- PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
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- 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 claims description 2
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- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 claims 1
- LNMAXKMUGYXKPJ-UHFFFAOYSA-L calcium;1,1-dioxo-1,2-benzothiazol-2-id-3-one Chemical compound [Ca+2].C1=CC=C2C([O-])=NS(=O)(=O)C2=C1.C1=CC=C2C([O-])=NS(=O)(=O)C2=C1 LNMAXKMUGYXKPJ-UHFFFAOYSA-L 0.000 claims 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Abstract
本发明公开了一种氯化钾颗粒制剂及其制备方法,属于医药制剂技术领域,该颗粒制剂具体包括氯化钾包合物,甘油磷酸钙,润滑剂和矫味剂;其中,所述氯化钾包合物包括氯化钾和葡糖基‑环糊精。本发明氯化钾颗粒制剂制备工艺顺畅,含量均匀度高,易于分次用药,保证患者用药的安全有效,适合工业化大规模生产。
Description
技术领域
本发明属于医药制剂技术领域,具体地说,涉及一种氯化钾颗粒制剂及其制备方法。
背景技术
氯化钾是临床常用的电解质平衡调节药,临床疗效确切,广泛用于治疗和预防各种原因(进食不足、呕吐、严重腹泻、应用排钾利尿药或长期应用糖皮质刺激素和肾上腺皮质刺激素、失钾性肾病、Bartter综合症等)引起的低钾血症,亦可用于心、肾性水肿以及洋地黄等强心甙中毒引起的频发性、多源性早搏或快速心率失常等。
目前国内上市的氯化钾制剂有注射液、口服溶液、片剂、颗粒剂以及缓释制剂等,根据便携性以及生物利用度的优势,颗粒剂在固体制剂中占有比较大的市场,因此本发明主要针对氯化钾颗粒制剂进行了大量研究。
氯化钾原料具有以下特性:易溶于水、醚、甘油及碱类,微溶于乙醇,但不溶于无水乙醇,有吸湿性,易结块,在氯化钾混合过程中,由于强引湿性,即便控制房间的湿度≤35%,氯化钾表面仍会形成一层水膜,加入助流剂后不容易着色,导致着色剂加入后再混合会形成一定的色素块,外观看起来有黑色的小颗粒或者有明显的色素颗粒,这样会造成含量均匀度较差,且外观尽管符合药典标准,但仍会造成病人一定的不顺应性。
氯化钾对胃肠道有刺激性,常常引起恶心、呕吐、腹部的不适和腹泻。大剂量时可能引起虚弱、软弱无力、精神混乱、低血压、眩晕、心脏传导阻滞,甚至引起死亡。当服用氯化钾时会经常出现中毒的信号,因此对于普通制剂必须十分细心的给药,为了达到治疗目的,每天1-2g的氯化钾剂量常常需分2-6次服用。因此,获得一种含量均匀度高、质量稳定、易于分次服药的氯化钾颗粒制剂是十分必要的。
发明内容
鉴于此,本发明提供一种氯化钾颗粒制剂,旨在解决由于氯化钾吸湿性和易结块带来的制备工艺不顺畅和含量均匀度差的问题,同时能减少颗粒制剂被包装袋内表面吸附,降低患者分次用药时分量的难度。本发明氯化钾颗粒制剂制备工艺顺畅,含量均匀度高,易于分次用药,保证患者服用的安全有效,适合工业化大规模生产。
本发明提供一种氯化钾颗粒制剂,具体包括氯化钾包合物,甘油磷酸钙,润滑剂和矫味剂;其中,所述氯化钾包合物包括氯化钾和葡糖基-环糊精。
本发明氯化钾颗粒制剂中氯化钾原料具有吸湿性,易结块的性质,导致氯化钾在混合过程中,由于其强引湿性,即便控制房间的湿度≤35%,氯化钾表面仍会形成一层水膜,这给氯化钾颗粒制剂的制备以及保证其具有良好的含量均匀度带来极大的挑战,并且制得的颗粒制剂在灌装后易被包装袋内表面吸附,这也会给患者的分次用药带来很大的困难。发明人为解决上述问题,经过大量的研究发现,将氯化钾与葡糖基-环糊精先制成包合物的形式,并配合甘油磷酸钙制成颗粒制剂,可以解决以上问题,能够提高氯化钾颗粒制剂的含量均匀度以及制备工艺过程中的顺畅性,减少颗粒制剂被包装袋内表面吸附,降低患者分次用药时分量的难度。
上述的氯化钾颗粒制剂中,为了使得到的氯化钾包合物有更好的包封率,所述葡糖基-环糊精选自葡糖基-α-环糊精,葡糖基-β-环糊精,二葡糖基-β-环糊精中的一种。
上述的氯化钾颗粒制剂中,所述氯化钾与葡糖基-环糊精的质量用量比为1:1-3。
上述的氯化钾颗粒制剂中,所述润滑剂选自硬脂酸镁,硬脂富马酸钠,微粉硅胶,滑石粉中的一种或几种。
上述的氯化钾颗粒制剂中,所述矫味剂包括但不限于糖、糖精钠、糖精钙、甜蜜素、甜菊糖苷、甘草甜、环己烷氨基磺酸、环己烷氨基磺酸钠、天冬酰胺、二氢查耳酮、醇糖、天冬甜精、三氯蔗糖、安塞蜜、阿斯巴甜、香橙香精、草莓香精等中的一种或几种。
上述的氯化钾颗粒制剂中,各组分的用量以质量份数计为:氯化钾为1份,葡糖基-环糊精为1-3份,甘油磷酸钙为0.3-1份,润滑剂为0.02-0.1份,矫味剂为0.06-0.3份。
上述的氯化钾颗粒制剂中,还包括稀释剂,所述稀释剂包括但不限于乳糖,微晶纤维素,甘露醇,预胶化淀粉,磷酸氢钙,山梨醇,蔗糖,硫酸钙,碳酸钙中的一种或几种。所述稀释剂的用量可根据本领域技术人员的一般认知水平得到。
上述的氯化钾颗粒制剂中,还包括崩解剂,所述崩解剂包括但不限于交联羧甲基纤维素钠,交联聚维酮,羧甲基淀粉钠,低取代羟丙基纤维素中的一种或几种。所述崩解剂的用量可根据本领域技术人员的一般认知水平得到。
本发明还提供一种上述氯化钾颗粒制剂的制备方法,方法包括以下步骤:
(1)将氯化钾和葡糖基-环糊精混合得混粉,加入混粉总重量3-5倍量的水,充分研磨,干燥,得氯化钾包合物;
(2)向氯化钾包合物中加入甘油磷酸钙、润滑剂和矫味剂混合均匀,装袋,得氯化钾颗粒制剂。
上述氯化钾颗粒制剂的制备方法,所述步骤(2)中可选择性加入崩解剂,稀释剂中的一种或两种。
与现有技术相比,本发明的有益效果为:
本发明通过将氯化钾与葡糖基-环糊精制成氯化钾包合物,再配合甘油磷酸钙制成颗粒制剂,克服了因氯化钾吸湿性和易结块带来的制备工艺不顺畅和含量均匀度差的问题,同时能减少颗粒制剂被包装袋内表面吸附,降低患者分次用药时分量的难度,保证患者用药安全。
具体实施方式
实施例1
组成 | 用量(g) |
氯化钾 | 1 |
葡糖基-α-环糊精 | 2 |
甘油磷酸钙 | 0.6 |
硬脂酸镁 | 0.04 |
甜菊糖苷 | 0.12 |
制备方法:
(1)将氯化钾和葡糖基-α-环糊精混合得混粉,加入混粉总重量3倍量的水,充分研磨,干燥,得氯化钾包合物;
(2)向氯化钾包合物中加入甘油磷酸钙、硬脂酸镁和甜菊糖苷混合均匀,装袋,得氯化钾颗粒制剂。
实施例2
制备方法:
(1)将氯化钾和葡糖基-α-环糊精混合得混粉,加入混粉总重量5倍量的水,充分研磨,干燥,得氯化钾包合物;
(2)向氯化钾包合物中加入甘油磷酸钙、硬脂富马酸钠和阿斯巴甜混合均匀,装袋,得氯化钾颗粒制剂。
实施例3
组成 | 用量(g) |
氯化钾 | 1 |
葡糖基-β-环糊精 | 1 |
甘油磷酸钙 | 0.3 |
硬脂酸镁 | 0.01 |
微粉硅胶 | 0.01 |
安塞蜜 | 0.06 |
制备方法:
(1)将氯化钾和葡糖基-β-环糊精混合得混粉,加入混粉总重量4倍量的水,充分研磨,干燥,得氯化钾包合物;
(2)向氯化钾包合物中加入甘油磷酸钙、硬脂酸镁、微粉硅胶和安塞蜜混合均匀,装袋,得氯化钾颗粒制剂。
实施例4
制备方法:
(1)将氯化钾和二葡糖基-β-环糊精混合得混粉,加入混粉总重量3倍量的水,充分研磨,干燥,得氯化钾包合物;
(2)向氯化钾包合物中加入甘油磷酸钙、乳糖、交联聚维酮、滑石粉和安塞蜜混合均匀,装袋,得氯化钾颗粒制剂。
实施例5
组成 | 用量(g) |
氯化钾 | 1 |
葡糖基-β-环糊精 | 3 |
甘油磷酸钙 | 0.8 |
预胶化淀粉 | 3 |
磷酸氢钙 | 2 |
羧甲基淀粉钠 | 0.4 |
硬脂酸镁 | 0.08 |
阿斯巴甜 | 0.1 |
香橙香精 | 0.1 |
制备方法:
(1)将氯化钾和葡糖基-β-环糊精混合得混粉,加入混粉总重量5倍量的水,充分研磨,干燥,得氯化钾包合物;
(2)向氯化钾包合物中加入甘油磷酸钙、预胶化淀粉、磷酸氢钙、羧甲基淀粉钠、硬脂酸镁、阿斯巴甜和香橙香精混合均匀,装袋,得氯化钾颗粒制剂。
实施例6
组成 | 用量(g) |
氯化钾 | 1 |
葡糖基-β-环糊精 | 2 |
甘油磷酸钙 | 0.7 |
微晶纤维素 | 5 |
低取代羟丙基纤维素 | 0.2 |
交联羧甲基纤维素钠 | 0.2 |
硬脂酸镁 | 0.08 |
硬脂酸 | 0.01 |
甜蜜素 | 0.3 |
制备方法:
(1)将氯化钾和葡糖基-β-环糊精混合得混粉,加入混粉总重量4倍量的水,充分研磨,干燥,得氯化钾包合物;
(2)向氯化钾包合物中加入甘油磷酸钙、微晶纤维素、低取代羟丙基纤维素、交联羧甲基纤维素钠、硬脂酸镁、硬脂酸和甜蜜素混合均匀,装袋,得氯化钾颗粒制剂。
对比例
制备方法同实施例1。
对比例4
组成 | 用量(g) |
氯化钾 | 1 |
甘油磷酸钙 | 0.6 |
硬脂酸镁 | 0.04 |
甜菊糖苷 | 0.12 |
制备方法:
将氯化钾和甘油磷酸钙、硬脂酸镁和甜菊糖苷混合均匀,装袋,得氯化钾颗粒制剂。
休止角试验
采用粉末颗粒流动性分析仪(型号FT-104BA)测定实施例1-6和对比例1-4中氯化钾颗粒制剂的休止角,结果如下:
由以上数据可知,实施例1-6的氯化钾颗粒制剂样品具有较小的休止角,流动性优异,患者分次用药时易分量,保证患者的用药安全。对比例1-2未采用葡糖基-环糊精制备包合物,对比例3中未加入甘油磷酸钙,对比例4未制成包合物,对比例1-4得到的氯化钾颗粒制剂样品流动性不好,患者分次用药的分量不准确。
吸附性考察
将实施例1-6及对比例1-4得到的氯化钾颗粒制剂样品进行分量,观察是否有颗粒制剂被包装袋内表面吸附现象,结果如下:
实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | |
结论 | 无吸附 | 无吸附 | 无吸附 | 无吸附 | 无吸附 |
实施例6 | 对比例1 | 对比例2 | 对比例3 | 对比例4 | |
结论 | 无吸附 | 少量吸附 | 少量吸附 | 少量吸附 | 大量吸附 |
由以上数据可知,实施例1-6的氯化钾颗粒制剂无被包装袋内表面吸附现象,患者分次用药时易分量,保证患者的用药安全。
含量均匀度考察
取实施例1-6和对比例1-4制得的氯化钾颗粒制剂样品,在6个点分别取样测定平均含量(%),并计算6个点的含量的RSD,含量测定方法:电位滴定法,结果如下:
由以上数据可知,实施例1-6的氯化钾颗粒制剂含量均匀度好,患者分次用药时易分量,保证患者的用药安全。
Claims (8)
1.一种氯化钾颗粒制剂,其特征在于,包括氯化钾包合物,甘油磷酸钙,润滑剂和矫味剂;其中,所述氯化钾包合物包括氯化钾和葡糖基-环糊精;各组分的用量以质量份数计为:氯化钾为1份,葡糖基-环糊精为1-3份,甘油磷酸钙为0.3-1份,润滑剂为0.02-0.1份,矫味剂为0.06-0.3份。
2.根据权利要求1所述的氯化钾颗粒制剂,其特征在于,所述葡糖基-环糊精选自葡糖基-α-环糊精,葡糖基-β-环糊精,二葡糖基-β-环糊精中的一种。
3.根据权利要求1所述的氯化钾颗粒制剂,其特征在于,所述润滑剂选自硬脂酸镁,硬脂富马酸钠,微粉硅胶,滑石粉中的一种或几种。
4.根据权利要求1所述的氯化钾颗粒制剂,其特征在于,所述矫味剂为糖,糖精钠,糖精钙,甜蜜素,甜菊糖苷,天冬酰胺,二氢查耳酮,三氯蔗糖,安塞蜜,阿斯巴甜中的一种或几种。
5.根据权利要求1所述的氯化钾颗粒制剂,其特征在于,还包括稀释剂,所述稀释剂选自乳糖,微晶纤维素,甘露醇,预胶化淀粉,磷酸氢钙,山梨醇,蔗糖,硫酸钙,碳酸钙中的一种或几种。
6.根据权利要求1所述的氯化钾颗粒制剂,其特征在于,还包括崩解剂,所述崩解剂选自交联羧甲基纤维素钠,交联聚维酮,羧甲基淀粉钠,低取代羟丙基纤维素中的一种或几种。
7.一种权利要求1所述氯化钾颗粒制剂的制备方法,其特征在于,方法包括以下步骤:
(1)将氯化钾和葡糖基-环糊精混合得混粉,加入混粉总重量3-5倍量的水,充分研磨,干燥,得氯化钾包合物;
(2)向氯化钾包合物中加入甘油磷酸钙、润滑剂和矫味剂混合均匀,装袋,得氯化钾颗粒制剂。
8.根据权利要求7所述氯化钾颗粒制剂的制备方法,其特征在于,所述步骤(2)中可选择性加入崩解剂,稀释剂中的一种或两种。
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CN103565750A (zh) * | 2013-09-30 | 2014-02-12 | 北京德众万全药物技术开发有限公司 | 消旋卡多曲颗粒及其制备方法 |
CN109125280A (zh) * | 2018-10-28 | 2019-01-04 | 广州誉东健康制药有限公司 | 一种氯化钾缓释制剂及其制备方法 |
CN115040484A (zh) * | 2022-05-20 | 2022-09-13 | 浙江和沐康医药科技有限公司 | 一种粉末直接灌装的氯化钾颗粒剂及制备方法 |
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HK1051320A1 (zh) * | 1999-12-16 | 2003-08-01 | Eurand America Incorporated | 氯化鉀控釋片的配方 |
CN103565750A (zh) * | 2013-09-30 | 2014-02-12 | 北京德众万全药物技术开发有限公司 | 消旋卡多曲颗粒及其制备方法 |
CN109125280A (zh) * | 2018-10-28 | 2019-01-04 | 广州誉东健康制药有限公司 | 一种氯化钾缓释制剂及其制备方法 |
CN115040484A (zh) * | 2022-05-20 | 2022-09-13 | 浙江和沐康医药科技有限公司 | 一种粉末直接灌装的氯化钾颗粒剂及制备方法 |
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