CN114948887A - 一种克拉霉素分散片及其制备方法 - Google Patents
一种克拉霉素分散片及其制备方法 Download PDFInfo
- Publication number
- CN114948887A CN114948887A CN202210689177.1A CN202210689177A CN114948887A CN 114948887 A CN114948887 A CN 114948887A CN 202210689177 A CN202210689177 A CN 202210689177A CN 114948887 A CN114948887 A CN 114948887A
- Authority
- CN
- China
- Prior art keywords
- parts
- clarithromycin
- dispersible tablet
- sieving
- magnesium stearate
- 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
Links
- 229960002626 clarithromycin Drugs 0.000 title claims abstract description 54
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 title claims abstract description 54
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims description 14
- 239000000463 material Substances 0.000 claims abstract description 26
- 239000000853 adhesive Substances 0.000 claims abstract description 15
- 230000001070 adhesive effect Effects 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 38
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 33
- 238000007873 sieving Methods 0.000 claims description 24
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 21
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 21
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 21
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 21
- 238000002156 mixing Methods 0.000 claims description 20
- 235000019359 magnesium stearate Nutrition 0.000 claims description 19
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 16
- 229920002261 Corn starch Polymers 0.000 claims description 15
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 15
- 239000008120 corn starch Substances 0.000 claims description 15
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 15
- 239000000377 silicon dioxide Substances 0.000 claims description 14
- 235000012239 silicon dioxide Nutrition 0.000 claims description 14
- 229940083575 sodium dodecyl sulfate Drugs 0.000 claims description 14
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 13
- 229960000913 crospovidone Drugs 0.000 claims description 13
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 13
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 13
- 238000005303 weighing Methods 0.000 claims description 13
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
- 229920001353 Dextrin Polymers 0.000 claims description 6
- 239000004375 Dextrin Substances 0.000 claims description 6
- 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 6
- 229940099112 cornstarch Drugs 0.000 claims description 6
- 235000019425 dextrin Nutrition 0.000 claims description 6
- 239000007884 disintegrant Substances 0.000 claims description 6
- 229910002012 Aerosil® Inorganic materials 0.000 claims description 5
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 5
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 5
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
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- 238000000034 method Methods 0.000 claims description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 229940037627 magnesium lauryl sulfate Drugs 0.000 claims description 2
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims 1
- 229950005770 hyprolose Drugs 0.000 claims 1
- 229960003943 hypromellose Drugs 0.000 claims 1
- 239000000454 talc Substances 0.000 claims 1
- 229910052623 talc Inorganic materials 0.000 claims 1
- 239000003814 drug Substances 0.000 description 10
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 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 description 4
- 239000006185 dispersion Substances 0.000 description 4
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- 235000003599 food sweetener Nutrition 0.000 description 4
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- 239000003765 sweetening agent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229960003276 erythromycin Drugs 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 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 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000007779 soft material Substances 0.000 description 3
- 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 2
- 108010011485 Aspartame Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
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- 235000010357 aspartame Nutrition 0.000 description 2
- 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 description 2
- 229960003438 aspartame Drugs 0.000 description 2
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- 241000204031 Mycoplasma Species 0.000 description 1
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- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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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
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- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Life Sciences & Earth Sciences (AREA)
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- Veterinary Medicine (AREA)
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- Inorganic Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Medicinal Preparation (AREA)
Abstract
本发明提供了一种克拉霉素分散片，包括如下重量配比的原料及辅料：克拉霉素250份、填充剂120～200份、崩解剂30～80份、增溶剂1～10份、助流剂5～30份以及粘合剂10～40份，本发明采用特定的辅料，可以采用干法直接治粒压片，简化了制剂工艺。
Description
技术领域
本发明涉及制药技术领域，具体涉及一种克拉霉素分散片及其制备方法。
背景技术
克拉霉素(Clarithromycin)。别名：克拉仙；克拉红霉素。该药物为14元环大环内酯类抗生素，其机制是通过阻碍细胞核蛋白50S亚基的联结，抑制蛋白质的合成而产生抑菌作用。该药物对革兰阳性菌如金黄色葡萄球菌、链球菌、肺炎球菌等有抑制作用.对部分革兰阴性菌如流感嗜血杆菌、百日咳杆菌、淋病奈瑟菌、嗜肺军团菌和部分厌氧菌如脆弱拟杆菌、消化链球菌、痤疮丙酸杆菌等也有抑制作用。此外对支原体也有抑制作用。该药物特点为在体外的抗菌活性与红霉素相似。但在体内对部分细菌如金黄色葡萄球菌、链球菌、流感嗜虹杆菌等的抗菌活性比红霉素强。本品与红霉素之问有交叉耐药性。该药物适用于克拉霉素敏感菌所引起的下列感染：①鼻咽感染：扁桃体炎、咽炎、鼻窭炎；②下呼吸道感染：急性支气管炎、慢性支气管炎急性发作和肺炎；③皮肤软组织感染：脓疱病、丹毒、毛囊炎、疖和伤口感染；④急性中耳炎、肺炎支原体肺炎、沙眼衣原体引起的尿道炎及宫颈炎等；⑤也用于军团菌感染.或与其他药物联合用于鸟分枝杆菌感染、幽门螺杆菌感染的治疗(参见马振友，李斌，李元文主编,新编中西皮肤药物手册，河南科学技术出版社，第40页，2019.01)。克拉霉素不溶于水，制成分散片可以提高其生物利用度。现有技术中制备分散片的方法和技术已有，例如：CN106265552A(一种克拉霉素分散片的制备方法)，公开了一种克拉霉素分散片的制备方法，其特征在于：它包括如下步骤：a、称取各重量配比的原料及辅料：克拉霉素1-5份、填充剂4.7-8.7份、崩解剂0.5-1.5份、润滑剂0.05-0.25份、粘合剂0.05-0.1份；b、将克拉霉素和粘合剂溶于50-95％乙醇中,制备成含药粘合剂；c、取填充剂、润滑剂和崩解剂混合物过筛，混合；d、将b步骤的含药粘合剂加入到步骤(c)制备的混合物中，制粒、干燥、整粒、总混、压片，制备成片剂；所述填充剂选自淀粉、糊精、乳糖、微晶纤维素中的至少一种；所述粘合剂选自羟丙基甲基纤维素、羟丙基纤维素、羧甲基纤维素钠、中的至少一种；所述崩解剂选自羧甲淀粉钠、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠中的至少一种；所述润滑剂选自二氧化硅、硬脂酸镁、滑石粉中的至少一种；所述克拉霉素分散片还包括甜味剂，所述甜味剂选自自阿斯巴甜、糖精钠中的至少一种。CN104337778A(一种克拉霉素分散片的制备方法)公开了一种克拉霉素分散片的制备方法，其特征是：(1)按照质量比为：克拉霉素用量为100-500mg；淀粉、糊精、乳糖、微晶纤维素中的一种用量为470-870mg、羧甲淀粉钠、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠中的一种用量为5-1.5mg、二氧化硅、硬脂酸镁、滑石粉中的一种用量为5-2.5mg、阿斯巴甜、糖精钠中的一种用量为5-10mg和适量的粘合剂的比例称取原辅料；(2)将克拉霉素与部分乳糖超微粉碎成直径＜10μm的微粉，得混粉A；(3)取余下填充剂与一部分崩解剂混合组成混粉B；(4)将粘合剂与纯化水混合配制成质量分数1％-10％的水溶液；(5)将混粉B以等量递增方式与混粉A混和，放入三维混合机中混合30-40分钟，加入步骤(4)所制备的水溶液中制成软材，过16-24目筛；在50－70℃干燥，用16-24目筛整粒；(6)将余下崩解剂、润滑剂、甜味剂外加到步骤(5)所得颗粒中既得物料C；(7)将步骤(6)中所得物料C压片，既得克拉霉素分散片；所述的填充剂选自淀粉、糊精、乳糖、微晶纤维素中的至少一种；所述的粘合剂选自羟丙甲纤维素、羟丙纤维素、羧甲基纤维素钠中的至少一种；所述的崩解剂选自羧甲淀粉钠、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠中的至少一种；所述的润滑剂选自二氧化硅、硬脂酸镁、滑石粉中的至少一种；所述甜味剂选自阿斯巴甜、糖精钠中的至少一种。
发明内容
本发明的目的在于提供一种溶出度高、分散性好的克拉霉素分散片，并同时提供其生产工艺。
为实现上述目的，本发明所采取的技术方案是：一方面，本发明提供了一种克拉霉素分散片，包括如下重量配比的原料及辅料：克拉霉素250份、填充剂120～200份、崩解剂30～80份、增溶剂1～10份、助流剂5～30份以及粘合剂10～40份；
进一步的，所述填充剂选自淀粉、糊精、乳糖、微晶纤维素中的中的任意一种或几种；更进一步的，所述填充剂为微晶纤维素；
进一步的，所述崩解剂选自低取代羟丙纤维素、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠中的任意一种或几种；进一步的，所述崩解剂为低取代羟丙纤维素和交联聚乙烯吡咯烷酮；
进一步的，所述增溶剂为十二烷基硫酸钠；
进一步的，所述助流剂选自滑石粉、月桂醇硫酸镁、硬脂酸镁或二氧化硅；进一步优选的，所述助流剂选自硬脂酸镁或二氧化硅；
进一步的，所述粘合剂选自玉米淀粉、羟丙甲纤维素、羟丙纤维素、羧甲基纤维素钠中的至少一种；进一步的，所述粘合剂为玉米淀粉；
进一步的，所述克拉霉素分散片，由如下重量配比的原料及辅料：克拉霉素250份、微晶纤维素102 147.00份、低取代羟丙纤维素26.0份、交联聚维酮25.00份、十二烷基硫酸钠5.00份、硬脂酸镁5.00份、二氧化硅15.00份、玉米淀粉21.00份；
本发明的另一方面提供了一种上述克拉霉素分散片的制备方法，包括以下步骤：
S1过筛：将克拉霉素、低取代羟丙纤维素、交联聚维酮、十二烷基硫酸钠、玉米淀粉分别过80目筛，微晶纤维素102过40目筛，硬脂酸镁和微粉硅胶分别过100目筛，备用；
S2称量：按照以上重量配比称取各原料及辅料；
S2混合：S3将原辅料加入到三维运动混合机或者二维运动混合机中混合均匀，压片、即得。
有益效果
1.本发明加入增溶剂十二烷基硫酸钠可以有效克服克拉霉素难溶导致的溶出度不好的问题，并且有效保证药物含量的均匀度；
2.本发明处方中采用特定的微晶纤维素102作为辅料，制备方法不需要进行湿法制粒，只需经过混合均匀，即可进行压片，生产操作简单可控，易于操作，不仅能够有效节约成本，而且重复性高，产品质量可控。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面结合具体实施例对发明进行清楚、完整的描述。
实施例1
一种克拉霉素分散片，包括如下重量配比的原料及辅料：克拉霉素250g、微晶纤维素102 120.00g、低取代羟丙纤维素20.00g、交联聚维酮20.00g、十二烷基硫酸钠2.00g、硬脂酸镁4.00g、二氧化硅4.00g、玉米淀粉15.00g；上述克拉霉素分散片的制备方法，包括以下步骤：
S1过筛：将克拉霉素、低取代羟丙纤维素、交联聚维酮、十二烷基硫酸钠、玉米淀粉分别过80目筛，微晶纤维素102过40目筛，硬脂酸镁和微粉硅胶分别过100目筛，备用；
S2称量：按照以上重量配比称取各原料及辅料；
S2混合：S3将原辅料加入到三维运动混合机或者二维运动混合机中混合均匀，压片、即得。
实施例2
一种克拉霉素分散片，包括如下重量配比的原料及辅料：克拉霉素250g、微晶纤维素102 200.00g、低取代羟丙纤维素40.00g、交联聚维酮40.00g、十二烷基硫酸钠10.00g、硬脂酸镁15.00g、二氧化硅15.00g、玉米淀粉40.00g；上述克拉霉素分散片的制备方法，包括以下步骤：
S1过筛：将克拉霉素、低取代羟丙纤维素、交联聚维酮、十二烷基硫酸钠、玉米淀粉分别过80目筛，微晶纤维素102过40目筛，硬脂酸镁和微粉硅胶分别过100目筛，备用；
S2称量：按照以上重量配比称取各原料及辅料；
S2混合：S3将原辅料加入到三维运动混合机或者二维运动混合机中混合均匀，压片、即得。
实施例3
一种克拉霉素分散片，包括如下重量配比的原料及辅料：克拉霉素250g、微晶纤维素102 147.00g、低取代羟丙纤维素26.00g、交联聚维酮25.00g、十二烷基硫酸钠5.00g、硬脂酸镁5.00g、二氧化硅15.00g、玉米淀粉21.00g；上述克拉霉素分散片的制备方法，包括以下步骤：
S1过筛：将克拉霉素、低取代羟丙纤维素、交联聚维酮、十二烷基硫酸钠、玉米淀粉分别过80目筛，微晶纤维素102过40目筛，硬脂酸镁和微粉硅胶分别过100目筛，备用；
S2称量：按照以上重量配比称取各原料及辅料；
S2混合：S3将原辅料加入到三维运动混合机或者二维运动混合机中混合均匀，压片、即得。
对比例1
一种克拉霉素分散片，包括如下重量配比的原料及辅料：克拉霉素250g、微晶纤维素CG 147.00g、低取代羟丙纤维素26.00g、交联聚维酮25.00g、十二烷基硫酸钠5.00g、硬脂酸镁5.00g、二氧化硅15.00g、玉米淀粉21.00g；上述克拉霉素分散片的制备方法，包括以下步骤：
称量：按处方量称量备料，然后过80目筛，备用。混合制粒：按处方量将微晶纤维素CG、低取代羟丙纤维素、克拉霉素、十二烷基硫酸钠、交联聚维酮加入湿法混合制粒机，干混10分钟，加入粘合剂(约7.0％的淀粉浆，温度≤60℃)；继续搅拌3分钟，制成适宜软材后，用20目尼龙筛网制粒，干燥后过20目尼龙筛整粒。总混压片：将干颗粒加入硬脂酸镁和二氧化硅在混合机总混30分钟，检验合格后，选用
浅凹冲头，按规定片重压片。
实验例1：对实施例1-3以及对比例1得到的片剂，分别进行分散均匀性、溶出度、崩解度的检查，检查结果见表1。
表1
| 实施例 | 溶出度 | 分散均匀性 | 含量(％) |
| 实施例1 | 符合规定 | 符合规定 | 99.4 |
| 实施例2 | 符合规定 | 符合规定 | 99.8 |
| 实施例3 | 符合规定 | 符合规定 | 100.2 |
| 对比例1 | 符合规定 | 符合规定 | 99.5％ |
实验例2加速实验：
(1)将实施例3的产品进行加速实验，实验结果如表2所示(0.25g(25万单位))：
表2
(2)将对比例1的产品进行加速实验，实验结果如表3所示(0.25g(25万单位))：
表3
由此可见，实施例3制备的片剂具有良好的稳定性，随着时间的推移，含水量、分散均匀性、含量均保持稳定，有关物质含量并未增加，而对比例1获得的片剂分散均匀性、含水量、有关物质等指标有上升趋势，而产品含量则有下降趋势明显。
以上实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明实施例技术方案的精神和范围。
Claims (8)
1.一种克拉霉素分散片，其特征在于，包括如下重量配比的原料及辅料：克拉霉素250份、填充剂120～200份、崩解剂30～80份、增溶剂1～10份、助流剂5～30份以及粘合剂10～40份。
2.根据权利要求1所述的克拉霉素分散片，其特征在于，所述填充剂选自淀粉、糊精、乳糖、微晶纤维素中的中的任意一种或几种；更进一步的，所述填充剂为微晶纤维素。
3.根据权利要求1所述的克拉霉素分散片，其特征在于，所述崩解剂选自低取代羟丙纤维素、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠中的任意一种或几种；进一步的，所述崩解剂为低取代羟丙纤维素和交联聚乙烯吡咯烷酮。
4.根据权利要求1所述的克拉霉素分散片，其特征在于，所述增溶剂为十二烷基硫酸钠。
5.根据权利要求1所述的克拉霉素分散片，其特征在于，所述助流剂选自滑石粉、月桂醇硫酸镁、硬脂酸镁或二氧化硅；进一步优选的，所述助流剂选自硬脂酸镁或二氧化硅。
6.根据权利要求1所述的克拉霉素分散片，其特征在于，所述粘合剂选自玉米淀粉、羟丙甲纤维素、羟丙纤维素、羧甲基纤维素钠中的至少一种；进一步的，所述粘合剂为玉米淀粉。
7.根据权利要求1所述的克拉霉素分散片，其特征在于，所述克拉霉素分散片，由如下重量配比的原料及辅料：克拉霉素250份、微晶纤维素102 147.00份、低取代羟丙纤维素26.00份、交联聚维酮25.00份、十二烷基硫酸钠5.00份、硬脂酸镁5.00份、二氧化硅15.00份、玉米淀粉21.00份。
8.一种权利要求1～7任一项所述克拉霉素分散片的制备方法，其特征在于，包括以下步骤：
S1过筛：将克拉霉素、低取代羟丙纤维素、交联聚维酮、十二烷基硫酸钠、玉米淀粉分别过80目筛，微晶纤维素102过40目筛，硬脂酸镁和微粉硅胶分别过100目筛，备用；
S2称量：按照以上重量配比称取各原料及辅料；
S2混合：S3将原辅料加入到三维运动混合机或者二维运动混合机中混合均匀，压片、即得。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020061333A1 (en) * | 1999-03-30 | 2002-05-23 | Noel Zakarian | Dispersible macrolide compounds and method for production thereof |
| CN106265552A (zh) * | 2015-05-19 | 2017-01-04 | 成都宝科生物科技有限公司 | 一种克拉霉素分散片的制备方法 |
| CN109745294A (zh) * | 2019-03-14 | 2019-05-14 | 瑞阳制药有限公司 | 克拉霉素片及其制备方法 |
-
2022
- 2022-06-17 CN CN202210689177.1A patent/CN114948887A/zh active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020061333A1 (en) * | 1999-03-30 | 2002-05-23 | Noel Zakarian | Dispersible macrolide compounds and method for production thereof |
| CN106265552A (zh) * | 2015-05-19 | 2017-01-04 | 成都宝科生物科技有限公司 | 一种克拉霉素分散片的制备方法 |
| CN109745294A (zh) * | 2019-03-14 | 2019-05-14 | 瑞阳制药有限公司 | 克拉霉素片及其制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| 徐珍霞,吴晓松: "克拉霉素分散片的处方工艺改进", 中国药房 * |
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