CN114948889A - 一种噁拉戈利片的制备方法及其制备的噁拉戈利片 - Google Patents
一种噁拉戈利片的制备方法及其制备的噁拉戈利片 Download PDFInfo
- Publication number
- CN114948889A CN114948889A CN202210692214.4A CN202210692214A CN114948889A CN 114948889 A CN114948889 A CN 114948889A CN 202210692214 A CN202210692214 A CN 202210692214A CN 114948889 A CN114948889 A CN 114948889A
- Authority
- CN
- China
- Prior art keywords
- tablet
- particle
- granulating
- tablets
- mixing
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 238000002156 mixing Methods 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000011248 coating agent Substances 0.000 claims abstract description 14
- 238000000576 coating method Methods 0.000 claims abstract description 14
- 239000008187 granular material Substances 0.000 claims abstract description 9
- 238000007908 dry granulation Methods 0.000 claims abstract description 6
- 239000000463 material Substances 0.000 claims abstract description 5
- 239000002245 particle Substances 0.000 claims description 44
- 239000011230 binding agent Substances 0.000 claims description 18
- 239000000853 adhesive Substances 0.000 claims description 16
- 230000001070 adhesive effect Effects 0.000 claims description 16
- 239000000314 lubricant Substances 0.000 claims description 14
- 239000000843 powder Substances 0.000 claims description 10
- 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 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 238000005303 weighing Methods 0.000 claims description 9
- 239000000945 filler Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 238000007873 sieving Methods 0.000 claims description 6
- 238000007906 compression Methods 0.000 claims description 4
- 230000006835 compression Effects 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 3
- 229920000881 Modified starch Polymers 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 229940069328 povidone Drugs 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 229960003943 hypromellose Drugs 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 230000004584 weight gain Effects 0.000 claims 1
- 235000019786 weight gain Nutrition 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 13
- 239000003814 drug Substances 0.000 abstract description 10
- 238000009776 industrial production Methods 0.000 abstract description 8
- 238000005265 energy consumption Methods 0.000 abstract description 7
- 230000008901 benefit Effects 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000005469 granulation Methods 0.000 abstract 1
- 230000003179 granulation Effects 0.000 abstract 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 7
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 7
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- 230000001817 pituitary effect Effects 0.000 description 4
- 201000009273 Endometriosis Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000556 agonist Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 description 2
- DQYGXRQUFSRDCH-UQIIZPHYSA-M sodium;4-[[(1r)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-4-methyl-2,6-dioxopyrimidin-1-yl]-1-phenylethyl]amino]butanoate Chemical compound [Na+].COC1=CC=CC(C=2C(N(C[C@H](NCCCC([O-])=O)C=3C=CC=CC=3)C(=O)N(CC=3C(=CC=CC=3F)C(F)(F)F)C=2C)=O)=C1F DQYGXRQUFSRDCH-UQIIZPHYSA-M 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000005641 Adenomyosis Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 102000008238 LHRH Receptors Human genes 0.000 description 1
- 108010021290 LHRH Receptors Proteins 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000009274 endometriosis of uterus Diseases 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 239000002474 gonadorelin antagonist Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 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 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002912 waste gas Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Images
Classifications
-
- 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
- A61K9/2095—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
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- 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
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P5/04—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin for decreasing, blocking or antagonising the activity of the hypothalamic hormones
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
Abstract
一种噁拉戈利片的制备方法及其制备的噁拉戈利片,它涉及医药技术领域,本发明要解决目前噁拉戈利片的制备工艺不适于工业化生产,能耗高的问题。工艺:将原料与pH调节剂共同15Hz频率混合30min,再将颗粒内的其他辅料频率共同混合30min,经过干法制粒工艺后,颗粒与外加辅料15Hz频率共同混合30min、经过压片、包衣,最终得到噁拉戈利片制剂。其制粒工艺制备过程避免了水分和温度的引入,所制备片剂具有良好的稳定性。更重要的是其生产工艺制备的噁拉戈利片体外溶出与参比制剂相似,质量稳定。本发明具有工艺简单,适合大规模工业生产的优点。
Description
技术领域
本发明属于医药技术领域,具体涉及一种噁拉戈利片的制备方法及其制备的噁拉戈利片。
背景技术
噁拉戈利片是由艾伯维开发的口服的***释放激素(GnRH)拮抗剂,于2018年首次在美国上市,商品名为Orilissa,用于治疗子宫内膜异位相关的中度至重度疼痛。
噁拉戈利是一种GnRH受体拮抗剂,噁拉戈利通过与内源性GnRH竞争垂体细胞上的受体,快速地抑制垂体性腺轴,阻断内源性LH和FSH,从而降低激素分泌,达到治疗子宫内膜异位症的目的。与GnRH激动剂相比,GnRH拮抗剂可直接快速抑制垂体,对GnRH膜受体具有更高的亲和力,是天然GnRH的20倍,是激动剂的两倍。并且GnRH拮抗剂对垂体抑制呈可逆性,经其治疗后,腺垂体仍保持对GnRH的反应性,停药2~4天后垂体功能即可恢复。
噁拉戈利化学结构为:
艾伯维公司在中国专利CN111698992A公开了一种用于治疗子宫内膜异位症、子宫肌瘤、多囊卵巢综合症或子宫腺肌症的药物配制物。专利中未提供准确的制备工艺参数。没有给出一种能耗低、适合工业化生产的噁拉戈利片的制备方法。
CN202111361201.0一种噁拉戈利冻干片及其制备方法,专利工艺复杂,能耗高,不适合大规模工业生产,且所述片剂与参比制剂外形尺寸及服用方式并不一致,与参比制剂临床疗效的不一致性。且该专利需对原料药进行粉碎处理,因粉碎而引起粉尘污染。
发明内容
本发明的目的是提供一种能耗低、适合工业化生产的噁拉戈利片的制备方法。以解决目前噁拉戈利片的制备工艺不适于工业化生产,能耗高的问题。
本发明的一种噁拉戈利片的制备方法,它是按照以下步骤进行的:
步骤A.过筛:将pH调节剂过45目筛;
步骤B.称量:取各组分,按下述重量配比称量:
步骤C.预混:将噁拉戈利钠与颗粒内pH调节剂,采用三维混粉机15Hz频率混合30min;
步骤D.初混:加入颗粒内的填充剂、颗粒内粘合剂、颗粒内润滑剂,采用三维混粉机15Hz频率混合30min;
步骤E.制粒:将混合均匀的物料采用水平螺旋送料的干法制粒机制粒,得到符合要求的干颗粒;
步骤F.总混:将颗粒外的粘合剂、pH调节剂、润滑剂与干颗粒采用三维混粉机15Hz频率混合30min;
步骤G.压片:采用单冲压片机或旋转式压片机压片;
步骤H.包衣:采用高效包衣机进行包衣,即得噁拉戈利片;
所述步骤A中pH调节剂过筛后粒径d(50)不超过120μm,优选的d(50)不超过60μm;
所述步骤C中干法制粒机参数为:压辊转速:6~10rpm,送料速度:30rpm~70rpm,压辊间隙:0.8~1.3mm,压辊压力:30~90bar,整粒速度100~120rpm,整粒筛网0.8~1.0mm。
本发明的关键为采用干法制粒工艺,且粘合剂采用颗粒内与颗粒外的加入方式,所述粘合剂用量能够保证药物的释放速度与参比制剂一致。同时本发明所述赋形剂的用量,能够大大提高干法制粒过程中的颗粒收率,却不影响药物的崩解和溶出,药物稳定性好。
进一步地,所述步骤A中pH调节剂过筛后粒径d(50)小于120μm。
进一步地,所述步骤C中干法制粒机参数为:压辊转速:8~10rpm,送料速度:40rpm~60rpm,压辊间隙:1.0~1.3mm,压辊压力:40~60bar,整粒速度100~120rpm,整粒筛网0.8~1.0mm。
进一步地,所述步骤E制得的干颗粒重量百分比为60~85%。
进一步地,所述步骤G中压片硬度为7~12kg,脆碎度<1%。
进一步地,所述步骤H中所述的包衣中的包衣片床温度40~60℃,增重2~5%。
所制备的一种噁拉戈利片包括噁拉戈利钠或其药学上可接受的盐、粘合剂、pH调节剂及其他可接受的药用辅料。
进一步地,所述粘合剂为羟丙甲纤维素、聚维酮,淀粉、预胶化淀粉、甲基纤维素的一种或任意两种组合。
进一步地,所述的粘合剂为颗粒内粘合剂和颗粒外粘合剂;其中,颗粒内粘合剂与颗粒外粘合剂的质量比为1:0.3~1。
进一步地,颗粒内粘合剂与颗粒外粘合剂的质量比为1:0.5~0.9。
本发明包含以下有益技术效果:
i)本发明干法制粒生产工艺简单,减少粉料浪费,降低了设备和能源消耗,无废气排放,减少环境污染,适合工业化生产。
ii)本发明干法制粒工艺批间差异更容易控制,可操作性强,产能易于扩大。连续生产有保障,适合GMP生产管理。
iii)本发明的方案通过无水和无高温操作,可增加噁拉戈利的稳定性。
iv)本发明的生产工艺经过优化,工业化稳定,可产生巨大的社会效益和经济效益,适合普遍推广使用。
v)本发明实施方案可以有效保证药物的崩解和溶出,稳定性良好,与参比制剂具有体外溶出一致性,从而有效地保证了药物使用的安全性及有效性应用。
vi)本发明与CN202111361201.0一种噁拉戈利冻干片及其制备方法专利相比有工艺简单,能耗低,适合大规模工业生产的优点,且所述片剂与参比制剂外形尺寸及服用方式相同,提高了与参比制剂临床疗效的一致性。其次,本发明与《CN202111361201.0一种噁拉戈利冻干片及其制备方法专利相比无需对原料药进行粉碎处理,大大减少了因粉碎而引起的粉尘污染。
附图说明
图1为参比制剂与实施例样品在0.1N盐酸介质中的累积溶出曲线图;其中,A为参比制剂(商品名为Orilissa,生产企业为艾伯维),B为实施例1,C为实施例2,D为实施例3,E为实施例4,F为实施例5;
图2为参比制剂与实施例样品在pH4.5醋酸缓冲盐介质中的累积溶出曲线图;其中,A为参比制剂(商品名为Orilissa,生产企业为艾伯维),B为实施例1,C为实施例2,D为实施例3,E为实施例4,F为实施例5;
图3为参比制剂与实施例样品在pH6.8磷酸缓冲盐介质中的累积溶出曲线图;其中,A为参比制剂(商品名为Orilissa,生产企业为艾伯维),B为实施例1,C为实施例2,D为实施例3,E为实施例4,F为实施例5。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚明白,下面将详细叙述本发明所揭示内容的精神,任何所属技术领域技术人员在了解本发明内容的实施例后,当可由本发明内容所教示的技术,加以改变及修饰,其并不脱离本发明内容的精神与范围。
本发明的示意性实施例及其说明用于解释本发明,但并不作为对本发明的限定。
实施例1
本实施例的一种噁拉戈利片的制备方法包括:
A.过筛:将pH调节剂过45目筛。
B.称量:取各组分,按下述质量分数称量:34.5%噁拉戈利钠、37.5%填充剂,10%pH调节剂,3%赋形剂、10%颗粒内粘合剂,3%颗粒外粘合剂,1%颗粒内润滑剂,1%颗粒外润滑剂。
C.预混:将噁拉戈利钠与pH调节剂,采用三维混粉机15Hz频率混合30min;
D.初混:按处方量加入填充剂、颗粒内粘合剂、颗粒内润滑剂,采用三维混粉机15Hz频率混合30min;
E.制粒:将混合均匀的物料采用水平螺旋送料的干法制粒机制粒,干法制粒机参数为:压辊转速:6rpm,送料速度:32rpm,压辊间隙:1.0mm,压辊压力:80~90bar,整粒速度100rpm,整粒筛网0.8mm。
F.总混:将颗粒外的粘合剂、pH调节剂、润滑剂与干颗粒采用三维混粉机15Hz频率混合30min;
G.压片:采用单冲压片机或旋转式压片机压片,素片硬度9~12kg;
H.包衣:采用高效包衣机进行包衣,包衣片床温度50~55℃,包衣增重3%,即得噁拉戈利片。
实施例2
将实施例1步骤B的称量步骤替换为:34.5%噁拉戈利钠、35.5%填充剂,10%pH调节剂,3%赋形剂、10%颗粒内粘合剂,5%颗粒外粘合剂,1%颗粒内润滑剂,1%颗粒外润滑剂。其余不变。
实施例3
将实施例1步骤B的称量步骤替换为:34.5%噁拉戈利钠、33.5%填充剂,10%pH调节剂,3%赋形剂、10%颗粒内粘合剂,7%颗粒外粘合剂,1%颗粒内润滑剂,1%颗粒外润滑剂。其余不变。
实施例4
将实施例1步骤B的称量步骤替换为:34.5%噁拉戈利钠、35.5%填充剂,10%pH调节剂,3%赋形剂、8%颗粒内粘合剂,7%颗粒外粘合剂,1%颗粒内润滑剂,1%颗粒外润滑剂。其余不变。
实施例5
将实施例1步骤E中,压辊压力改为30~40bar,其余不变。
上述5组实施例的颗粒分布及溶出结果见表1~表4:
表1实施产品颗粒分布结果
表2实施产品0.1N盐酸介质的溶出结果
表3实施产品pH4.5醋酸缓冲盐介质的溶出结果
表4实施产品pH6.8磷酸缓冲盐介质的溶出结果
由图1至图3,以及表2至表4可知,实施本发明制得的噁拉戈利片在3种不同介质中均具有很好的累积溶出度,且与参比制剂溶出曲线相似(f2>50)。
Claims (10)
1.一种噁拉戈利片的制备方法,其特征在于,它是按照以下步骤进行的:
步骤A.过筛:将pH调节剂过45目筛;
步骤B.称量:取各组分,按下述重量配比称量:
步骤C.预混:将噁拉戈利钠与颗粒内pH调节剂,采用三维混粉机15Hz频率混合30min;
步骤D.初混:加入颗粒内的填充剂、颗粒内粘合剂、颗粒内润滑剂,采用三维混粉机15Hz频率混合30min;
步骤E.制粒:将混合均匀的物料采用水平螺旋送料的干法制粒机制粒,得到符合要求的干颗粒;
步骤F.总混:将颗粒外的粘合剂、pH调节剂、润滑剂与干颗粒采用三维混粉机15Hz频率混合30min;
步骤G.压片:采用单冲压片机或旋转式压片机压片;
步骤H.包衣:采用高效包衣机进行包衣,即得噁拉戈利片;
所述步骤A中pH调节剂过筛后粒径d(50)不超过120μm,优选的d(50)不超过60μm;
所述步骤C中干法制粒机参数为:压辊转速:6~10rpm,送料速度:30rpm~70rpm,压辊间隙:0.8~1.3mm,压辊压力:30~90bar,整粒速度100~120rpm,整粒筛网0.8~1.0mm。
2.根据权利要求1所述的一种噁拉戈利片的制备方法,其特征在于所述步骤A中pH调节剂过筛后粒径d(50)小于120μm。
3.根据权利要求1所述的一种噁拉戈利片的制备方法,其特征在于所述步骤C中干法制粒机参数为:压辊转速:8~10rpm,送料速度:40rpm~60rpm,压辊间隙:1.0~1.3mm,压辊压力:40~60bar,整粒速度100~120rpm,整粒筛网0.8~1.0mm。
4.根据权利要求1所述的一种噁拉戈利片的制备方法,其特征在于所述步骤E制得的干颗粒重量百分比为60~85%。
5.根据权利要求1所述的一种噁拉戈利片的制备方法,其特征在于所述步骤G中压片硬度为7~12kg,脆碎度<1%。
6.根据权利要求1所述的一种噁拉戈利片的制备方法,其特征在于所述步骤H中所述的包衣中的包衣片床温度40~60℃,增重2~5%。
7.如权利要求1所制备的一种噁拉戈利片,其特征在于所述的噁拉戈利片包括噁拉戈利钠或其药学上可接受的盐、粘合剂、pH调节剂及其他可接受的药用辅料。
8.根据权利要求7所述的一种噁拉戈利片,其特征在于所述粘合剂为羟丙甲纤维素、聚维酮,淀粉、预胶化淀粉、甲基纤维素的一种或任意两种组合。
9.根据权利要求7或8所述的一种噁拉戈利片,其特征在于所述的粘合剂为颗粒内粘合剂和颗粒外粘合剂;其中,颗粒内粘合剂与颗粒外粘合剂的质量比为1:0.3~1。
10.根据权利要求9所述的一种噁拉戈利片,其特征在于颗粒内粘合剂与颗粒外粘合剂的质量比为1:0.5~0.9。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210692214.4A CN114948889A (zh) | 2022-06-17 | 2022-06-17 | 一种噁拉戈利片的制备方法及其制备的噁拉戈利片 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210692214.4A CN114948889A (zh) | 2022-06-17 | 2022-06-17 | 一种噁拉戈利片的制备方法及其制备的噁拉戈利片 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114948889A true CN114948889A (zh) | 2022-08-30 |
Family
ID=82963776
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210692214.4A Pending CN114948889A (zh) | 2022-06-17 | 2022-06-17 | 一种噁拉戈利片的制备方法及其制备的噁拉戈利片 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114948889A (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116211704A (zh) * | 2023-03-28 | 2023-06-06 | 东莞市金美济药业有限公司 | 一种干法制粒方法及制备的艾拉戈克钠片 |
CN116459225A (zh) * | 2023-04-26 | 2023-07-21 | 东莞市金美济药业有限公司 | 一种艾拉戈克钠片及其制备工艺 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20190054027A1 (en) * | 2017-08-18 | 2019-02-21 | Abbvie Inc. | Solid Pharmaceutical Formulations for Treating Endometriosis, Uterine Fibroids, Polycystic Ovary Syndrome or Adenomyosis |
WO2020043763A1 (en) * | 2018-08-31 | 2020-03-05 | Sandoz Ag | Process for preparing elagolix formulations and dosage forms comprising the same |
CN111246850A (zh) * | 2017-08-18 | 2020-06-05 | 艾伯维公司 | 用于治疗子宫内膜异位症、子宫肌瘤、多囊卵巢综合症以及子宫腺肌症的固体药物配制物 |
CN111698992A (zh) * | 2017-08-18 | 2020-09-22 | 艾伯维公司 | 用于治疗子宫内膜异位症、子宫肌瘤、多囊卵巢综合症或子宫腺肌症的药物配制物 |
CN113384581A (zh) * | 2020-03-12 | 2021-09-14 | 成都倍特药业股份有限公司 | 一种包含***释放激素拮抗剂的药物组合物 |
WO2021180862A1 (en) * | 2020-03-12 | 2021-09-16 | Synthon B.V. | Pharmaceutical compositions comprising elagolix sodium |
US20210290550A1 (en) * | 2018-07-27 | 2021-09-23 | Sandoz Ag | Process for Preparing Rapidly or Very Rapidly Dissolving Tablets Comprising Freely Soluble API |
CN113876728A (zh) * | 2021-11-17 | 2022-01-04 | 南京唯创远医药科技有限公司 | 一种噁拉戈利冻干片及其制备方法 |
US11273128B1 (en) * | 2021-04-15 | 2022-03-15 | Sandoz Ag | Elagolix formulation |
-
2022
- 2022-06-17 CN CN202210692214.4A patent/CN114948889A/zh active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20190054027A1 (en) * | 2017-08-18 | 2019-02-21 | Abbvie Inc. | Solid Pharmaceutical Formulations for Treating Endometriosis, Uterine Fibroids, Polycystic Ovary Syndrome or Adenomyosis |
CN111246850A (zh) * | 2017-08-18 | 2020-06-05 | 艾伯维公司 | 用于治疗子宫内膜异位症、子宫肌瘤、多囊卵巢综合症以及子宫腺肌症的固体药物配制物 |
CN111698992A (zh) * | 2017-08-18 | 2020-09-22 | 艾伯维公司 | 用于治疗子宫内膜异位症、子宫肌瘤、多囊卵巢综合症或子宫腺肌症的药物配制物 |
US20210290550A1 (en) * | 2018-07-27 | 2021-09-23 | Sandoz Ag | Process for Preparing Rapidly or Very Rapidly Dissolving Tablets Comprising Freely Soluble API |
WO2020043763A1 (en) * | 2018-08-31 | 2020-03-05 | Sandoz Ag | Process for preparing elagolix formulations and dosage forms comprising the same |
CN113384581A (zh) * | 2020-03-12 | 2021-09-14 | 成都倍特药业股份有限公司 | 一种包含***释放激素拮抗剂的药物组合物 |
WO2021180862A1 (en) * | 2020-03-12 | 2021-09-16 | Synthon B.V. | Pharmaceutical compositions comprising elagolix sodium |
US11273128B1 (en) * | 2021-04-15 | 2022-03-15 | Sandoz Ag | Elagolix formulation |
CN113876728A (zh) * | 2021-11-17 | 2022-01-04 | 南京唯创远医药科技有限公司 | 一种噁拉戈利冻干片及其制备方法 |
Non-Patent Citations (1)
Title |
---|
张鉴等主编: "《中药制剂技术与设备》", 中国医药科技出版社 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116211704A (zh) * | 2023-03-28 | 2023-06-06 | 东莞市金美济药业有限公司 | 一种干法制粒方法及制备的艾拉戈克钠片 |
CN116459225A (zh) * | 2023-04-26 | 2023-07-21 | 东莞市金美济药业有限公司 | 一种艾拉戈克钠片及其制备工艺 |
CN116459225B (zh) * | 2023-04-26 | 2023-11-10 | 东莞市金美济药业有限公司 | 一种艾拉戈克钠片及其制备工艺 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN114948889A (zh) | 一种噁拉戈利片的制备方法及其制备的噁拉戈利片 | |
Inghelbrecht et al. | Reducing dust and improving granule and tablet quality in the roller compaction process | |
CA2572729A1 (en) | Extended release tablet formulation containing pramipexole or a pharmaceutically acceptable salt thereof, method for manufacturing the same and use thereof | |
IE890545L (en) | Pharmaceutical granulate | |
CN106389360A (zh) | 盐酸达泊西汀直压片及其制备方法 | |
WO2022037544A1 (zh) | 一种托伐普坦的药物固体制剂及制备方法 | |
WO2003028704A1 (en) | Extended release pharmaceutical composition containing metformin | |
WO2023108895A1 (zh) | 一种产品性能稳定的替米沙坦口服固体制剂及其制备方法 | |
CN109512789B (zh) | 一种可直接压片的高纯度粒状木糖醇及其制备方法 | |
CN113041250B (zh) | 一种缬沙坦氢***复方制剂及其制备工艺 | |
CN110237073B (zh) | 一种奥美沙坦酯氨氯地平片及其制备方法 | |
WO2023040075A1 (zh) | 一种稳定的头孢克肟片剂及其制备方法 | |
CN112641743B (zh) | 一种用于治疗高血压的复方制剂及其制备工艺 | |
CN111888477B (zh) | 一种贝达喹啉药物制剂 | |
EP2429501B1 (en) | Burst drug release compositions | |
CN113577035A (zh) | 一种阿哌沙班片及其制备方法 | |
CN114129524A (zh) | 对乙酰氨基酚片剂及其制备方法 | |
CN103202817A (zh) | 一种可直压性甘露醇颗粒的制备方法 | |
CN112603898A (zh) | 一种替米沙坦片剂及其制备方法 | |
CN113456601A (zh) | 一种坎地沙坦酯氢***复方片剂的制备方法 | |
CN111249246A (zh) | 一种左乙拉西坦缓释片剂及其制备方法 | |
JPWO2004006945A1 (ja) | 漢方エキス含有錠剤組成物およびその製造方法 | |
CN111228227A (zh) | 一种硫酸沙丁胺醇口腔崩解片剂及其制备方法 | |
CN110693884A (zh) | 一种复方制剂缬沙坦氨氯地平片及其制备方法 | |
CN111012750A (zh) | 一种对乙酰氨基酚片及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20220830 |