WO2014048380A1 - 阿戈美拉汀固体制剂的制备方法 - Google Patents

阿戈美拉汀固体制剂的制备方法 Download PDF

Info

Publication number
WO2014048380A1
WO2014048380A1 PCT/CN2013/084552 CN2013084552W WO2014048380A1 WO 2014048380 A1 WO2014048380 A1 WO 2014048380A1 CN 2013084552 W CN2013084552 W CN 2013084552W WO 2014048380 A1 WO2014048380 A1 WO 2014048380A1
Authority
WO
WIPO (PCT)
Prior art keywords
agomelatine
preparation
crospovidone
composition
starch
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.)
Ceased
Application number
PCT/CN2013/084552
Other languages
English (en)
French (fr)
Inventor
彭俊清
徐彪
曹宇
陈梁
杨专
余慧
李艳艳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhejiang Huahai Pharmaceutical Co Ltd
Original Assignee
Zhejiang Huahai Pharmaceutical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Zhejiang Huahai Pharmaceutical Co Ltd filed Critical Zhejiang Huahai Pharmaceutical Co Ltd
Priority to EP13842023.7A priority Critical patent/EP2902015B1/en
Publication of WO2014048380A1 publication Critical patent/WO2014048380A1/zh
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K9/14—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
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants

Definitions

  • the invention belongs to the technical field of medicine, and particularly relates to a preparation method of a agomelatine solid preparation. Background technique
  • Agomelatine tablets developed by Servier, France, are 25mg and are available under the trade name Valdoxan®/Thymanax®. It is mainly used for the treatment of adult depression. It was approved by the European Union in February 2009 and is the world's first melatonin receptor agonist antidepressant. Its molecular structure is as follows:
  • Agomelatine is almost insoluble in pH 2.0 hydrochloric acid solution, pH 4.5 acetate buffer, pH 6.8 phosphate buffer and water, so it is necessary to increase its dissolution in the formulation process to enhance its biology. Utilization.
  • Patent CN102218050A discloses a preparation method for preparing agomelatine tablets. It improves the dissolution by micronizing the agomelatine, and in particular, achieving a good dissolution effect by achieving a smaller particle size.
  • the use of special airflow pulverizing equipment for micronization of drugs requires cumbersome production and requires granular quality control of the drug, which reduces production efficiency. Summary of the invention
  • the invention provides a preparation method of a agomelatine solid preparation, firstly preparing agomelatine and crospovidone by a hot melt granulation technique, and then sieving the obtained composition. It is mixed with a pharmaceutically acceptable carrier, compressed or filled into capsules.
  • Cross-linked povidone is a white to milky white, finely divided, free-flowing, almost odorless, odorless or slightly odorous powder.
  • the main component is a 1-vinyl-2-pyrrolidone homopolymer.
  • Commercially available crospovidones of various sizes, such as Kollidon CL, Kollidon CL-M, Polyplasdone XL, Polyplasdone XL-10, can be selected in accordance with the present invention.
  • amorphous has better solubility than crystalline form, and formulations containing amorphous drugs tend to have a better dissolution rate than formulations containing crystalline drugs, but amorphous
  • the high energy state is often converted into a crystalline form during preparation and storage of the preparation, resulting in a decrease in the dissolution rate of the drug, which in turn affects the bioavailability of the drug.
  • agomelatine is mixed with crospovidone, heated to melt the agomelatine, and agomelatine is dispersed in a liquid form into the pores of crospovidone, and then cooled and sieved. Since agomelatine is adsorbed by crospovidone after melting, the molecular spacing increases, and amorphous form is obtained after cooling. Because of the separation of the reticular povidone network structure, agomelatine is inhibited. Crystallization, which does not change to a crystalline state during preparation and storage of the preparation, maintains the crystal form stability of the product, thereby ensuring the dissolution rate and bioavailability of the product.
  • the particles are relatively loose and can be easily sieved to obtain the agomelatine composition without the need for a pulverization step. Moreover, the composition has good fluidity, and it is convenient to carry out subsequent preparation process.
  • the present invention screens for the ratio of crospovidone to agomelatine.
  • agomelatine could not exhibit an amorphous form in the formed composition.
  • the ratio of crospovidone to agomelatine is greater than 2: 1, it can ensure that agomelatine exists in an amorphous form. At this point the drug can have better solubility properties. The solubility performance is improved relative to the crystalline drug.
  • the ratio of crospovidone to agomelatine is too high, and the prepared capsules have a large weight.
  • the weight ratio of crospovidone to agomelatine is from 2:1 to 10:1, preferably from 2:1 to 5:1. At this time, the tablet or capsule has a good quality and a relatively suitable weight.
  • agomelatine has various crystalline forms, such as Form I, its melting point is about 98 °C.
  • Form II having a melting point of about 108 V, and a crystalline form VI having a melting point of about 94 ° C. Therefore, the heating referred to in the present invention causes the melting of agomelatine to mean that the temperature of the material is higher than the melting point of agomelatine.
  • the crystal form of agomelatine it is heated to 95 ° C, 100 ° C, 120 ° C or 150 ° C.
  • the specific temperature selection needs to be set according to the crystal form of the drug. In short, it is necessary to ensure that the drug can be melted at this temperature.
  • agomelatine Since the present invention requires the drug to be melted, there is no strict requirement for the particle size of agomelatine, which is relatively simple for the preparation process, and does not require mechanical pulverization or jet pulverization of agomelatine, saving Cost and production time.
  • composition of agomelatine prepared by the present invention was placed in an environment of a temperature of 40 ⁇ 2 ° C and a relative humidity of 75 ⁇ 5% for 6 months, and an X-ray diffraction pattern showed that these compositions were placed at 6 After the month, it still exists in an amorphous state, indicating that the crystal form of the drug in the composition is stable.
  • pharmaceutically acceptable additives include diluents, binders, lubricants and the like. After the preparation of the composition, it can be tableted or filled with a capsule by mixing with the following auxiliary materials, and further prepared to obtain the above solid preparation.
  • Diluents suitable for the solid preparation of agomelatine of the present invention include: mannitol, lactose, microcrystalline cellulose, starch, Corn starch, partially pregelatinized starch, sucrose, lactose, glucose, dextrin, calcium hydrogen phosphate, calcium dihydrogen phosphate, maltitol.
  • the binder of the agomelatine solid preparation suitable for the present invention includes: hydroxypropylcellulose, povidone, copovidone, hypromellose, and the like.
  • Lubricants suitable for the solid preparation of agomelatine of the present invention include: talc, magnesium stearate, sodium stearyl fumarate, and micronized silica gel.
  • the composition of agomelatine provided by the present invention is stable in quality, the obtained solid preparation has good in vitro dissolution property, and the prepared composition is simple, clean and suitable for industrial production.
  • Figure 1 is an X-ray powder diffraction pattern of agomelatine bulk drug
  • Example 2 is an X-ray powder diffraction pattern of the composition of agomelatine prepared in Example 2;
  • Figure 3 is a composition of agomelatine prepared in Example 2 placed at 40 degrees, 75% humidity for 6 months. X-ray powder diffraction pattern. detailed description
  • Example 1 The present invention will be further described in detail below with reference to the embodiments, but is not limited to the embodiments described below. Where “%” means “% by weight”. To demonstrate the advantages of this technique, the agomelatine used in Examples 1-8 has substantially similar particle sizes. Example 1
  • the composition of the agomelatine bulk drug, the agomelatine prepared in Example 2, and the X-ray powder diffraction pattern after standing for 6 months are shown in Figures 1, 2, and 3, respectively.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

阿戈美拉汀固体制剂的制备方法
技术领域
本发明属于医药技术领域， 具体的涉及到一种阿戈美拉汀固体制剂的制备方法。 背景技术
阿戈美拉汀片 （agomelatine tablets) 由法国施维雅公司开发， 规格是 25mg， 其商品名为 维度新， 商品名 Valdoxan®/Thymanax®。 主要用于成人抑郁症的治疗， 2009年 2月获得欧盟的 上市批准， 是世界上第一个褪黑激素受体激动剂抗抑郁药。 其分子结构式如下：
Figure imgf000002_0001
阿戈美拉汀在 pH2.0的盐酸溶液， pH4.5的醋酸盐缓冲液， pH6.8的磷酸盐缓冲液和 水中几乎不溶， 因此在制剂工艺中需要提高其溶出度以增强其生物利用度。
溶解性差的药物在制剂开发中带来了技术困难，主要是低溶出度导致吸收困难或生物利 用度下降， 因此需要解决溶解性差药物的溶出问题。
专利 CN102218050A公开了一种制备阿戈美拉汀片的制备方法。其通过将阿戈美拉汀进 行微粉化以提高溶出度的效果， 特别是达到较小的颗粒度可以达到良好的溶出效果。但是对 药物进行微粉化需要专用的气流粉碎设备， 生产上比较繁琐， 需要对药物进行颗粒度的质量 控制， 这都降低了生产效率。 发明内容
本发明提供了一种阿戈美拉汀固体制剂的制备方法，首先将阿戈美拉汀与交联聚维酮通 过热熔制粒技术制备成组合物， 再将获得的组合物过筛后与药学上可接受的载体混合， 压片 或灌装成胶囊。
交联聚维酮 （PVPP) 是一种白色到乳白色、 细分散， 自由流动， 几乎无味、 无臭或稍 有气味的粉末， 主要成分为 1-乙烯基 -2-吡咯烷酮均聚物。 根据本发明可选择市售的不同规 格的交联聚维酮， 例如 Kollidon CL, Kollidon CL-M, Polyplasdone XL, Polyplasdone XL- 10 的交联聚维酮。 对于同一种药物， 一般而言， 无定形比结晶型具有更好的溶解性， 相对于含有结晶型 药物的制剂而言，含有无定形药物的制剂往往具有更好的溶出速率，但是无定形属于高能态， 往往会在制剂制备和储存过程中转化为结晶型， 导致药物溶出速率降低， 进而影响药物的生 物利用度。
本发明将阿戈美拉汀与交联聚维酮混合， 加热使阿戈美拉汀熔融， 阿戈美拉汀以液态 形式分散到交联聚维酮孔隙中， 再冷却、 过筛。 由于阿戈美拉汀熔融后被交联聚维酮吸附， 分子间距增大， 冷却后得到无定形物， 又因为交联聚维酮网状分子结构的分隔作用， 抑制了 阿戈美拉汀结晶， 在制剂制备和储存过程中不会转变为结晶态， 保持了产品的晶型稳定， 进 而确保产品的溶出速率和生物利用度。
阿戈美拉汀与交联聚维酮经过热熔造粒后， 颗粒较为松散， 能轻松的过筛得到阿戈美 拉汀组合物， 不需要进行粉碎步骤。 且组合物流动性较好， 比较方便的进行后续的制剂工艺 处理。
本发明筛选了交联聚维酮与阿戈美拉汀的比例。 发现交联聚维酮用量太少时， 形成的 组合物中， 阿戈美拉汀无法呈现无定形态。 当交联聚维酮与阿戈美拉汀的比例大于 2: 1的时 候， 能保证阿戈美拉汀以无定形态存在。 此时药物能有较好的溶解性能。 相对于结晶药物而 言， 溶解性能有所提升。 而交联聚维酮与阿戈美拉汀比例过高， 制备的片子胶囊重量较大。 因此根据本发明， 交联聚维酮与阿戈美拉汀的重量比为 2: 1至 10: 1， 优选 2: 1至 5: 1。此时片 剂或胶囊具有较好的质量和较为合适的重量。
由于阿戈美拉汀有多种结晶形式， 比如晶型 I， 其熔点约 98°C。 晶型 II， 其熔点约 108 V , 晶型 VI， 其熔点约 94°C， 因此本发明所指加热使阿戈美拉汀熔融是指加热使物料温度 高于阿戈美拉汀的熔点， 例如根据阿戈美拉汀的晶型， 加热到 95°C， 100°C， 120°C或 150 °C。 具体温度选择需根据药物晶型不同而设定， 总之需保证药物能在此温度下熔融。
因为本发明是需要将药物进行熔融， 因此对于阿戈美拉汀的颗粒度没有严格要求， 这 对于制剂的工艺来说， 相对简单， 无需对阿戈美拉汀进行机械粉碎或气流粉碎， 节约了成本 和生产时间。
将本发明制备的阿戈美拉汀的组合物，在温度 40±2°C，相对湿度为 75 ± 5%的环境中， 放置 6个月， X射线衍射图谱表明， 这些组合物在放置 6月后， 依然以无定形状态存在， 说 明组合物中药物的晶型稳定。
根据本发明， 药学上可接受的添加剂包括稀释剂、 粘合剂、 润滑剂等。 制备组合物后， 再与下述辅料进行混合即可进行压片或灌装胶囊， 进一步制备即得上述固体制剂。
适合本发明的阿戈美拉汀固体制剂的稀释剂包括： 甘露醇、 乳糖、 微晶纤维素、 淀粉、 玉米淀粉、 部分预胶化淀粉、 蔗糖、 乳糖、 葡萄糖、 糊精、 磷酸氢钙、 磷酸二氢钙、 麦芽糖 醇。
适合本发明的阿戈美拉汀固体制剂的粘合剂包括： 羟丙基纤维素， 聚维酮， 共聚维酮， 羟丙甲纤维素等。
适合本发明的阿戈美拉汀固体制剂的润滑剂包括： 滑石粉、 硬脂酸镁、 硬脂富马酸钠、 微粉硅胶。
本发明提供的阿戈美拉汀的组合物质量稳定， 所得到固体制剂具有良好体外溶出性能， 并且制备的组合物的方法简单， 清洁， 适合工业化生产。 附图说明：
图 1为阿戈美拉汀原料药的 X-射线粉末衍射图谱；
图 2为实施例 2制备的阿戈美拉汀的组合物的 X-射线粉末衍射图谱；
图 3是实施例 2制备的阿戈美拉汀的组合物在 40度， 75%湿度下放置 6月。 的 X-射线 粉末衍射图谱。 具体实施方式
下面结合实施例对本发明作进一步的详细说明，但并不局限于下述的实施例。其中"％" 是指"重量％"。为证明该技术的优点，实施例 1-8所用的阿戈美拉汀具有基本相似的颗粒度。 实施例 1
阿戈美拉汀的组合物的制备：
称取晶型 II的阿戈美拉汀 10g和 20g交联聚维酮 （型号 Kollidon CL) 混合均匀后加入 至 IJ 160 °C烘箱中 10分钟， 取出过筛冷却即可。 实施例 2
阿戈美拉汀的组合物的制备：
称取晶型 VI的阿戈美拉汀 100g和 300g交联聚维酮（型号 Kollidon CL-M)加入到带夹 套的造粒机中进行造粒， 温度设为 105°C， 搅拌 5分钟， 取出过筛冷却即可。 实施例 3
阿戈美拉汀的组合物的制备: 称取晶型 II的阿戈美拉汀 10g和 40g交联聚维酮 （型号 Polyplasdone XL) 混合均匀后 加入到 140°C烘箱中 10分钟， 取出过筛冷却即可。 实施例 4
阿戈美拉汀的组合物的制备：
称取晶型 I的阿戈美拉汀 50g和 250g交联聚维酮（型号 Polyplasdone XL-10 )加入到带 夹套的造粒机中进行造粒， 温度设为 105 °C， 搅拌 5分钟， 取出过筛冷却即可。 实施例 5
阿戈美拉汀的组合物的制备：
称取晶型 I的阿戈美拉汀 10g和 100g交联聚维酮 （型号 Kollidon CL) 混合均匀后加入 至 IJ 160 °C烘箱中 10分钟， 取出过筛冷却即可。 实施例 6
阿戈美拉汀片和胶囊的制备， 处方如下：
Figure imgf000005_0001
阿戈美拉汀片 /胶囊的制备工艺： 称取阿戈美拉汀和交联聚维酮混合均匀后加入到烘箱 中 10分钟或将阿戈美拉汀和交联聚维酮放入带夹套的造粒机进行热熔造粒， 取出过筛冷却 后与处方中余下辅料混合后压片或灌装胶囊 （处方 1， 2， 3压片， 处方 4， 5灌装胶囊） 。 对比实施例 7
将处方 1的物料按照处方比例直接混合， 压片。 对比实施例 8
将处方 5的物料按照处方比例直接混合， 灌装胶囊。 实施例 9
固体制剂溶出度实验：
片剂和胶囊， 在 pH=2.0溶出介质， 转速 50rpm， 桨法， 1000ml条件下测定溶出曲线， 结果如下：
Figure imgf000006_0001
实施例 10
阿戈美拉汀组合物晶型稳定性考察
检测阿戈美拉汀原料药、 实施例 2制备的阿戈美拉汀的组合物， 及放置 6个月后的 X- 射线粉末衍射图谱， 分别如附图 1、 2、 3所示。

Claims

权 利 要 求
1. 一种阿戈美拉汀固体制剂的制备方法， 包含如下步骤：
a. 将阿戈美拉汀和交联聚维酮混合， 得到混合物 a;
b. 将混合物 a加热， 使阿戈美拉汀熔融， 再冷却得到组合物 b;
c. 将组合物 b与药学上可接受的载体混合得到混颗粒 c;
d. 将混颗粒 c压制成片或灌装成胶囊。
2. 根据权利要求 1所述的制备方法， 其特征在于交联聚维酮与阿戈美拉汀的重量比为 2: 1 至 10: 1。
3. 根据权利要求 2所述的制备方法， 其特征在于交联聚维酮与阿戈美拉汀的重量比为 2: 1 至 5: 1。
4. 根据权利要求 1所述的制备方法，其特征在于药学上可接受的载体包括稀释剂、崩解剂、 粘合剂、 润滑剂， 其中稀释剂选自甘露醇、 乳糖、 微晶纤维素、 淀粉、 玉米淀粉、 部分 预胶化淀粉、 蔗糖、 乳糖、 葡萄糖、 糊精、 磷酸氢钙、 磷酸二氢钙、 麦芽糖醇； 粘合剂 选自羟丙基纤维素， 聚维酮， 共聚维酮， 羟丙甲纤维素； 润滑剂选自滑石粉、硬脂酸镁、 硬脂富马酸钠、 微粉硅胶。
5. 根据权利要求 1所述的制备方法， 其特征在于步骤 b加热熔融制粒的工艺采用烘箱或带 夹套的高剪切混合制粒机实现。
PCT/CN2013/084552 2012-09-28 2013-09-28 阿戈美拉汀固体制剂的制备方法 Ceased WO2014048380A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13842023.7A EP2902015B1 (en) 2012-09-28 2013-09-28 Preparation method of agomelatine solid preparation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201210381283.X 2012-09-28
CN201210381283.XA CN102988315B (zh) 2012-09-28 2012-09-28 阿戈美拉汀固体制剂的制备方法

Publications (1)

Publication Number Publication Date
WO2014048380A1 true WO2014048380A1 (zh) 2014-04-03

Family

ID=47917748

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2013/084552 Ceased WO2014048380A1 (zh) 2012-09-28 2013-09-28 阿戈美拉汀固体制剂的制备方法

Country Status (3)

Country Link
EP (1) EP2902015B1 (zh)
CN (1) CN102988315B (zh)
WO (1) WO2014048380A1 (zh)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102988315B (zh) * 2012-09-28 2017-11-17 浙江华海药业股份有限公司 阿戈美拉汀固体制剂的制备方法
CN104163771A (zh) * 2013-05-20 2014-11-26 杭州领业医药科技有限公司 阿戈美拉汀晶型ⅰ的制备方法
CN103655499B (zh) * 2013-12-23 2015-07-22 天津泰普药品科技发展有限公司 一种稳定的晶x型阿戈美拉汀片剂及其制备方法
CN103690499B (zh) * 2013-12-23 2015-05-06 天津泰普药品科技发展有限公司 一种稳定的晶i型阿戈美拉汀片剂及其制备方法
CN103816129B (zh) * 2014-02-27 2020-04-28 浙江华海药业股份有限公司 阿戈美拉汀口崩片

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102218050A (zh) 2011-06-24 2011-10-19 北京美迪康信医药科技有限公司 一种治疗抑郁症的药物组合物
CN102670514A (zh) * 2012-04-29 2012-09-19 浙江华海药业股份有限公司 阿戈美拉汀固体制剂
CN102988315A (zh) * 2012-09-28 2013-03-27 浙江华海药业股份有限公司 阿戈美拉汀固体制剂的制备方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2834890B1 (fr) * 2002-01-23 2004-02-27 Servier Lab Composition pharmaceutique orodispersible d'agomelatine
FR2923482B1 (fr) * 2007-11-09 2010-01-29 Servier Lab Nouvelle forme cristalline vi de l'agomelatine, son procede de preparation et les compositions pharmaceutiques qui la contiennent
CN102716493B (zh) * 2011-03-31 2014-05-28 天津药物研究院 含无定型态阿戈美拉汀的共聚物、其制备方法、其药物组合物及用途
CN102552211B (zh) * 2012-02-16 2013-07-17 福建广生堂药业股份有限公司 一种阿戈美拉汀的制剂组合物及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102218050A (zh) 2011-06-24 2011-10-19 北京美迪康信医药科技有限公司 一种治疗抑郁症的药物组合物
CN102670514A (zh) * 2012-04-29 2012-09-19 浙江华海药业股份有限公司 阿戈美拉汀固体制剂
CN102988315A (zh) * 2012-09-28 2013-03-27 浙江华海药业股份有限公司 阿戈美拉汀固体制剂的制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
REN, XINGFA: "Preparation of Azithromycin Solid Dispersion", CNKI CHINA MASTER'S S THESES FULL-TEXT DATABASE, 30 April 2009 (2009-04-30), pages 10, XP008175334 *

Also Published As

Publication number Publication date
CN102988315A (zh) 2013-03-27
CN102988315B (zh) 2017-11-17
EP2902015A1 (en) 2015-08-05
EP2902015A4 (en) 2016-03-09
EP2902015B1 (en) 2019-12-04

Similar Documents

Publication Publication Date Title
JP5714492B2 (ja) 粒状体、それらの調製方法、およびそれらを含む医薬品
WO2022100641A1 (zh) 包含egfr抑制剂的药物组合物及其制备方法
TW202112369A (zh) 口服膠囊劑及其製備方法
CN102670514B (zh) 阿戈美拉汀固体制剂
WO2011160541A1 (zh) 托伐普坦固体分散体及其制备方法
US20060093668A1 (en) Melt granulated composition and modified release dosage form prepared from said composition
EP2902015B1 (en) Preparation method of agomelatine solid preparation
TW570798B (en) Pharmaceutical compositions
CN110123770A (zh) 一种阿哌沙班药物组合物及其制备方法
JP6522619B2 (ja) 医薬剤形
CN104706640B (zh) 一种含有厄贝沙坦的药用组合物及其制备工艺
CN117771248A (zh) 一种依折麦布瑞舒伐他汀钙制剂及其制备方法
CN114146089B (zh) 含依非韦伦、替诺福韦和恩曲他滨的药物组合物
CN115671073B (zh) 一种熊去氧胆酸胶囊及其制备方法
CN115919793A (zh) 一种奥利司他胶囊制剂及其制备方法
AU2009337766A1 (en) Pharmaceutical formulation of nanonised fenofibrate
CN101340896A (zh) 含有低溶解性药物的压缩的固体剂型和其制备方法
CN106880598B (zh) 一种依折麦布片剂
CN104994842B (zh) 高剂量柠檬酸钾蜡基质缓释片剂
JPH10287561A (ja) イブプロフェン配合固形製剤及びその製造方法
JP2004277431A (ja) 粒状製剤及びその製造法
WO2022004871A1 (ja) 錠剤およびその製造方法
CN111803464A (zh) 一种塞来昔布胶囊制剂
CN106580924B (zh) 一种马来酸氨氯地平的多单元释放药物组合物及其制备方法
CN104523683A (zh) 一种盐酸可乐定干混悬剂及其制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13842023

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2013842023

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE