meloxicam:fumaric acid | 1446246-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: meloxicam:fumaric acid
• 英文别名: (E)-but-2-enedioic acid;4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1lambda6,2-benzothiazine-3-carboxamide；(E)-but-2-enedioic acid;4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
• CAS: 1446246-42-9
• 化学式: C₄H₄O₄*C₁₄H₁₃N₃O₄S₂
• 分子量: 467.48
• InChiKey: NOKHWVHYBXWWHB-WLHGVMLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.66
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  211
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  美洛昔康 、 富马酸 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 meloxicam:fumaric acid
  参考文献：
  名称：

  水杨酸，富马酸和苹果酸的美洛昔康共晶体的机械化学合成，表征和热行为

  摘要：

  使用液体辅助研磨方法，在非共甾体抗炎药美洛昔康中，在共形成物之间合成了三个共晶体：水杨酸，富马酸和苹果酸。拉曼光谱和傅立叶红外光谱（FTIR）等光谱技术通过显示NH或OH与CO基团之间氢键的证据，证实了这些化合物的形成。通过将结果与晶体学数据库进行比较，粉末X射线衍射验证了共晶体的形成。差示扫描量热法（DSC），同时热重和差示扫描量热法（TG-DSC），逸出气体分析法（TG-FTIR的EGA），DSC可见光分析法和被加热共晶体的视频用于研究热行为，分析成分，用苹果酸鉴定美洛昔康共晶体中的多晶型转变，并了解这些固体的分解现象。苹果酸化合物显示出独特的降解步骤，这通过TG-DSC数据和所形成残渣的FTIR分析证实。进行了溶解度测试：与纯药物相比，富马酸共晶显示出增强的性能，而苹果酸和水杨酸共晶显示出较慢的溶出曲线。

  DOI：

  10.1007/s10973-019-08118-7

文献信息

• In vivo studies of crystalline forms of meloxicam
  申请人：Hanna Mazen

  公开号：US20090203680A1

  公开（公告）日：2009-08-13

  The invention is directed to novel crystalline forms of meloxicam. These novel crystalline forms of meloxicam have improved bioavailability, an enhanced rate of dissolution and shorter time to C max in blood, as compared to pure meloxicam.

  本发明涉及美洛昔康的新晶体形式。这些新晶体形式的美洛昔康具有比纯美洛昔康更好的生物利用度，更快的溶解速度和更短的达到血浆Cmax的时间。
• Preparation and studies of the co-crystals of meloxicam with carboxylic acids
  作者：S. A. Myz、T. P. Shakhtshneider、N. A. Tumanov、E. V. Boldyreva

  DOI：10.1007/s11172-012-0248-6

  日期：2012.9

  Mechanical treatment with addition of some liquid, crystallization from solutions, and heating of the mixture components preliminary subjected to mechanical treatment were the methods used for the preparation of the co-crystals of 4-hydroxy-2-methyl-N-(5-methylthiazol-2-yl)-2H-1,2-benzothiazin-3-carboxamide 1,1-dioxide (meloxicam) with carboxylic acids. It was shown that preliminary mechanical treatment plays significant role for the synthesis, whereas the addition of small amounts of solvents accelerates the process. The co-crystals were obtained for 17 mixtures of meloxicam—carboxylic acid. The use of the co-crystals of meloxicam in the compositions of improved pharmaceutical forms was found promising, which was attributable to the fact that the dissolution rate and the solubility of the co-crystals of meloxicam with the carboxylic acids under study are higher than those for meloxicam itself.

  在制备 4-羟基-2-甲基-N-(5-甲基噻唑-2-基)-2H-1,2-苯并噻嗪-3-甲酰胺 1,1-二氧化物（美洛昔康）与羧酸的共晶体时，采用了添加一些液体的机械处理法、从溶液中结晶法和加热初步经过机械处理的混合物组分法。研究表明，初步机械处理对合成起着重要作用，而添加少量溶剂则可加速合成过程。17 种美洛昔康与羧酸的混合物都获得了共晶体。研究发现，美洛昔康与羧酸的共晶体的溶解速率和溶解度均高于美洛昔康本身，因此在改良药剂配方中使用美洛昔康共晶体大有可为。
• Supramolecular Architectures of Meloxicam Carboxylic Acid Cocrystals, a Crystal Engineering Case Study
  作者：Miranda L. Cheney、David R. Weyna、Ning Shan、Mazen Hanna、Lukasz Wojtas、Michael J. Zaworotko

  DOI：10.1021/cg100514g

  日期：2010.10.6

  Meloxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility and high permeability prescribed for indications of arthritis, primary dysmenorrhea, fever, and pain, in this contribution, we apply crystal engineering and the supramolecular synthon approach to prepare novel meloxicam cocrystal forms with various pharmaceutically acceptable or toxicologically qualified carboxylic acids. As a result, 19 pharmaceutical cocrystals including one cocrystal of a salt are synthesized by solid-state and solution methods. All resulting cocrystals are characterized by X-ray diffraction. infrared. and thermal analyses. In particular, crystal structures of six rneloxicam cocrystals are determined and reported, namely. meloxicam . 1-hydroxy-2-naphthoic acid cocrystal (1), meloxicam . glutaric acid cocrystal (2), meloxicam . L-malic acid cocrystal lit salt (3), meloxicam . salicylic acid cocrystal form 111 (4), meloxicam . fumaric acid cocrystal (5), and meloxicam . succinic acid cocrystal (6). The supramolecular assembly of each cocrystal is analyzed and discussed. It is observed that the meloxicam dimer is robust since this motif is observed in five out of six meloxicam cocrystal structures that have been determined. As part of the continuous development, the resulting meloxicam cocrystal forms will be further investigated to explore improved physicochemical and pharmacological properties.