racemic ibuprofen-nicotinamide | 951381-63-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: racemic ibuprofen-nicotinamide
• 英文别名: ibuprofen - nicotinamide；Ibuprofen+nicotinamide；ibuprofen nicotinamide；ibuprofen-nicotinamide；2-[4-(2-Methylpropyl)phenyl]propanoic acid;pyridine-3-carboxamide
• CAS: 951381-63-8
• 化学式: C₆H₆N₂O*C₁₃H₁₈O₂
• 分子量: 328.411
• InChiKey: GORACSGPWBQUIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  布洛芬 、 烟酰胺 反应 1.0h， 生成 racemic ibuprofen-nicotinamide
  参考文献：
  名称：

  布洛芬/烟酰胺共晶体的多态性和稳定性：晶体合成方法的影响。

  摘要：

  在过去的十年中，用于共晶制备的设计策略的发展导致了许多合成共晶的方法，而没有考虑它们对共晶态的精确结构和稳定性的影响。另一方面，共晶形成的机理仍不清楚，尤其是鉴定主要导致共晶稳定性的相互作用类型。通过共研磨，缓慢溶剂蒸发和从熔体中结晶来制备S-布洛芬/烟酰胺和RS-布洛芬/烟酰胺共晶体，分析了晶体合成方法对共晶体多晶型的影响。X射线衍射和拉曼光谱实验表明，从熔体中再结晶得到的共晶的多晶型形式（形式A）与通过研磨和在溶液中缓慢蒸发制得的共晶形式（形式B）不同。结果表明，通过A型晶态的瞬态亚稳态微/纳米结构，可以观察到熔融共混过程中的等温和非等温重结晶。此外，还观察到，加热时，由于氢的微弱变化，A型转变为B型。债券网络。从熔体中以晶型A结晶，而不是通过其他方法从晶形B中结晶，是由于难以形成能量上与熔体中存在的超分子组织相距太远的困难。

  DOI：

  10.1016/j.ijpharm.2020.119454

文献信息

• METHOD AND PRODUCT
  申请人：Paradkar Anant

  公开号：US20110177136A1

  公开（公告）日：2011-07-21

  The present invention provides a method of producing a co-crystal, the method comprising the steps of providing a first substance and a second substance, wherein the first and second substances are compatible to form a co-crystal, mixing said first and second substances together, and exposing the mixture of said first and second substances to prolonged and sustained conditions of pressure and shear, sufficient to form a co-crystal of said first and second substance. The prolonged and sustained conditions of pressure and shear are preferably applied in an extrusion process. Associated compositions and uses thereof are also provided.

  本发明提供了一种生产共晶的方法，该方法包括以下步骤：提供第一物质和第二物质，其中第一和第二物质相容以形成共晶，将所述第一和第二物质混合在一起，并将所述第一和第二物质的混合物暴露在长时间和持续的压力和剪切条件下，足以形成所述第一和第二物质的共晶。长时间和持续的压力和剪切条件最好是在挤压过程中施加的。还提供了相关的组合物和用途。
• 一种通过溶剂挥发制备布洛芬-烟酰胺共晶的方法
  申请人：中国药科大学

  公开号：CN106632024A

  公开（公告）日：2017-05-10

  本发明涉及一种通过溶剂挥发制备摩尔比为1∶1的布洛芬‑烟酰胺共晶；将布洛芬与烟酰胺共同溶解于有机溶剂后，旋转蒸发或自然挥发挥干溶剂，获得布洛芬‑烟酰胺共晶。本发明制备的布洛芬‑烟酰胺共晶有效增加了布洛芬水溶性；工艺方法简便，成本低，质量易于控制，产品收率高(90％‑98％)，稳定性好，有利于工业化生产。
• Quantitative determination of activation energies in mechanochemical reactions
  作者：Franziska Fischer、Klaus-Jürgen Wenzel、Klaus Rademann、Franziska Emmerling

  DOI：10.1039/c6cp04280e

  日期：——

  investigations provided direct insight into formation pathways. However, the currently available theories do not predict temperature T as an influential factor. Here, we report the first determination of an apparent activation energy for a mechanochemical reaction. In a temperature-dependent in situ study the cocrystallisation of ibuprofen and nicotinamide was investigated as a model system. These experiments

  机械化学反应通常导致单一产品的100％收率，使纯化程序过时了。机械化学也是一种可持续且环保的方法。对这种方法的日益增长的兴趣与缺乏对机械化学反应性和选择性的机械理解形成了鲜明对比。最近的现场调查提供了对形成途径的直接见解。但是，当前可用的理论并未将温度T预测为影响因素。在这里，我们报告首次确定的机械化学反应的表观活化能。在与温度有关的原位研究将布洛芬和烟酰胺的共结晶作为模型系统。这些实验为全面了解研磨反应机理提供了关键性的一步。
• Mechanistic Study on Complexation-Induced <i>Spring and Hover</i> Dissolution Behavior of Ibuprofen-Nicotinamide Cocrystal
  作者：Yuanfeng Wei、Li Zhang、Ningning Wang、Peiya Shen、Haitao Dou、Kun Ma、Yuan Gao、Jianjun Zhang、Shuai Qian

  DOI：10.1021/acs.cgd.8b00978

  日期：2018.12.5

  Pharmaceutical cocrystal has gained increasing interest due to its ability to modify various physicochemical properties of hydrophobic drugs, especially solubility and dissolution. The temporarily generated supersaturation during the dissolution of cocrystals, usually called “spring and parachute” effect, would favor the oral absorption of poorly soluble drugs. In this study, biopharmaceutics classification system II drug ibuprofen (IBU) was cocrystallized with nicotinamide (NIC) by slow solvent evaporation. An AP-type complexation between IBU and NIC was observed by phase solubility study, and complexation phenomenon was verified by fluorescence quenching method. Reduction of solvation barrier by inserting extremely soluble NIC in the crystal lattice of IBU makes the cocrystal gain a 70-fold higher aqueous solubility than that of original crystalline IBU. A novel mathematic model, considering both the ionization of IBU and the complexation between IBU and NIC, was developed and well-fitted to experimental pH solubility of cocrystal. Surprisingly, instead of common spring and parachute, the prepared IBU-NIC cocrystal demonstrated an initially rapid dissolution followed by a constant high concentration, like a helicopter hovering in the sky, during its nonsink dissolution. Such a result is interpreted with a spring and hover model, which should be ascribed to the enhanced IBU solubility by complexation with the coformer NIC.

  药物共晶因其能够改变疏水性药物的各种物理化学性质，特别是溶解度和溶解性，而越来越受到关注。共晶溶解过程中暂时产生的过饱和现象通常被称为“弹簧和降落伞”效应，有利于难溶性药物的口服吸收。在这项研究中，通过缓慢蒸发溶剂，将生物制药分类系统II药物布洛芬（IBU）与烟酰胺（NIC）共结晶。通过相溶解度研究观察到IBU和NIC之间的AP型络合，并通过荧光淬灭法验证了络合现象。通过在IBU的晶格中插入极易溶解的NIC来降低溶解障碍，使共晶的水溶性比原始结晶IBU的水溶性提高了70倍。考虑到IBU的电离以及IBU和NIC之间的络合，开发了一种新的数学模型，该模型与共晶的实验pH溶解度非常吻合。令人惊讶的是，制备的IBU-NIC共晶在非沉降溶解过程中，表现出初始快速溶解，然后是恒定的高浓度，就像直升机在天空中盘旋一样，而不是常见的弹簧和降落伞效应。这种结果可以用弹簧和盘旋模型来解释，这应该归因于与共晶形成剂NIC的络合增强了IBU的溶解度。
• High drug loading pharmaceutical compositions
  申请人：Tung Hsien-Hsin

  公开号：US10792249B2

  公开（公告）日：2020-10-06

  A pharmaceutical composition of high drug loading comprising an active pharmaceutical ingredient (API) and pharmaceutical acceptable additives, which include glass-solution forming additive and/or eutectic-mixture forming additive, is provided. The composition is dispersed uniformly to form a hybrid solid dispersion consisting of crystalline-suspension, glass-solution and/or eutectic-mixture, where the crystalline API is uniformly distributed in the hybrid solid dispersion and exists in nano/micro particle size range. The amorphous API, when present, is uniformly distributed in the hybrid solid dispersion. The API may exist in different chemical and/or physical forms. The API is present in an amount of from more than about 50% wt/wt to about 90% wt/wt with respect to the total amount of the active pharmaceutical ingredient and the pharmaceutically acceptable glass-solution forming and/or eutectic-mixture forming additives. At least about 50% wt/wt of the API is dispersed in the crystalline-suspension and at least about 5% wt/wt of the API is dispersed in the glass-solution and/or eutectic-mixture. The pharmaceutical composition offers excellent dissolution rate, superior chemical and physical stability, and minimum drug-drug/drug-excipient incompatibility. The composition is beneficial for reducing the overall tablet/capsule size for low water-soluble drugs requiring high drug loading or dosage, including combination drugs.

  本发明提供了一种由活性药物成分（API）和药物可接受添加剂（包括玻璃溶液形成添加剂和/或共晶混合物形成添加剂）组成的高药物载量药物组合物。将组合物均匀分散，形成由结晶-悬浮液、玻璃-溶液和/或共晶-混合物组成的混合固体分散体，其中结晶原料药均匀分布在混合固体分散体中，粒径范围为纳米/微米。无定形原料药也均匀地分布在混合固体分散液中。原料药可以以不同的化学和/或物理形式存在。相对于活性药物成分和药学上可接受的玻璃溶液形成添加剂和/或共晶混合物形成添加剂的总量，API 的存在量从约 50% wt/wt 到约 90% wt/wt。至少约 50% wt/wt 的原料药分散在结晶悬浮液中，至少约 5% wt/wt 的原料药分散在玻璃溶液和/或共晶混合物中。该药物组合物具有优异的溶解速率、卓越的化学和物理稳定性，以及最低的药物/药物/药物辅料不相容性。该组合物有利于减少需要高药物载量或剂量的低水溶性药物（包括复方药物）的片剂/胶囊的总体积。