carbamazepine-saccharin cocrystal | 572916-55-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: carbamazepine-saccharin cocrystal
• 英文别名: carbamazepine saccharin；carbamazepine/saccharin (1:1 stoichiometry)；Cbz-sac II；benzo[b][1]benzazepine-11-carboxamide;1,1-dioxo-1,2-benzothiazol-3-one
• CAS: 572916-55-3
• 化学式: C₇H₅NO₃S*C₁₅H₁₂N₂O
• 分子量: 419.461
• InChiKey: MCDWDGAOWGBWKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  30
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  卡马西平 、 saccharin sodium salt 在 盐酸 作用下， 以 水 为溶剂， 反应 0.17h， 生成 carbamazepine-saccharin cocrystal
  参考文献：
  名称：

  WO2008/54609

  摘要：

  公开号：

文献信息

• Multiple-component solid phases containing at least one active pharmaceutical ingredient
  申请人：——

  公开号：US20030224006A1

  公开（公告）日：2003-12-04

  The subject invention concerns a method for identifying complementary chemical functionalities to form a desired supramolecular synthon. The subject invention also pertains to multiple-component phase compositions comprising one or more pharmaceutical entities and methods for producing such compositions.

  本发明的主题涉及一种用于识别形成所需超分子合成子的互补化学功能的方法。本发明还涉及包含一个或多个药物实体的多组分相组合物以及生产这种组合物的方法。
• Insight into the Mechanisms of Cocrystallization of Pharmaceuticals in Supercritical Solvents
  作者：Luis Padrela、Miguel A. Rodrigues、João Tiago、Sitaram P. Velaga、Henrique A. Matos、Edmundo Gomes de Azevedo

  DOI：10.1021/acs.cgd.5b00200

  日期：2015.7.1

  Carbon dioxide has been extensively used as a green solvent medium for the crystallization of active pharmaceutical ingredients (APIs) by replacing harmful organic solvents. This work explores the mechanisms underlying a novel recrystallization method—cocrystallization with supercritical solvent (CSS)—which enables APIs cocrystallization by suspending powders in pure CO2. Six well-known APIs that form cocrystals with saccharin (SAC) were processed by CSS, namely, theophylline (TPL), indomethacin (IND), carbamazepine (CBZ), caffeine (CAF), sulfamethazine (SFZ), and acetylsalicylic acid (ASA). Pure cocrystals were obtained for TPL, IND, and CBZ (with SAC) after 2 h of CSS processing. Convection was revealed to be a determining parameter for successful cocrystallization with high-yield levels. TPL–SAC was selected as a model system to study the cocrystallization kinetics in the gas, supercritical, and liquid phases under different conditions of pressure (8–20 MPa), temperature (30 to 70 °C), and convection regimes. The solubility of each substance in CO2 was measured at the selected working conditions. TPL–SAC showed a cocrystallization rate of 2.9% min–1, two times higher than that of IND–SAC, due to the higher solubility of TPL in CO2. The cocrystallization kinetics was also improved by increasing the CO2 density, showing that cocrystallization was limited by the dissolution of cocrystal formers. Overall, the CSS process has a potential for scale-up as a novel, simple, solvent-free batch process whenever the cocrystal phase is formed in the CO2 media.

  二氧化碳广泛用于作为绿色溶剂介质，替代有害有机溶剂，用于活性药物成分（API）的结晶。本研究探索了一种新型重结晶方法的机制——超临界溶剂共结晶（CSS），该方法通过将粉末悬浮在纯二氧化碳中，实现在二氧化碳中对API的共结晶。对六种与糖精（SAC）形成共结晶的著名API进行了CSS处理，分别是：茶碱（TPL）、吲哚美辛（IND）、卡马西平（CBZ）、咖啡因（CAF）、磺胺噻唑（SFZ）和乙酰水杨酸（ASA）。经过2小时的CSS处理，TPL、IND和CBZ（与SAC）获得了纯共结晶。对流被发现是高产率成功共结晶的重要参数。TPL–SAC被选为模型系统，研究在不同的压力（8–20 MPa）、温度（30到70°C）和对流条件下的气体、超临界和液相中的共结晶动力学。在所选工作条件下测量了每种物质在CO2中的溶解度。由于TPL在 中的溶解度更高，TPL–SAC的共结晶速率为每分钟2.9%，是IND–SAC的两倍。此外，通过提高 密度也改善了共结晶动力学，显示出共结晶受限于共结晶成分的溶解度。总体而言，CSS过程具备作为一种新型、简单、无溶剂批量处理方法的放大潜力，只要共结晶相在二氧化碳介质中形成。
• Engineering cocrystal thermodynamic stability and eutectic points by micellar solubilization and ionization
  作者：Neal Huang、Naír Rodríguez-Hornedo

  DOI：10.1039/c1ce05381g

  日期：——

  cocrystal components. An important feature of cocrystal solution equilibria is the existence of eutectic points involving coexistence of three phases, a liquid and two solids. The solution composition at the eutectic points is a critical parameter that defines the conditions of thermodynamic stability. Equations that describe the sensitivity of eutectic points and phase diagrams to micellar surfactants and

  药用共晶体备受关注，因为它们有可能增强弱效晶体的溶解度和生物利用度。 水可溶性药物。然而，共晶体的发展受到其在水性环境中差的热力学稳定性的限制。本文介绍的工作描述了通过胶束溶解和共晶组分的电离可微调共晶稳定性的机制。共晶溶液平衡的一个重要特征是共晶点的存在，涉及三个相（液体和两个固体）的共存。共晶点处的溶液组成是定义热力学稳定性条件的关键参数。提出了描述共晶点和相图对胶束表面活性剂和pH的敏感性的方程式。预测与以下几个方面的行为非常吻合卡马西平 水溶液中的共晶 月桂基硫酸钠。发现增加共晶组分之一的胶束增溶的量可赋予共晶更大的热力学稳定性并扩大其稳定区域。这些发现为共晶溶液的相行为提供了前所未有的控制水平，并且适用于稳定高可溶性共晶可能需要的多种添加剂和增溶机理。
• Relative Enthalpy of Formation for Co-Crystals of Small Organic Molecules
  作者：Mark A. Oliveira、Matthew L. Peterson、Roger J. Davey

  DOI：10.1021/cg101214m

  日期：2011.2.2

  HCBZ-Pbca. The differences in enthalpies between polymorphs were related to the differences in the packing of the molecules. Likewise, the heats of formation of the co-crystals were related to differences in molecular and crystal structures. The transfer enthalpies for the components were assessed and included in the enthalpy of formation calculation. The free energy of formation of CBZ:SAC calculated from

  1：1卡马西平：糖精（CBZ：SAC），庚酰胺：糖精（CYH：SAC）和10,11-二氢卡马西平：糖精（HCBZ：SAC）共晶体的形成焓和相对热焓差异的共晶形成-CBZ（P 2 1 / ç，P 1），CYH（P 2 1 / ç，P 1），并且HCBZ（P 2 1 / ç，PBCA）-were从溶液测量的焓来计算。结果表明，共晶体是焓稳定的，并且更稳定的多晶型物是CBZ- P 2 1。/ c，CYH- P 2 1 / c和HCBZ- Pbca。多晶型物之间的焓差与分子堆积的差异有关。同样，共晶体的形成热与分子和晶体结构的差异有关。评估了组分的转移焓，并将其包括在地层焓计算中。由三元CBZ-SAC-甲醇相图计算得出的CBZ：SAC形成的自由能表明，共晶是稳定的热力学形式，结晶动力学遵循结晶热力学。
• Direct production of carbamazepine–saccharin cocrystals from water/ethanol solvent mixtures by membrane-based crystallization technology
  作者：Gianluca Di Profio、Valentina Grosso、Antonella Caridi、Rocco Caliandro、Antonietta Guagliardi、Giuseppe Chita、Efrem Curcio、Enrico Drioli

  DOI：10.1039/c1ce05410d

  日期：——

  This communication reports on the possibility to achieve the direct production of either carbamazepine crystals or carbamazepine–saccharin cocrystals from water/ethanol solvent mixtures by using membrane-based crystallization technology, by choosing the opportune initial conditions.

  该通讯报告了通过选择合适的初始条件，利用膜基晶化技术从水/乙醇溶剂混合物中直接生产卡马西平晶体或卡马西平-糖精共晶体的可能性。