Effects of Crystal Form on Solubility and Pharmacokinetics: A Crystal Engineering Case Study of Lamotrigine

2010 ◽  
Vol 10 (1) ◽  
pp. 394-405 ◽  
Author(s):  
Miranda L. Cheney ◽  
Ning Shan ◽  
Elisabeth R. Healey ◽  
Mazen Hanna ◽  
Lukasz Wojtas ◽  
...  
Keyword(s):  
Crystal Engineering ◽  
Crystal Form

scholarly journals Charge density studies on 1:1 co-crystals of ethenzamide and saccharin

2014 ◽  
Vol 70 (a1) ◽  
pp. C964-C964
Author(s):  
Lucy Mapp ◽  
Mateusz Pitak ◽  
Simon Coles ◽  
Srinivasulu Aitipamula
Keyword(s):  
Hydrogen Bonds ◽  
Charge Density ◽  
Crystal Engineering ◽  
Chemical Properties ◽  
Secondary Level ◽  
Crystal Form ◽  
Monoclinic Space Group ◽  
Stoichiometric Ratio ◽  
Distribution Analysis ◽  
Space Group

The study of multi-component crystals, as well as the phenomenon of polymorphism, both have relevance to crystal engineering. Obtaining a specific polymorph is crucial as different polymorphs usually exhibit different physical and chemical properties and often the origin of this behaviour is unknown. This is especially important in the pharmaceutical industry. Herein, we present results of comparative studies of an analgesic drug, ethenzamide and its co-crystals with saccharin. The co-crystalisation of ethenzamide (2-ethoxybenzamide, EA) with saccharin (1,1-dioxo-,1,2-benzothiazol-3-one, SAC) with a 1:1 stoichiometric ratio resulted in two polymorphic forms of the co-crystal. Form I crystallises in the triclinic P-1 space group, whereas form II crystallises in monoclinic space group P21/n. Previous crystal structure analyses on forms I and II revealed that in both polymorphs the primary carboxy-amide-imide heterosynthon is the same, however the secondary level of interactions which extends the hydrogen bond network is different. Form I consists of extended linear tapes via N-H···O hydrogen bonds, whereas form II is composed of stacks of tetrameric motifs including N-H···O hydrogen bonds and C-H···O interactions. These two forms of EA-SAC can be classified as synthon polymorphs at a secondary level of hydrogen bonding [1]. In our approach an accurate, high resolution charge density distribution analysis has been carried out to obtain greater insight into the electronic structures of both types of the EA-SAC co-crystals and relate differences in electronic distribution with their polymorphic behaviour. To describe the nature and role of inter and intra-molecular interactions in a quantitative manner, the Hansen-Coppens formalism [2] and Bader's AIM theory [3] approach have been applied.

Can crystal engineering be as beneficial as micronisation and overcome its pitfalls?: A case study with cilostazol

2015 ◽  
Vol 491 (1-2) ◽  
pp. 26-34 ◽  
Author(s):  
Kodukula Sai Gouthami ◽  
Dinesh Kumar ◽  
Rajesh Thipparaboina ◽  
Rahul B. Chavan ◽  
Nalini R. Shastri
Keyword(s):  
Crystal Engineering

Crystal engineering or crystal mysticism? A case study

CrystEngComm ◽  
2005 ◽  
Vol 7 (75) ◽  
pp. 458 ◽  
Author(s):  
Joel S. Miller
Keyword(s):  
Crystal Engineering

scholarly journals Structural analysis of biological targets by host:guest crystal lattice engineering

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Patrick Ernst ◽  
Andreas Plückthun ◽  
Peer R. E. Mittl
Keyword(s):  
Crystal Lattice ◽  
Crystal Engineering ◽  
Fluorescent Protein ◽  
Crystal Form ◽  
Host Lattice ◽  
Guest Molecules ◽  
Biological Targets ◽  
X Ray Crystallography ◽  
Green Fluorescent ◽  
Difference Fourier

Abstract To overcome the laborious identification of crystallisation conditions for protein X-ray crystallography, we developed a method where the examined protein is immobilised as a guest molecule in a universal host lattice. We applied crystal engineering to create a generic crystalline host lattice under reproducible, predefined conditions and analysed the structures of target guest molecules of different size, namely two 15-mer peptides and green fluorescent protein (sfGFP). A fusion protein with an N-terminal endo-α-N-acetylgalactosaminidase (EngBF) domain and a C-terminal designed ankyrin repeat protein (DARPin) domain establishes the crystal lattice. The target is recruited into the host lattice, always in the same crystal form, through binding to the DARPin. The target structures can be determined rapidly from difference Fourier maps, whose quality depends on the size of the target and the orientation of the DARPin.

Supramolecular Architectures of Meloxicam Carboxylic Acid Cocrystals, a Crystal Engineering Case Study

2010 ◽  
Vol 10 (10) ◽  
pp. 4401-4413 ◽  
Author(s):  
Miranda L. Cheney ◽  
David R. Weyna ◽  
Ning Shan ◽  
Mazen Hanna ◽  
Lukasz Wojtas ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Crystal Engineering ◽  
Supramolecular Architectures

scholarly journals Co-Crystal Formation of Antibiotic Nitrofurantoin Drug and Melamine Co-Former Based on a Vibrational Spectroscopic Study

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 56 ◽  
Author(s):  
Ziming Zhang ◽  
Qiang Cai ◽  
Jiadan Xue ◽  
Jianyuan Qin ◽  
Jianjun Liu ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Crystal Engineering ◽  
Molecular Hydrogen ◽  
Density Functional ◽  
Structural Changes ◽  
Structural Information ◽  
Spectroscopic Method ◽  
Crystal Form ◽  
Crystal Formation ◽  
Terahertz Time Domain Spectroscopy

The co-crystallization of active pharmaceutical ingredients (APIs) has received increasing attention due to the modulation of the relative physicochemical properties of APIs such as low solubility, weak permeability and relatively inferior oral bioavailability. Crystal engineering plays a decisive role in the systematic design and synthesis of co-crystals by means of exerting control on the inter-molecular interactions. The characterization and detection of such co-crystal formations plays an essential role in the field of pharmaceutical research and development. In this work, nitrofurantoin (NF), melamine (MELA) and their hydrated co-crystal form were characterized and analyzed by using terahertz time-domain spectroscopy (THz-TDS) and Raman vibrational spectroscopy. According to the experimental THz spectra, the hydrated co-crystal form has characteristic absorption peaks at 0.67, 1.05, 1.50 and 1.73 THz, while the THz spectra for the two raw parent materials (NF and MELA) are quite different within this spectral region. Similar observations were made from the experimental Raman vibrational spectra results. Density functional theory (DFT) calculation was performed to help determine the major vibrational modes of the hydrated co-crystal between nitrofurantoin and melamine, as well as identify the structural changes due to inter- and/or intra-molecular hydrogen bonding motifs between NF and MELA. The results of the theoretical frequency calculations corroborate the THz and Raman experimental spectra. The characteristic bands of the NF–MELA-hydrated co-crystal between nitrofurantoin and melamine were also determined based on the DFT simulated calculation. The reported results in this work provide us with a wealth of structural information and a unique vibrational spectroscopic method for characterizing the composition of specific co-crystals and inter-molecular hydrogen bonding interactions upon pharmaceutical co-crystallization.

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