http://pubs.acs.org/doi/pdfplus/10.1021/cr300162p

Deep Eutectic Solvents (DESs) and Their Applications

Within the framework of green chemistry, solvents occupy a strategic place. To be qualified as a green medium, these solvents have to meet different criteria such as availability, non-toxicity, biodegradability, recyclability, flammability, and low price among others. Up to now, the number of available green solvents are rather limited. Here we wish to discuss a new family of ionic fluids, so-called Deep Eutectic Solvents (DES), that are now rapidly emerging in the current literature. A DES is a fluid generally composed of two or three cheap and safe components that are capable of self-association, often through hydrogen bond interactions, to form a eutectic mixture with a melting point lower than that of each individual component. DESs are generally liquid at temperatures lower than 100 °C. These DESs exhibit similar physico-chemical properties to the traditionally used ionic liquids, while being much cheaper and environmentally friendlier. Owing to these remarkable advantages, DESs are now of growing interest in many fields of research. In this review, we report the major contributions of DESs in catalysis, organic synthesis, dissolution and extraction processes, electrochemistry and material chemistry. All works discussed in this review aim at demonstrating that DESs not only allow the design of eco-efficient processes but also open a straightforward access to new chemicals and materials.

Deep eutectic solvents: syntheses, properties and applications

Green technology actively seeks new solvents to replace common organic solvents that present inherent toxicity and have high volatility, leading to evaporation of volatile organic compounds to the atmosphere. Over the past two decades, ionic liquids (ILs) have gained enormous attention from the scientific community, and the number of reported articles in the literature has grown exponentially. Nevertheless, IL “greenness” is often challenged, mainly due to their poor biodegradability, biocompatibility, and sustainability. An alternative to ILs are deep eutectic solvents (DES). Deep eutectic solvents are defined as a mixture of two or more components, which may be solid or liquid and that at a particular composition present a high melting point depression becoming liquids at room temperature. When the compounds that constitute the DES are primary metabolites, namely, aminoacids, organic acids, sugars, or choline derivatives, the DES are so called natural deep eutectic solvents (NADES). NADES fully represen...

Natural Deep Eutectic Solvents – Solvents for the 21st Century

How do molecules aggregate in solution, and how do these aggregates consolidate themselves in crystals? What is the relationship between the structure of a molecule and the structure of the crystal it forms? Why do some molecules adopt more than one crystal structure? Why do some crystal structures contain solvent? How does one design a crystal structure with a specified topology of molecules, or a specified coordination of molecules and/or ions, or with a specified property? What are the relationships between crystal structures and properties for molecular crystals? These are some of the questions that are being addressed today by the crystal engineering community, a group that draws from the larger communities of organic, inorganic, and physical chemists, crystallographers, and solid state scientists. This Perspective provides a brief historical introduction to crystal engineering itself and an assessment of the importance and utility of the supramolecular synthon, which is one of the most important concepts in the practical use and implementation of crystal design. It also provides a look to the future from the viewpoint of the author, and indicates some directions in which this field might be moving.

Crystal engineering: from molecule to crystal.

A new generation of designer solvents emerged in the last decade as promising green media for multiple applications, including separation processes: the low-transition-temperature mixtures (LTTMs). They can be prepared by mixing natural high-melting-point starting materials, which form a liquid by hydrogen-bond interactions. Among them, deep-eutectic solvents (DESs) were presented as promising alternatives to conventional ionic liquids (ILs). Some limitations of ILs are overcome by LTTMs, which are cheap and easy to prepare from natural and readily available starting materials, biodegradable, and renewable.

Low-transition-temperature mixtures (LTTMs): a new generation of designer solvents.

The use of soluble cocrystals is a promising strategy for delivering poorly soluble drugs. However, precipitation of poorly soluble crystal form during dissolution hinders the successful tablet development of cocrystals. This work was aimed to understand the mechanisms for improving dissolution performance of a soluble cocrystals by using excess coformer. A highly soluble carbamazepine (CBZ) cocrystal with– glutaric acid (GLA) was studied. Impact of excess GLA on solubility and intrinsic dissolution rate (IDR) was assessed. Viscosity of GLA solutions was also measured. Solid form of powders and pellets was examined using powder X-ray diffractometry. IDRs of cocrystal and GLA mixtures in different ratios were measured to identify a suitable formulation for maintaining high dissolution rate of CBZ-GLA in an aqueous environment. IDR of CBZ-GLA in a pH 1.2 HCl solution was improved when GLA was present in the solution. Precipitation of CBZ·2H2O was eliminated when GLA concentration was ≥100 mg/mL. The improved IDR was accompanied by higher solubility of CBZ in GLA solution and increased solution viscosity. The trend in IDR profile matched well with the solubility profile normalized by solution viscosity. Mixture of cocrystal and GLA led to improved IDR in simulated intestinal fluid. The excess GLA increased the aqueous solubility of CBZ·2H2O and, thereby, reduced the propensity to precipitation of CBZ·2H2O during dissolution by lowering the degree of supersaturation. This strategy allowed development of a CBZ-GLA formulation with a significantly enhanced dissolution rate than CBZ-GLA.

Improving Dissolution Rate of Carbamazepine-Glutaric Acid Cocrystal Through Solubilization by Excess Coformer.

Enabling Tablet Product Development of 5-Fluorocytosine Through Integrated Crystal and Particle Engineering

Understanding the structural origins of diverse mechanical behaviors of organic crystals is critical for designing functional materials for a number of technological applications. To facilitate thi...

Structural Origins of Elastic and 2D Plastic Flexibility of Molecular Crystals Investigated with Two Polymorphs of Conformationally Rigid Coumarin

Cocrystals are an emerging class of crystalline materials composed of two or more different molecules in the same crystal lattice that are physically connected by non-ionic and non-covalent bonds. Formulating problematic drugs into cocrystals is a pragmatic strategy to manipulate solid state properties for new drug development and product reformulation. While research on cocrystals has been undergoing rapid growth over the past two decades, successful clinical translation of cocrystals is still limited. As the pharmaceutical properties of a cocrystal are decidedly dictated by the selection of cocrystal formers and resulting crystal structure, the present review begins with an overview of the current strategies in cocrystal design and preparation, followed by the potential applications of cocrystals in medicines. The major hurdles and missing knowledge gaps hindering the translation of pharmaceutical cocrystals into commercial reality are also mentioned. Finally, perspectives of cocrystals in alternative dosage forms other than for oral use, as well as latest topics of cocrystal research are highlighted. We believe that cocrystals play an important role in future drug discovery and development, offering a new direction for optimal drug delivery, combination therapy and personalized medicines.

Cocrystal engineering of pharmaceutical solids: therapeutic potential and challenges

Purpose. To examine the effects of salt form, i.e., different anions with a common cation (L-lysinium), on compaction properties and to identify the factors that determine the tensile strength of tablets. 
Methods. L-Lysine salts with the following anions were compressed at various pressures: acetate, monochloride, dichloride, L-aspartate, L-glutamate (dihydrate), and L-lysine (zwitterionic monohydrate). The yield strength of each salt was evaluated from the “out-of-die” Heckel plot. 
Results. At low compaction pressures, the tensile strength of the compacts increases linearly with increasing compaction pressure. Simultaneously, the compact tensile strength decreases exponentially with increasing yield strength of the salt. However, at high compaction pressures, the compact tensile strength is determined by the interparticulate bonding strength and not by the yield strength. The compact tensile strength, extrapolated to zero porosity, increases linearly with increasing melting temperature of the salts. 
Conclusions. The counterion affects the tableting properties of L-lysine salts. The tensile strength is controlled by both the yield strength and the interparticulate interaction strength with the former predominant at low compaction pressures and the latter predominant at high compaction pressures. The melting temperature of each L-lysine salt is a good indicator of the tensile strength of its compacts at zero porosity.

Changquan Calvin Sun

Papers

Improving Dissolution Rate of Carbamazepine-Glutaric Acid Cocrystal Through Solubilization by Excess Coformer.

Enabling Tablet Product Development of 5-Fluorocytosine Through Integrated Crystal and Particle Engineering

Structural Origins of Elastic and 2D Plastic Flexibility of Molecular Crystals Investigated with Two Polymorphs of Conformationally Rigid Coumarin

Cocrystal engineering of pharmaceutical solids: therapeutic potential and challenges

Compaction properties of L-lysine salts.