Modeling of the Aqueous Solubility of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a] pyrazine-3-carboxamide: From Micronization to Creation of Amorphous-Crystalline Composites with a Polymer.

N-butyl-N-methyl-1-phenylpyrrole[1,2-a] pyrazine-3-carboxamide (GML-3) is a potential candidate for combination drug therapy due to its anxiolytic and antidepressant activity. The anxiolytic activity of GML-3 is comparable to diazepam. The antidepressant activity of GML-3 is comparable to amitriptyline. GML-3 is an 18 kDa mitochondrial translocator protein (TSPO) ligand and is devoid of most of the side effects of diazepam, which makes the research on the creation of drugs based on it promising. However, its low water solubility and tendency to agglomerate prevented its release. This research aimed to study the effect of dry grinding, the rapid expansion of a supercritical solution (RESS), and the eutectic mixture (composite) of GML-3 with polyvinylpyrrolidone (PVP) on the particle size, dissolution rate, and lattice retention of GML-3. The use of supercritical CO2 in the RESS method was promising in terms of particle size reduction, resulting in a reduction in the particle size of GML-3 to 20-40 nm with a 430-fold increase in dissolution rate. However, in addition to particle size reduction after RESS, GML-3 began to show signs of a polymorphism phenomenon, which was also studied in this article. It was found that coarse grinding reduced particle size by a factor of 2 but did not significantly affect solubility or crystal structure. Co-milling with the polymer made it possible to level the effect of the appearance of a residual electrostatic charge on the particles, as in the case of grinding, and the increased solubility in the resulting mechanical mixtures of GML-3 with the polymer may also indicate the dissolving properties of polymers (an increase in 400-800 times). The best result in terms of GML-3 solubility was demonstrated by the resulting GML-3:PVP composite at a ratio of 1:4, which made it possible to achieve a solubility of about 80% active pharmaceutical ingredient (API) within an hour with an increase in the dissolution rate by 1600 times. Thus, the creation of composites is the most effective method for improving the solubility of GML-3, superior to micronization.

Viscosity Measurement of CO2-Solvent Mixtures for the Study of the Morphology and Size of Crystalline Particles Obtained Using Supercritical Antisolvent Precipitation.

The viscosity values of CO2-dimethylphormamide, chloroform, methanol, isopropanol, ethyl acetate, acetone, and dimethyl sulfoxide mixtures were measured at a pressure of 150 bar and a temperature of 313 K. The correlation of the mean size of levofloxacin hydrochloride and malonic acid particles precipitated using the SAS method with the viscosity of the used CO2-solvent mixtures is shown. The high viscosity of the mixtures leads to slower mixing of the solution and the antisolvent. Therefore, crystallization occurs at large fractions of the solvent, and as a consequence at a lower supersaturation. This causes the formation of larger particles when using more viscous solvents in SAS.

Supercritical fluid-assisted modification combined with the resynthesis of SmCoO3 as an effective tool to enhance the long-term performance of SmCoO3-derived catalysts for the dry reforming of methane to syngas.

The dry reforming of methane to syngas (DRM) is of increasing significance concerning, first, the production of raw materials for commercial organic/petrochemical syntheses and for hydrogen energetic, and, second, the utilization of two most harmful greenhouse gases. Herein, new SmCoO3-based DRM catalysts derived from heterometallic precursors and operated without preliminary reduction are reported. For the first time, the effect of supercritical fluids-assisted modification of the SmCoO3-derived catalysts combined with the re-oxidation of spent catalysts to SmCoO3 onto its long-term performance was studied. In particular, the modification of heterometallic precursors by supercritical antisolvent precipitation (SAS) considerably decreases coke formation upon the exploitation of the derived SmCoO3 sample. Moreover, the re-oxidation of the corresponding spent catalysts followed by pre-heating under N2 affords catalysts that stably provide syngas yields of 88-95% for at least 41 h at 900 °C. The achieved yields are among the highest ones currently reported for DRM catalysts derived from both LnMO3 perovskites and related oxides. The origins of such good performance are discussed. Given the simplicity and availability of all the applied methods and chemicals, this result opens prospects for exploiting SAS in the design of efficient DRM catalysts.

Multifunctional Elastic Nanocomposites with Extremely Low Concentrations of Single-Walled Carbon Nanotubes.

Stretchable and flexible electronics has attracted broad attention over the last years. Nanocomposites based on elastomers and carbon nanotubes are a promising material for soft electronic applications. Despite the fact that single-walled carbon nanotube (SWCNT) based nanocomposites often demonstrate superior properties, the vast majority of the studies were devoted to those based on multiwalled carbon nanotubes (MWCNTs) mainly because of their higher availability and easier processing procedures. Moreover, high weight concentrations of MWCNTs are often required for high performance of the nanocomposites in electronic applications. Inspired by the recent drop in the SWCNT price, we have focused on fabrication of elastic nanocomposites with very low concentrations of SWCNTs to reduce the cost of nanocomposites further. In this work, we use a fast method of coagulation (antisolvent) precipitation to fabricate elastic composites based on thermoplastic polyurethane (TPU) and SWCNTs with a homogeneous distribution of SWCNTs in bulk TPU. Applicability of the approach is confirmed by extra low percolation threshold of 0.006 wt % and, as a consequence, by the state-of-the-art performance of fabricated elastic nanocomposites at very low SWCNT concentrations for strain sensing (gauge factor of 82 at 0.05 wt %) and EMI shielding (efficiency of 30 dB mm-1 at 0.01 wt %).

Formation of Polymer-Carbon Nanotube Composites by Two-Step Supercritical Fluid Treatment.

An approach for polymer-carbon nanotube (CNT) composite preparation is proposed based on a two-step supercritical fluid treatment. The first step, rapid expansion of a suspension (RESS) of CNTs in supercritical carbon dioxide, is used to de-bundle CNTs in order to simplify their mixing with polymer in solution. The ability of RESS pre-treatment to de-bundle CNTs and to cause significant bulk volume expansion is demonstrated. The second step is the formation of polymer-CNT composite from solution via supercritical antisolvent (SAS) precipitation. SAS treatment allows avoiding CNT agglomeration during transition from a solution into solid state due to the high speed of phase transition. The combination of these two supercritical fluid methods allowed obtaining a polycarbonate-multiwalled carbon nanotube composite with tensile strength two times higher compared to the initial polymer and enhanced elasticity.

Modification of Poly(4-methyl-2-pentyne) in the Supercritical Fluid Medium for Selective Membrane Separation of CO2 from Various Gas Mixtures.

The modification of highly permeable films of brominated 1,2-disubstituted polyacetylene, poly(4-methyl-2-penthyne), via incorporation of in situ formed butylimidazolium bromide is reported for the first time. Principal possibility and efficiency of supercritical CO2 and CHF3 use as reaction media for the corresponding process, namely for quaternization of butylimidazole by brominated polymer are revealed. As a result, we prepared new membrane materials possessing promising properties such as stability toward organic solvents, good mechanical properties and significantly improved CO2-selectivity while maintaining gas permeability at high values. Comparative analysis of the results allowed us to determine content and conditions for the incorporation of butylimidazolium groups optimal for most efficient separation of CO2 from industrial gas mixtures. These results are of interest for the designing of new CO2 selective membranes.

Study of Dispersions of Carbon Nanotubes Modified by the Method of Rapid Expansion of Supercritical Suspensions.

The effectiveness of carbon nanotubes (CNT) deagglomeration by rapid expansion of supercritical suspensions (RESS) in nitrogen and carbon dioxide fluids was studied in this work. Two different mechanisms of deagglomeration were proposed for these two fluids at various temperature and pressure conditions. Ultrasound attenuation spectroscopy was applied as an express method of determining median diameter and aspect ratio of CNTs. At least twofold reduction of the diameter was shown for CNT bundles processed by RESS technique. Aspect ratio of processed CNTs, calculated from acoustic attenuation spectra, increased to 340. These results were in a good agreement with atomic force microscopy data.