O. I. Pokrovskiy

Preparation of hydroxypropylmethylcellulose microparticles using supercritical antisolvent precipitation

Micronization of hydroxypropylmethylcellulose using supercritical antisolvent (SAS) method is studied. The influence of various parameters, such as solvent type, polymer concentration, pressure, solution to supercritical CO2 flow rate ratio on morphology of particles is discussed. The possibility of obtaining spherical or elliptical shape hydroxypropylmethylcellulose particles of submicron size (190–620 nm) that depends on the process parameters is demonstrated.

A case of Z/E-isomers elution order inversion caused by cosolvent percentage change in supercritical fluid chromatography.

A case of elution order inversion caused by cosolvent percentage change in supercritical fluid chromatography was observed and investigated in some detail. Z- and E-isomers of phenylisobutylketone oxime experience an elution order reversal on most columns if the mobile phase consists of CO2 and alcohol. At lower percentages of alcohol Z-oxime is retained less, somewhere at 2-5% coelution occurs and at larger cosolvent volume elution order reverses - Z-oxime is eluted later than E-oxime. We suppose inversion with CO2-ROH phases happens due to a shift in balance between two main interactions governing retention. At low ROH percentages stationary phase surface is only slightly covered by ROH molecules so oximes primarily interact with adsorption sites via hydrogen bond formation. Due to intramolecular sterical hindrance Z-oxime is less able to form hydrogen bonds and consequently is eluted first. At higher percentages alcohols occupy most of strong hydrogen bonding sites on silica surface thus leaving non-specific electrostatic interactions predominantly responsible for Z/E selectivity. Z-oxime has a much larger dipole moment than E-oxime and at these conditions it is eluted later. Additional experimental data with CO2-CH3CN, hexane-iPrOH and CHF3-ROH mobile phases supporting this explanation are presented.

Effect of solvent type and concentration on size and morphology of arbidol microparticles obtained by supercritical antisolvent precipitation

The capability of arbidol microparticle preparation by supercritical antisolvent (SAS) precipitation was demonstrated. A nonmonotonic dependence of the average particle size on the concentration was found, while the position of the minimum is dependent on the type of solvent used. It is possible to prepare Arbidol particles of various morphology and size from several microns to several hundred microns depending on the conditions.

Determination of natural aromatic acids using supercritical fluid chromatography

Derivatives of benzoic and cinnamic acids are secondary metabolites of plants, widely distributed in nature and possessing biological activity. Supercritical fluid chromatography (SFC) is shown to provide a high performance separation of nine most important representatives of this class of compounds with selectivity, dramatically different from the reversed-phase high-performance liquid chromatography. The retention and chromatographic separation parameters of analytes for four stationary phases of different nature are compared and the effect of supercritical fluid parameters and the composition of the mobile phase onto the chromatographic separation are analyzed. The optimal separation is found to be achieved when using a silica-based sorbent with 2-ethylpyridinium linked groups. The proposed approach for determination of the above-mentioned compounds is based on the combination of chromatographic separation with multiwavelength spectrophotometric detection and provides the detection limits in the range of 13.0–51.3 μg/L and the analysis duration about 2.5 min. The approach is successfully tested on real objects, such as different kinds of wine.

Luminescent characteristics of Vicia faba L. bean leaves treated with SCF extracts of Reynoutria sachalinensis

The effect of supercritical fluid (SCF) extracts of giant knotweed (Reynoutria sachalinensis) on the photosynthetic activity of Vicia faba L. bean leaves was studied by the slow fluorescence induction (SFI) and thermoluminescence (TL) methods. The treatment of plants enhanced their photosynthetic activity. The maximum stimulating effect was observed for an extract prepared using carbon dioxide containing 2% ethanol as a cosolvent. The observed stimulating effect is believed to be associated with an increase in the number of electron carries in the photosynthetic electron transport chain of plant leaves due to the flux of quinonic compounds into plant cells.

Modification of Poly(4-Methyl-2-Pentyne) in Supercritical Fluid Medium for Production of CO2-Selective Gas-Separation Membranes

The work is devoted to exploring the possibility of using supercritical fluids as media for modification of polymers offering promise for production of gas-separation membranes with the goal to improve selectivity towards CO2. The possibility is demonstrated for introduction of fragments of quaternary ammonium salts into the structure of poly(4-methyl-2-pentyne) with the help of a two-stage process: bromination of the initial polymer with N-bromosuccinimide followed by the addition of the tertiary amine—N-butylimidazol— conducted in supercritical fluids as a medium. The use of trifluoromethane as the reaction medium provides the highest degree of modification of the brominated polymer with the amine. The polymer produced under the optimized conditions demonstrates a threefold increase of the calculated selectivity of separation of CO2 and N2 in comparison with the initial poly(4-methyl-2-pentyne).

Polymorphism of Risperidone in Supercritical Fluid Processes of Micronization and Encapsulation into Aliphatic Polyesters

The specific features of the transformation of risperidone polymorphs as a result of micronization and encapsulation into aliphatic polyesters (polylactides and polylactoglycolide) have been studied using supercritical (SC) carbon dioxide. It has been shown that the micronization of risperidone, which originally is polymorph A, via the rapid expansion of supercritical solutions (RESS) and the supercritical antisolvent (SAS) precipitation leads to its crystallization in less thermodynamically stable polymorph B. This transition is complete for SAS and only partial for RESS. When these micronized samples are encapsulated into polylactides and polylactoglycolides via the formation of particles from gas-saturated solutions (PGSS) and monolithization with further cryogrinding (MCG), risperidone polymorph B is partially converted back into polymorph A. At the same time, the micronization of initial risperidone polymorph A via cryogrinding and its further PGSS and MCG encapsulation into polylactides or polylactoglycolides does not result in any change in the polymorphic state of risperidone, and it always remains in initial polymorph A.

Moxifloxacin Micronization via Supercritical Antisolvent Precipitation

Supercritical antisolvent (SAS) precipitation is employed for micronization of moxifloxacin (MF), an antibiotic from the fluoroquinolone group, to develop new dosage forms of MF. With this technique, we produced, in a controllable fashion, MF particles with different sizes (0.6–8.0 μm) and morphologies (from polygonal sheets to elongated rectangular prisms). The infrared and circular dichroism spectroscopy data suggest that micronization of MF via SAS does not alter its chemical structure or cause racemization. We demonstrate that micronized forms of MF drug substance exhibit a 20 to 30% increase in the dissolution rate, as compared to the initial MF form, in a physiological medium (pH 7.4). The dissolution rate of the microparticles obtained via SAS micronization depends on their size, morphology, and degree of crystallinity. The various data obtained in this study will be used in formulating new dosage forms of MF for treatment of drug-resistant forms of tuberculoses.

A case of non-monotonous influence of pressure on enantioselectivity in supercritical fluid chromatography

Abstractnon-monotonous dependence of selectivity coefficient on pressure in the enantioseparation of salbutamol sulfate by supercritical fluid chromatography was discovered. When increasing the isothermal pressure of the mobile phase in the interval 100—200 bar at a temperature of 20 °С, the selectivity coefficient of separation of salbutamol enantiomers first increased, then decreased, followed by another increase. Such a behavior is atypical and determines the expediency of using pressure to control selectivity in this kind of chromatography.

Interaction of positional isomers of dimethylbenzene with graphite

The optimized geometries and interaction energies of the intermolecular heterodimers of coronene with o-, m-, and p-dimethylbenzenes (xylenes) calculated by DFT in the PBE0 and B97D functionals were compared. The applicability of coronene as a model for qualitative assessment of the interaction of mononuclear aromatic compounds with the graphite surface was demonstrated. The necessity of including long-range dispersion interactions in DFT calculations of the dimerization energies of aromatic systems was shown. The sorption enthalpies of p- and m-xylenes were shown to be almost equal irrespective of the conditions of the chromatographic experiment. The preferred sorption of p- over m-xylene on graphite is solely due to the entropy factor.