O. O. Parenago

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.

Micronization of levofloxacin by supercritical antisolvent precipitation

The process of micronization of levofloxacin (LF, an antibacterial agent of the fluoroquinolone group) by the supercritical antisolvent precipitation technique (SAS) was investigated. It was shown that LF particles of different sizes (from 1 to 10 μm) and of various morphologies (from thin plates to elongated parallelepipeds) can be produced depending on the type of solvent used for conducting micronization. Investigation of the micronized LF preparations using the methods of IR-Fourier spectroscopy, Raman scattering, and circular dichroism showed that the LF micronization caused neither changes in its chemical structure nor racemization. Micronization of LF significantly affects the rate of its dissolution in model systems exhibiting effects dependent on the type of the solvent used for micronization. For example, the highest rate of dissolution at pH 4 was observed for LF preparations micronized with the help of chlorohydrocarbons. It was shown that the rate of dissolution of all micronized LF preparations was higher by 15–30% in comparison with the initial LF, which likely was related to the changes in the degree of crystallinity/amorphousness, as well as of morphologies of microparticles formed in the SAS process.

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.

Photo–induced processes in Ag and Eu β-diketonates incorporated into aerogel matrix of silicon dioxide by supercritical fluid impregnation

Samples of silicon dioxide aerogel with embedded Ag and Eu β-diketonate molecules are obtained by impregnation in supercritical carbon dioxide (SC-CO2). The sample impregnated by Eu(tta)3 molecules possesses photoluminescence properties. Moreover, adsorption of Eu(tta)3 on the walls of the pores results in a strong broadening of the Stark components of its photoluminescence spectra. It is found that aerogel impregnation by AgFOD molecules followed by laser irradiation causes the formation of Ag nanoparticles in the sample volume as a result of AgFOD photolysis and subsequent diffusion self-assembly. The Ag nanoparticles assemble into filament structures due to self-organization as they focus laser radiation.

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.

Effect of additives on eremomycin sorbent selectivity in separation of salbutamol enantiomers using supercritical fluid chromatography

A regime is found in which chiral stationary phase based on macrocyclic glycopeptide eremomycin allows separation of salbutamol sulfate enantiomers in supercritical fluid chromatography. Enantioseparation occurs only when two dynamic modifiers are used simultaneously: isopropylamin + trifluoroacetic acid or isopropylamin + ammonium acetate. Amine molar concentration in mobile phase has to be higher than acid molar concentration, otherwise enantiomers coelute. We suppose that with amine excess a mechanism of enantiorecognition is realized which involves ionic sorbent-sorbate interactions. Such mechanism is well-known for glycopeptide chiral selectors in liquid chromatography, but for supercritical fluid chromatography it is reported for the first time.

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.