Objective: Study the influence of the mechanical preparation methods (grinding, fluidization) of solid pharmaceutical substances (PS) and herbal raw material on their physicochemical properties and biological activities. Methods: Test substances and solvents-Lactose monohydrate (DFE Pharma, Germany). Sodium chloride, bendazol hydrochloride (all Sigma-Aldrich, USA) and herbal raw material (Callisia fragrans). The dispersity and native structure of pharmaceutical substances were analyzed by several methods: optical microscopy–Altami BIO 2 microscope (Russia); low angle laser light scattering (LALLS) method (Malvern Instruments, UK); Spirotox method–Quasichemical kinetic of cell transition of cellular biosensor Spirostomum ambiguum; Fourier-transform infrared spectroscopy–the analysis in the middle IR region was carried out using an IR Cary 630 Fourier spectrometer (Agilent Technologies, USA). The analysis of dried leaves of C. fragrans before and after mechanical activation was performed using Shimadzu EDX-7000 X-ray fluorescence spectrophotometer without mineralization (Shimadzu, Japan). Results: It was established that the mechanical change, such as dispersion and drying, alters the biological activity of PS and herbal raw materials. The observed increase in the influence of the dispersed substance on the biosensor S. ambiguum is quantitatively estimated from the values of the activation energy (obsEa), which turns to be valued 1,5 (P≤0,05) times more than for the native form substance. In the study of the dependence of the availability of chemical elements K, Ca, Zn on the degree of dispersion of herbal raw materials was established a quantitative 4-fold (P≤0,05) increase in the concentration of elements in mechano-activated raw materials. Conclusion: By the example of the biological model of Spirotox (single-celled biosensor S. ambiguum) and herbal raw materials obtained from C. fragrans, the increase of biological activity of PS at the dispersion of initial preparations was proved.

This study demonstrates the link between the modification of the solid-phase pharmaceutical substances mechanical structure and their activity in waters with different molar ratio «deuterium-protium». Mechanochemical transformation of the powders of lactose monohydrate and sodium chloride as models of nutrients and components of dosage forms was investigated by the complex of physicochemical and biological methods. The solubility and kinetic activity of substances dispersed in various ways showed a positive correlation with the solvent isotope profile. Substances dissolved in heavy water were more active than solutes in natural water. Differential IR spectroscopy confirmed the modification of substituents in the sample of lactose monohydrate, demonstrating physicochemical changes during mechanical intervention. The biological activity of the compounds was determined by the method of Spirotox. The activation energy was determined by Arrhenius. Compared with the native compound, dispersed lactose monohydrate showed lower activation energy and, therefore, greater efficiency. In conclusion, proposed data confirm the statement that mechanical changes in compounds can lead to physicochemical changes that affect chemical and biological profiles.

It has recently been shown that the titer of the SARS-CoV-2 virus decreases in a cell culture when the cell suspension is irradiated with electromagnetic waves at a frequency of 95 GHz. We assumed that a frequency range in the gigahertz and sub-terahertz ranges was one of the key aspects in the “tuning” of flickering dipoles in the dispersion interaction process of the surfaces of supramolecular structures. To verify this assumption, the intrinsic thermal radio emission in the gigahertz range of the following nanoparticles was studied: virus-like particles (VLP) of SARS-CoV-2 and rotavirus A, monoclonal antibodies to various RBD epitopes of SARS-CoV-2, interferon-α, antibodies to interferon-γ, humic–fulvic acids, and silver proteinate. At 37 °C or when activated by light with λ = 412 nm, these particles all demonstrated an increased (by two orders of magnitude compared to the background) level of electromagnetic radiation in the microwave range. The thermal radio emission flux density specifically depended on the type of nanoparticles, their concentration, and the method of their activation. The thermal radio emission flux density was capable of reaching 20 μW/(m2 sr). The thermal radio emission significantly exceeded the background only for nanoparticles with a complex surface shape (nonconvex polyhedra), while the thermal radio emission from spherical nanoparticles (latex spheres, serum albumin, and micelles) did not differ from the background. The spectral range of the emission apparently exceeded the frequencies of the Ka band (above 30 GHz). It was assumed that the complex shape of the nanoparticles contributed to the formation of temporary dipoles which, at a distance of up to 100 nm and due to the formation of an ultrahigh strength field, led to the formation of plasma-like surface regions that acted as emitters in the millimeter range. Such a mechanism makes it possible to explain many phenomena of the biological activity of nanoparticles, including the antibacterial properties of surfaces.

Objective: Development of a methodology for measuring the deuterium content in water for pharmaceutical purposes by laser light scattering based on ideas about the cluster structure of water. Methods: Samples of industrially manufactured drinking water from different manufacturers with varying deuterium content from 10 ppm to 115 ppm. For the titration of laboratory samples of deuterium depleted water in increments of 5 ppm the following reagents were used: Water, deuterium-depleted (≤1 ppm (D2O, Aldrich, USA); Deuterium oxide/Heavy water/Water-d2 (99.9 atom % D, Aldrich, USA); water Milli-Q (specific resistance 18.2 µS·sm at 25 оС, ТОС ≤ 5 ppb, Merck Millipore). The determination of deuterium content in samples of industrially manufactured water and water obtained in a laboratory manner was carried out by the method of low-angle laser light scattering (LALLS) at the Mastersizer (Malvern Instruments) analyzer and using a working measuring tool–laser dispersion meter/MDL («Cluster-1», Russia/Ukraine). The statistical methods–packages OriginPro®9. Results: It was found that the content of isotopologies in water leads to physicochemical water’s properties changes and morphology changes of giant heterogeneous clusters (GHC). The results of low-angle laser light scattering (LALLS) in the water samples under investigation showed the dependence of the water GHC "dispersibility" expressed in the differentiation of curves of the volume size distribution ("size spectra"), the volume concentration, w%, the laser obscuration values (I ‒I0) as the function of the water isotopic composition variations. The laser diffraction method results correlate with two-dimensional (2D) multi-descriptor mathematical analysis. Conclusion: When identifying deuterium depleted water, it should be considered not only the indicators that determine its pharmacopoeial quality, but also the D/H ratio, because even small changes in the natural isotopic composition of water lead to significant biological effects. Our proposed approach using laser diffraction in combination with mathematical apparatus of (2D) multi-descriptor laser scattering analysis makes possible the exact calculation of individual signs of deuterium depleted water as the pharmaceutical object of study.

Objective: To investigate kinetic changes in the spectral characteristics by Fourier Transform Infrared spectroscopy (FTIR) of water-lactose complexes (SMC), derived during the manufacturing process of the drug, containing release-active forms of antibodies. Methods: lactose monohydrate substance, saturated with release-active forms of affinity-purified polyclonal rabbit antibodies to recombinant human interferon-gamma (RA forms of Abs); tablets produced from this substance by direct compression after the addition of excipients (microcrystalline cellulose, magnesium stearate). Powdered and tableted placebo samples saturated with technologically processed water or phosphate-buffered saline, as well as with intact ethanol were used as control. Kinetic changes in SMC were studied using an Agilent Cary 630 FTIR spectrophotometer with a diamond ATR accessory (Agilent Technologies, USA). We used the method of X-ray fluorescence spectroscopy (EDX-7000 Shimadzu energy dispersive X-ray fluorescence spectrometer) to track changes in the fluorescence signal at certain wavelengths. The range of measured elements–11Na-92U. Results: Control of some technological characteristics of the obtained active substance (moisture, flowability) and dosage form (mean mass, disintegration rate) was used as indirect indicators of quality, but they did not allow reliably distinguishing intact lactose from the saturated one. Long-period oscillations on FTIR spectra were characteristic for all types of samples; oscillations occur at approximately two-week intervals; S/N indices were more stable for samples of RA forms of Abs than for placebo samples. On some days, the substance saturated with RA forms of Abs significantly differed from the intact lactose powder. The kinetics of the X-ray fluorescence intensity at certain wavelengths indicates the possibility of a periodic cooperative trigger transition of the system. Reversible conformational transitions are observed for powders on the 30th and 130th days (Kα 3.313 keV). For tablets at Kα 3.313 keV and Kα 1.740 keV small changes were visualized on those days (100–110th day) when hysteresis phenomena were recorded in the IR spectra of these samples. Conclusion: As a result, the evidence for a long-period dramatic conformational mobility of the water-lactose complex was obtained. Based on the data on the semiannual kinetics of IR spectra, a universal criterion for the identity of lactose powder saturated with RA forms of Abs was obtained. Also, it was confirmed that the lactose conformation state was changed by saturation with RA forms of Abs.