ScienceRise: Pharmaceutical Science

Development of the composition of aqueous extract of lespedeza bicolor and gel with extract and mangiferin

Fri, 28 Feb 2025 00:00:00 +0200

The aim of the work: research on the development and standardization of an aqueous extract of the aerial part of Lespedeza bicolor and the study of pharmacotechnological parameters of a gel with the extract and mangiferin.

Materials and methods: in the studies on obtaining an aqueous extract, the aerial part of Lespedeza bicolor, harvested in the Botanical Garden of the Ivan Franko National University of Lviv (Lviv, Ukraine) in the flowering phase, was used. Identification and quantitative content of biologically active compounds in the experimental samples of the extracts were carried out by chemical reactions, thin-layer chromatography and absorption spectrophotometry. The results obtained were used to standardize the selected aqueous extract of Lespedeza (AEL).

In the development of the gel, AEL, mangiferin (China, X’ian Pincredit Bio-Tech Co., Ltd. QC004) and excipients of domestic and foreign production were used. The studies used physicochemical (pH value) and pharmacotechnological research methods (thermo- and colloidal stability, dispersion analysis, dialysis method through a semipermeable membrane).

Results. The conditions for obtaining AEL were experimentally substantiated. It was shown that the use of three-stage remaceration with infusion for 60 minutes at a temperature of 90-100 ºC ensures maximum extraction of polyphenolic compounds. The TLC method identified the presence of rutin, quercetin, chlorogenic and caffeic acids, tannins and substances of polysaccharide structure in the extract. Methods for quantitative determination of polyphenolic compounds and flavonoids by absorption spectrophotometry were developed. Based on the results of microscopic analysis, study of the osmotic activity of the base and the dynamics of mangiferin release, the composition of a dermatological gel was proposed, containing AEL, mangiferin, PEO-400, ethanol 96 %, corn oil, tween 80, carbopol, trometamol, purified water.

Conclusions. The conditions for obtaining and standardizing the aqueous extract of Lespedeza bicolor were substantiated. The composition of the gel with mangiferin and AEL was proposed. It was shown that the introduction of 20 % PEO-400, 10 % ethanol 96 % and 1 % tween-80 into the gel base ensures its absorption capacity and increases the rate of mangiferin release

Analysis of the current status of probiotic drug development

Fri, 28 Feb 2025 00:00:00 +0200

The aim of the work is to analyze the current state of the creation of probiotic preparations.

Materials and methods. The work analyzes strains of probiotic bacteria Lactobacillus, Bifidobacterium, Streptococcus, Bacillus, Saccharomyces and other genera. Methods for obtaining probiotics are considered, including the selection of producer strains, the scheme and parameters of culturing producers, collection and concentration, lyophilization, formulation of the product composition, selection of the dosage form. Following technological methods for obtaining dosage forms of probiotics are used: capsules, emulsions, hydrogels, suppositories, tablets, etc.

Results. The main functions of probiotics in various parts of the human body are considered. Bacterial strains that are part of prophylactic and medicinal preparations are analyzed. The creation of new probiotic preparations is carried out in several directions: the creation of recombinant microorganisms by genetic engineering methods and the development of new generation therapeutic preparations to improve human health, as well as the development of probiotic delivery systems into the human body. Engineered probiotics are a type of new microorganisms obtained by modifying the original bacteria and yeast. The possibility of using a new generation of strains (Akkermansia muciniphila, Ruminococcus bromii, etc.) that demonstrate high therapeutic potential in the treatment of metabolic diseases is discussed. New data and a deep understanding of the microbiome have helped to identify useful commensals and their therapeutic potential. The prospects for the use of probiotics, prebiotics and postbiotics in preparations, including a new generation of probiotic strains, are shown. The effectiveness of probiotic products for restoring the microflora of the oral cavity, intestines and vagina in various dosage forms was assessed: hydrogels, capsules and tablets.

Conclusions. Functional products of probiotic and postbiotic origin have antiviral, antibacterial and antitumor activity. Probiotics are effective and safe, have high therapeutic potential for the prevention and treatment of diseases of various etiologies. Various dosage forms of probiotics are highly effective for restoring the microbiome of the human body. The prospects for the use of various probiotic strains, including a new generation of microorganisms, are discussed

Development of the composition of a dermatological product in the form of a cream with extracts of the aerial part of lespedeza bicolor

Fri, 28 Feb 2025 00:00:00 +0200

The aim of the work: Justification of the composition of emulsion cream with extracts of Lespedeza bicolor.

Materials and methods: In the development of the emulsion base of the cream, corn oil (Ukraine), propylene glycol (Germany), purified water, emulsifiers: xyliance (France), prolipid 141 (USA) and lamecrem (France) were used. The composition of the emulsion base included oil and liquid alcohol extract of the above-ground part of Lespedeza bicolor, which were obtained from the above-ground part of Lespedeza bicolor, harvested in the Botanical Garden of the Ivan Franko National University of Lviv (Lviv, Ukraine) in the flowering phase. The studies used physicochemical (pH value, identification and quantitative content of BAS), pharmacotechnological (thermo- and colloidal stability, structural-mechanical properties and disperse analysis) research methods. The anti-inflammatory activity of the experimental samples was studied on a burn wound model in outbred sexually mature male rats. The following medicines were used as comparison drugs: Panthenol ointment, “Hemofarm”, AD, Serbia, series 138CLA and Calendula ointment, LLC “Pavlova Pharmacy”, Ukraine, series 23.0823.

Results. Experimental studies of the organoleptic, physicochemical and structural-mechanical properties of samples of emulsion bases showed their dependence on the concentration of the oil phase, the composition and concentration of complex emulsifiers xyliance, prolipid 141 and lamecrem. It was established that the emulsion base of the cream, which contains 15 % corn oil, 7 % of the complex emulsifier xyliance, 5 % propylene glycol and water purified to 100, has satisfactory structural-mechanical properties, the necessary dispersion and homogeneous distribution of particles of the oil phase in the aqueous dispersion medium, withstands the test for thermal and colloidal stability and can be used to develop a dermatological cream with Lespedeza extracts. It was shown that the introduction of extracts into the composition of the developed base does not affect the stability, structural-mechanical properties of the base and the content of BAS. Studies of the anti-inflammatory activity of a cream with a complex of biologically active compounds of the oily and alcoholic extracts of the terrestrial part of Lespedeza bicolor on a burn wound model showed a reduction in signs of inflammation without signs of the joining of an infectious process in laboratory animals with wound healing on the 26th day of the study.

Conclusions. The composition of the cream with oil and alcohol extract of Lespedeza, which, due to the BAS complex, has a wider spectrum of pharmacological activity, has been experimentally substantiated. The composition of the emulsion base of the cream with corn oil, xyliance emulsifier, propylene glycol and purified water has been developed. It has been shown that the introduction of extracts into the composition of the developed base does not affect its pharmacotechnological properties, and the quantitative content of biologically active compounds in the cream corresponds to their content in the extracts in terms of the concentration of extracts in SDF, which is a confirmation of the compatibility of BAS with excipients. It has been established that the cream containing the BAS complex of Lespedeza bicolor in terms of anti-inflammatory activity is at the level of the comparison preparations Panthenol ointment and Calendula ointment

Polymer solid dispersion system of nimesulide: in vitro dissolution assessment, thermodynamic and physicochemical characteristics

Fri, 28 Feb 2025 00:00:00 +0200

Nimesulide is a well-known non-steroidal anti-inflammatory active pharmaceutical ingredient (API), but it is poorly soluble in water, which makes its bioavailability relatively low.

The aim of the work was to investigate the effect of polyvinylpyrrolidone (PVP) of different molecular weights on the phase solubility of nimesulide and to evaluate the thermodynamic parameters of the obtained complexes in order to determine the optimal polymer for further development of a solid dispersed system (SDS) of nimesulide and to study its physicochemical properties, which lead to an improvement in the solubility of API in the composition of the obtained composite material.

Materials and methods. The dependence of the nimesulide dissolution profile in water on the concentration of PVP of different molecular weights was studied by the Higuchi and Connors method. SDS was prepared by the «green» method of solvent evaporation and were characterised by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) and were evaluated for dissolution profiles.

Research results. The influence of PVP of different molecular weights on the phase solubility of nimesulide was studied, and it was found that the best increase in solubility in water was observed in the system with PVP K-25 – 5.27 times. Thermodynamic parameters of this composition were also investigated. The FTIR results indicate that the formation of complexes between the API and the polymer is predominantly due to hydrogen bonds. DSC and PXRD showed that nimesulide is present in SDS in an amorphous form. The results of the in vitro release kinetics study showed that the release rate of nimesulide from the formed SDS was higher than the dissolution rate of the comparison drug.

Conclusions. A solid dispersed system prepared by the «green» method of solvent evaporation using PVP K-25 as a carrier can be used as a good strategy for formulating effective anti-inflammatory drugs of nimesulide with increased bioavailability

Comparative analysis of polysaccharides of Rosa × damascena Mill. buds and flower petals

Fri, 28 Feb 2025 00:00:00 +0200

The aim. The aim of the work was a comparative study of polysaccharides of Rosa × damascena buds and flower petals after obtaining essential oils.

Materials and methods. The water distillation technique was used to determine the essential oils (EO) content in buds and flower petals of R. × damascena. The content of water-soluble polysaccharides (WSPS) and pectins (PC) from buds and flower petals of R. ×damascena was obtained using the fractionation method after EO were isolated. Free and bound monosaccharides in WSPS from R. × damascena buds and flower petals were determined by gas chromatography-mass spectrometry (GC/MS) method. Agilent 6890N / 5973 inert gas chromato-mass spectrometric system (Agilent Technologies, USA) was used for the chromatographic separation with HP-5ms capillary column (30 m × 0.25 mm × 0.25 mm, Agilent Technologies, USA). The filtrates obtained after WSPS precipitation of buds and flower petals were analyzed by chemical reactions.

Results. The results showed that the EO concentration in buds and flower petals of R. × damascena was 0.033 ± 0.005 % and 0.015 ± 0.002 %, respectively. The WSPS content was 10.33 ± 0.31 % in buds and 9.69 ± 0.25 % in flower petals. In addition, the PC content in buds was 4.35 ± 0.14 % and in flower petals 7.88 ± 0.15 %. GC/MS analysis revealed that WSPS from buds of R. × damascena composed of monosaccharides arabinose, fucose, mannose, glucose, galactose, and inositol. WSPS of R. damascena flower petals consist of arabinose, fucose, glucose, galactose, and inositol. Glucose is present in a higher amount. Analysis of the filtrate of buds and flower petals obtained after WSPS precipitation by chemical reactions shows the presence of flavonoids, tannins and triterpene saponins.

Conclusions. The total content of WSPS in flower buds did not significantly exceed the content of these compounds in flower petals of R. × damascena. The PC content in flower buds was significantly lower (4.35±0.14 %) than in flower petals (7.88±0.15 %). It can be assumed that WSPS and PCS could be responsible for the high swelling index.

The study of WSPS by GC/MS indicates the predominance of glucose and galactose in both types of raw materials, as well as differences in the qualitative and quantitative content of monosaccharides in the composition of WSPS of flower buds and flower petals.

The study of the filtrate of flower buds and petals of R. × damascena, obtained after precipitating WSPS by chemical reactions, indicates the presence of phenolic compounds and triterpene saponins.

The results obtained indicate the possibility of obtaining WSPS, PC, and an extract rich in phenolic compounds and triterpene saponins after extraction of EO from buds and flower petals of R. × damascena by hydrodistillation

Design, synthesis, molecular docking, and antioxidant properties of a series of new S-derivatives of ((1,2,4-triazol-3(2H)-yl)methyl)thiopyrimidines

Fri, 28 Feb 2025 00:00:00 +0200

The aim of our work is to synthesize new S-derivatives in the series of ((1,2,4-triazol-3(2H)-yl)methyl)thiopyrimidines and to study their antioxidant activity, to identify the most promising compound using molecular docking and kinetic parameters.

Materials and methods. The ¹H and ¹³C NMR spectra were recorded on a Bruker AC-500 spectrometer. LC-MS was recorded on an Agilent 1260 Infinity HPLC system equipped with a diode-array detector and proton ionization. Elemental analysis (C, H, N, S) was performed on an ELEMENTAR vario EL cube. Molecular docking was performed using the AutoDock 4.2.6 program. Free radical absorption was measured using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical assay.

Results. A series of S-acyl derivatives of 4-methyl-5-((pyrimidin-2-ylthio)methyl)-4H-1,2,4-triazole-3-thiols were synthesized through alkylation and subsequent cyclization. The structure of the obtained compounds was confirmed by ¹H and ¹³C NMR spectroscopy. Antiradical activity was evaluated using the DPPH test, with compound (6) exhibiting the highest activity, surpassing ascorbic acid. Molecular docking with cytochrome c peroxidase (PDB: 2X08) confirmed strong binding interactions, highlighting the potential of these derivatives as antioxidants.

Conclusions. Three compounds (1, 6, 8) exhibited higher activity than the reference drug, the natural antioxidant ascorbic acid. This high activity may be associated with the presence of pharmacophore fragments, particularly the pyrimidine skeleton and the sulfur atom linked to the 1,2,4-triazole. The IC₅₀ for the most active compound was calculated as 4.458±1 µM, which is 27 times more effective than ascorbic acid. Molecular docking results showed that compounds 4 and 6 had the lowest binding energies, making them the most effective compounds in terms of antioxidant activity

Synthesis, anticancer properties evaluation and in silico studies of 2-chloro- and 2,2-dichloroacetamides bearing thiazole scaffolds

Fri, 28 Feb 2025 00:00:00 +0200

The aim. The study aimed to synthesize and evaluate the anticancer activity of a series of 2-chloro- and 2,2-dichloroacetamides bearing thiazole scaffolds. Particular attention was paid to their cytotoxic effects, chemical properties, and action mechanisms, with a focus on glutathione S-transferase (GST) inhibition as a potential pathway for anticancer activity.

Materials and methods. The compounds were synthesized using acylation reactions and characterized via ¹H and ¹³C NMR spectroscopy as well as LC-MS. Their cytotoxicity was assessed using the MTT assay across cancer and pseudo-normal cell lines. Quantum-chemical calculations were performed using DFT, while molecular docking studies analyzed interactions with GST to explore their interaction.

Results. Among the synthesized derivatives, 2-chloroacetamides exhibited significant cytotoxic activity against human acute T cell leukemia (Jurkat) and triple-negative breast cancer (MDA-MB-231) cell lines, as well as Ba/F3 cells with calreticulin mutations. In contrast, 2,2-dichloroacetamides showed negligible activity across all tested cell lines. Quantum-chemical analysis indicated that structural and electronic differences between these two compound classes likely influence their bioactivity. Molecular docking studies revealed higher binding affinities of glutathione-2-chloroacetamide conjugates to GST, compared to the reference glutathione-etacrynic acid complex, suggesting GST inhibition as a potential mechanism underlying their anticancer effects.

Conclusions. The synthesized 2-chloroacetamides demonstrate promising potential as anticancer agents, likely due to their ability to form inhibitory conjugates with glutathione, thereby affecting GST activity. These findings underline the importance of further studies to optimize these compounds for therapeutic use

Analyst qualification for the aliquot sampling operation under conditions close to routine analysis

Fri, 28 Feb 2025 00:00:00 +0200

Aim. This study aimed to assess the performance of analysts conducting the standard aliquot sampling operation with a pipette in an inter-laboratory trial under conditions closely resembling routine analytical practices.

Materials and methods. Certified 2 mL Mohr pipettes ISO class A; a gravimetric procedure for determining the delivered volume and the corresponding equipment that meets the ISO 4787:2021 requirements; the State Pharmacopoeia of Ukraine statistical approaches.

Results and discussion. The testing involved 25 analysts from 6 laboratories performing volume measurements using characterized pipettes in a "blind" experiment (the analyst was unaware of the testing, and the supervisor instructed them to work according to routine procedures). Acceptance criteria were developed based on reliable glassware verification and compliance with the requirements of normal analytical practice (NAP) regarding individual volume deviations from the certified value.

The average volume deviation did not meet ISO requirements for 40 % of participants (incorrect volumetric glassware verification), individual deviations exceeded NAP requirements for 68 % of participants (incorrect routine analysis performance), and the standard deviation for replicate volume measurements exceeded the requirements for 32 % of participants (unreliable volumetric glassware verification).

Conclusion. The "blind" testing revealed a significantly higher level of non-compliance compared to traditional proficiency testing (PT). This confirms our assumption that the results of traditional PT reflect the laboratory's best capabilities rather than routine testing practices and cannot be used to assess uncertainty in routine analysis. "Blind" testing provides a more realistic assessment of uncertainty in routine analysis. The high level of non-compliance calls for corrective actions across the entire pharmaceutical sector rather than in individual laboratories

Research on the development of the composition of complex action dental films with calcium hydroxyapatite

Fri, 28 Feb 2025 00:00:00 +0200

The aim. Development of the composition of dental films for remineralization, treatment and prevention of dental hyperesthesia, prevention of the formation of microbial biofilms, elimination of pathogenic microflora.

Methods. Determination of crystallographic characteristics, uniformity of particle distribution and their ability to aggregation was carried out by microscopy, viscosity – by rotational viscometer, pH-potentiometrically. The tensile strength of the films, the ability to stretch and lengthen, the strength of the bioadhesive bond were investigated by a texture analyzer, the thickness of the films – by calipers. Antimicrobial activity was determined by the disk-diffusion method and by the effectiveness of antimicrobial preservatives.

Results. The choice of CHA concentration (10 %) was based on the analysis of literature sources. Structural-mechanical and organoleptic studies established the feasibility of using a combined system with the inclusion of purified water, glycerin and macrogol 400. The study of sedimentation and aggregation stability of the samples showed a uniform distribution of particles in samples from PVA, HEC, HPC. Films from Sodium Alginate, PVP, Na-CMC and HPMC were excluded from the work due to unsatisfactory properties. Structural-mechanical and physico-chemical properties allowed us to choose 5 % PVA as the film former, and 4 % glycerin as the plasticizer. The concentrations of API (metronidazole and chlorhexidine) were selected based on antimicrobial activity and preservative effect.

Conclusions. As APIs, CHA – a remineralizing, anti-caries agent, metronidazole and chlorhexidine – antimicrobial components were selected. The introduction of CHA is rational in a complex dispersion medium, metronidazole as a suspension with glycerin, chlorhexidine as a 20 % solution. The composition of the film base was substantiated. The concentrations of metronidazole and chlorhexidine bigluconate were determined. The developed drug met the specifications of the MQC

Research in component composition of the volatile fractions from the genus Anemone plants

Liliia Tuzin, Andriy Grytsyk, Thanh Tung Nguyen, Ain Raal, Oleh Koshovyi — Fri, 28 Feb 2025 00:00:00 +0200

Plants of the genus Anemone L. of the Ranunculaceae family are perennial herbaceous plants. The genus includes about 200 species, five of which are growing on the territory of Ukraine. Despite their relatively wide distribution and availability of raw materials, plants of this genus remain insufficiently studied.

The aim. The aim of the work was to conduct comparative research on the volatile substances in A. nemorosa L. and A. ranunculoides L. raw materials harvested in Ukraine.

Materials and Methods. Hydrodistillates obtained from dried herb and rhizomes of A. nemorosa L. and dried herb of A. ranunculoides L. were analyzed using gas chromatography-mass spectrometry (GC/MS).

Research results. The investigation identified 68 and 50 compounds in A. nemorosa and A. ranunculoides raw materials, respectively. The key classes of organic compounds in the compositions of volatile fractions of the studied samples are: aldehydes (30.9 – 42.4 %), monoterpenoids (6.1 – 15.5 %), organic acids (4.2 – 15.8 %), aliphatic and aromatic hydrocarbons (0 – 8.7 %), sesquiterpenoids (7.9 – 18.9 %), diterpenoids (1.9 – 6.1 %), esters (1.8 – 4.4 %), aromatic compounds (4.4 – 7.9 %), alcohols (4.4 – 9.1 %) and ketones (4.4 – 9.1 %). The main components of the volatile fractions of A. nemorosa were identified as hexahydrofarnesyl acetone, dibutyl phthalate, phytol, hexanal, 2-pentylfuran, and (E)-β-ionone. For A. ranunculoides, the basic compounds were hexahydrofarnesyl acetone, n-hexadecanoic acid, phytol, phthalic acid, and pelargonaldehyde.

Conclusions. The component composition of volatile fractions in 11 samples of Anemone L. species from the flora of Ukraine was analyzed using the GC/MS method. It has been found that the A. nemorosa rhizomes contain the highest level of volatile fraction. The analysis of the component composition of volatile fractions in Anemone species indicates the prospects for further research in this plant species, their pharmacological activities, and their applications

Study of the chemical components of CO2 extracts from the underground part of Ferula Asafoetida L.

Fri, 28 Feb 2025 00:00:00 +0200

The aim of this study was to determine the chemical composition of the CO₂ extract obtained from the underground part of Ferula asafoetida L., a plant widely used in traditional Kazakhstani medicine, with a particular focus on the amino acid and fatty acid profiles.

Materials and methods. The plant material was collected in accordance with current Good Agricultural and Collection Practice (GACP) guidelines and underwent thorough pre-processing. A subcritical CO₂ extraction method was applied to preserve thermolabile and volatile components while minimizing solvent residues. Chemical analysis was performed using GC-MS, and the amino acid and fatty acid profiles were determined by gas-liquid chromatography (GLC) based on standardized methods.

Results. The resulting CO₂ extract had a high proportion of unsaturated fatty acids (90.2 %), primarily oleic acid (46.1 %) and linoleic acid (43.0 %), along with a complete set of 20 amino acids, including 25.92 % essential amino acids. The major bioactive compounds identified were 9,12-Octadecadienoic acid, ethyl ester (18.61 %) and ethyl oleate (13.18 %), which have potential antioxidant and anti-inflammatory properties. These findings suggest the extract’s suitability for pharmaceutical and nutraceutical applications.

Conclusions. Although the extract shows promising potential for pharmaceutical applications, further verification through comprehensive pharmacological studies is necessary

Study of the potential antipsoriatic effectiveness and safety of the combination of naftalan oil with salicylic acid in cellular test systems

Ganna Zaychenko, Iryna Stan, Pavlo Simonov, Oksana Sinitsyna, Oksana Simonova — Fri, 28 Feb 2025 00:00:00 +0200

The aim of this work was to evaluate the combination of purified naftalan oil (PNO) with salicylic acid (SA) for topical application as a potential effective antipsoriatic ointment and to study the mechanism of its action using specific in vitro cell models.

Material and methods. The effectiveness and safety of the following dosage forms were studied: ointment with 10 % PNO and 3 % SA (PNO-SA), cream with 0.064 % betamethasone dipropionate (BD), and ointment with 3 % SA. Cell viability of original HaCaT human keratinocytes and modified HaCaT/P was determined by colorimetric methods, namely by crystal violet staining or the MTT test method. The level of apoptosis of cells was evaluated by flow cytometry. Production of pro-inflammatory cytokines IL-8 and IL-1β was measured by the ELISA method.

Results. It was shown that the sensitivity of cells with a psoriasis-like phenotype (HaCaT/P) to PNO increases statistically significantly compared to control cells, which was confirmed by both the cell viability and the MTT test. to obtain a result with inhibition of cells with psoriasis-like characteristics, HaCaT/P requires a smaller concentration of the drug compared to a similar effect on conditionally normal cells – HaCaT. This may indicate the relative safety of the proposed medicinal product (combination) in parallel with the conditions of its effectiveness concerning pathologically changed cells. The results of flow cytometry showed that the new PNO-SA complex causes a statistically significant increase in the percentage of cells in all phases of apoptosis compared to control cells. Finally, a statistically significant decrease in the production of IL-8 by cells with psoriasis-like characteristics – the HaCaT/P line was shown in the presence of the PNO-SA combination compared with control cells. In addition, there was a significant decrease in the level of IL-8 production in cells in the presence of the combination compared to SA and the comparator BD. However, in terms of its effect on IL-1β production, the PNO-SA combination proved to be inactive.

Conclusion. Our proposed combination (PNO-SA), which suppresses pro-inflammatory IL-8 by more than 2 times (by 67.4 %) compared to the control, is a promising potential option for local treatment of psoriatic lesions. We speculate about the future demand of this combination in the clinical setting because along with high efficiency (in terms of viability indicators – the number of living cells, the level of apoptosis) towards pathologically changed keratinocytes, it shows a low toxicity profile towards normal healthy keratinocytes