Study of the physicochemical properties of the etravirine substance

Introduction. Etravirine, being one of the most popular antiretroviral drugs, doesn't have its physicochemical properties sufficiently described in scientific publications. Detailed information on the substance properties is necessary both for organizing the synthesis and for justifying the dosage form and technology for its production, as well as for identifying bottlenecks and critical parameters that affect the quality of the finished product.Aim. Study the etravirine physicochemical properties to model the design of studies to create an innovative dosage formMaterials and methods. Etravirine (MSN Life Sciences Pvt. Ltd., Hetero Labs Ltd.). The melting point was determined by the capillary method. Etravirine samples were studied via differential scanning calorimetry (DSC), X-ray powder diffractometry, IR and NMR spectroscopy. Particle size was determined using laser diffraction analysis. The shape and size of the crystals were determined with the help of transmission electron microscopy (TEM). The concentration of etravirine in aqueous media was determined using the HPLC method with a fluorescence detector. The concentration of etravirine in organic solvents was determined spectrophotometrically.Results and discussion. The X-ray powder diffractometry and IR spectroscopy helped to determine the fact that the studied substances represent the same polymorphic modification. The melting point of etravirine ranges from 259 to 263 °C. Melting is accompanied by decomposition. The substance is practically insoluble in aqueous media at pH values in the range from 1.2 to 6.8, soluble in some organic solvents, readily soluble in dimethyl sulfoxide, tetrahydrofuran, dimethylformamide, dimethylacetamide. The distribution coefficient in the "1-octanol/phosphate buffer solution pH 6.8" solvent system was 5.22. The experiment showed that the etravirine substance is lipophilic. Etravirine is found to be a highly crystalline substance and represents needle-shape prismatic crystals.Conclusion. Etravirine is a lipophilic substance, practically insoluble in aqueous solutions, soluble in a number of organic solvents. The studied substances turned out to be the same polymorphic modification. Since the melting of the substance is accompanied by decomposition, high temperatures processes should be avoided.Conflict of interest. The authors declare that they have no obvious and potential conflicts of interest related to the publication of this article.

ISOTHERM OF SOLUBILITY MANGANESE SULFATE - MONOETHANOLAMINE - WATER AT 25 ° C

Solubility in the ternary system manganese sulfate - monoethanolamine - water at 25°C was studied by isothermal method. The equilibrium in the system was controlled by liquid phase analysis. True equilibrium in the system was established within 7 hours. The new compound was isolated in crystalline form and identified by the methods of chemical, graphic, X-ray and thermal analyses. It was found that the new compound is a crystalline substance with an individual set of interplanar distances and line intensities. The formation of the new compound NH2C2H4ON-MnSO4-3H2O which was identified by the methods of chemical, graphic and X-ray analyses has been established. Preliminary agrochemical tests of aqueous solution of the new compound showed its positive properties as a stimulant.

INVESTIGATION OF ANTIMICROBIAL EFFECT OF DECASAN CHLORHEXIDINE AND IODOPHORAM ON STANDARD MICROBIAL STRAINS

The problem of treatment and prevention of infectious-inflammatory post extraction complications in modern surgical dentistry are still challenging, despite the great advances in this field. Many etiological factors are identified as contributing to the development of such complications, but at present scientists are paying much attention to the infectious factor, which is associated with the microflora of the tooth socket after tooth removal. According to the literature, the most common post-extraction complication during an outpatient surgical appointment is alveolitis, which accounts for 1-35% of all cases of tooth extraction. To combat an infectious etiological factor of alveolitis, dental surgeons apply topical antiseptics with a broad spectrum of action such as iodoform and chlorhexidine. As a topical antiseptic drug in the treatment and prevention of oral infectious and inflammatory complications, a domestic antiseptic, Decasan, based on decamethoxine, is becoming more widely applied. Previous studies have shown that this antiseptic has antimicrobial effect against gram-positive and gram-negative, aerobic and anaerobic bacteria; this requires further in-depth studies of its properties, which could be applied in the dental surgical practice to treat and prevent infectious-inflammatory post extraction complications. Chlorhexidine bigluconate is a cationic biguanide. Penetrating into the intracellular membranes of bacteria, it impedes the oxygen consumption and leads to the death of bacterial cells. This antiseptic is widely used in dental practice. Treatment of alveolitis is carried out by using the standard method, namely by using iodoform tamponade of the tooth socket in combination with other medicines. Iodoform (triiodomethane) is a yellow crystalline substance with a strong characteristic odor, practically insoluble in water. In dentistry, this drug is used as an antiseptic in powder form, or combined pastes. The purpose of this in vitro study is to investigate the antimicrobial properties of Decasan, chlorhexidine and iodoform against museum microbial strains. Materials and methods. Museum strains of Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 14990, Enterococcus faecalis ATCC 29212, Esherichia coli ATCC 25922, Candida albicans ATCC 10231, obtained from L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine, were used as studied cultures of microorganisms. The antimicrobial effect of decasan, chlorhexidine and iodoform was assessed by quantitative method of serial dilutions in broth and agar according to the order №167, dated 5.04.2007 On approval of guidelines “Determination of sensitivity of microorganisms to antibacterial drugs". Conclusion. According to the data obtained, decasan and chlorhexidine demonstrate higher bacteriostatic and bactericidal effect on the studied museum microbial strains at a concentration thousands of times lower than the concentration of iodoform.

Morphological study of Nyctanthes arbor-tristis L. fruit and seed in different growth stages

Qualitative and quantitative morphological characterization in different growth stages of Nyctanthes arbor-tristis L. fruits and seeds were investigated. Capsules are compressed, two celled, green, cordate to round or elliptical with one flattened seed in each half. Both LM and SEM study were conducted to gather micromorphological features of matured epicarp and seed testa. Non-glandular, uniseriate, slender trichome and anomocytic stomata were found on epicarp, whereas same was absent on seeds. Some crystalline substance was noticed on both epicarp cells and seed testa. The fruiting stages were divided into 0 to V stages starting from first day of fruit appearing and total required days needed for maturity. Remarkable differences such as fruit and seed size, weight and colour were varied in each stage. Significance of surface micromorphology of matured epicarp and seed testa of N. arbor-tristis is also discussed here. Single-factor ANOVA analysis and Regression were performed to test the significance level of the studied parameters and their relationship.

Production of spiculisporic acid by Talaromyces trachyspermus in fed-batch bioreactor culture

Spiculisporic acid (SA) is a fatty acid-type biosurfactant with one lactone ring and two carboxyl groups. It has been used in metal removers and cosmetics, because of its low propensity to cause irritation to the skin, its anti-bacterial properties, and high surface activity. In the present study, we report an effective method for producing SA by selecting a high-producing strain and investigating the effective medium components, conditions, and environments for its culture. Among the 11 kinds of Talaromyces species, T. trachyspermus NBRC 32238 showed the highest production of a crystalline substance, which was determined to be SA using NMR. The strain was able to produce SA under acidic conditions from hexoses, pentoses, and disaccharides, with glucose and sucrose serving as the most appropriate substrates. Investigation of nitrogen sources and trace metal ions revealed meat extract and FeCl3 as components that promoted SA production. Upon comparing the two types of cultures with glucose in a baffle flask or aeration bioreactor, SA production was found to be slightly higher in the flask than in the reactor. In the bioreactor culture, sucrose was found to be an appropriate substrate for SA production, as compared to glucose, because with sucrose, the lag time until the start of SA production was shortened. Finally, fed-batch culture with sucrose resulted in 60 g/L of SA, with a total yield of 0.22 g SA/g sucrose and a productivity of 6.6 g/L/day.

Production of spiculisporic acid by Talaromyces trachyspermus in fed-batch bioreactor culture

Spiculisporic acid (SA) is a fatty acid-type biosurfactant with one lactone ring and two carboxyl groups. It has been used in metal removers and cosmetics, because of its low propensity to cause irritation to the skin, its antibacterial properties, and high surface activity. In the present study, we report an effective method for producing SA by selecting a high-producing strain and investigating the effective medium components, conditions, and environments for its culture. Among the 11 kinds of Talaromyces species, T. trachyspermus NBRC 32238 showed the highest production of a crystalline substance, which was determined to be SA using NMR. The strain was able to produce SA under acidic conditions from hexoses, pentoses, and disaccharides, with glucose and sucrose serving as the most appropriate substrates. Investigation of nitrogen sources and trace metal ions revealed meat extract and FeCl3 as components that promoted SA production. Upon comparing the two types of cultures with glucose in a baffle flask or aeration bioreactor, SA production was found to be slightly higher in the flask than in the reactor. In the bioreactor culture, sucrose was found to be an appropriate substrate for SA production, as compared to glucose, because with sucrose, the lag time until the start of SA production was shortened. Finally, fed-batch culture with sucrose resulted in 60 g/L of SA, with a total yield of 0.22 g SA/g sucrose and a productivity of 6.6 g/L/d.

Phosphorylation of glycoluryl derivatives with phosphorus pentachloride

The paperpresents the research results on the synthesis and study of new organophosphorus derivatives of glycoluril, obtained on the basis of pentavalent phosphorus. New organoelement phosphorus derivatives synthesized on the basis of N-acyl-substituted glycolurilhave been obtained.They are of considerable interest due to the presence of effective reaction centers. Tetraacetyl-substituted glycoluril —2,4,6,8-tetraacetyl-2,4,6,8-tetraazabicyclo[3,3,0]octane-3,7-dione was chosen as theinitial synthon. Theuse of unsubstituted glycoluril in the reaction of direct phosphorylation by the action of phosphorus trichloride or pentachloride is not possible due to the absence of active phosphorylation centers. It was experimentally shown that the reaction proceeds with prolonged heating for at least 48 hours in an argon. Theinitial acyl derivative of glycoluril and phosphorus pentachloride in theratio of 1:6 and leads to the formation of diphosphonic complex of tetraacetylglycoluril —dihexachlorophosphorate 2,6-diacetyl-(4,8-diacetyl-2,4,6,8-tetraaza-bicyclo[3.3.0]octane-3,7-dione)-2,6-di(chloroethenyltrichlorophosphonium). The obtained compoundis a white crystalline substance unstable in air. Decomposition of the diphosphonic complex was carried out using benzaldehyde and proceeds with the formation of the corresponding dichlorophosphate derivative, also unstable in air and rapidly decomposing at room temperature.

Weakened Lattice-Strain Effect in MoOx@NPC-Supported Ruthenium Dots toward High-Efficiency Hydrogen Generation

Designing conductive amorphous buffer layer between crystals (or lowering the crystallinity of one component) to minimize lattice-strain influence between highly crystalline substance and nearby constitute, alleviating the lattice strain thus...

Synthesis and study of the reactivity of 1,1'-oxalyl di(2-methylimidazole) in reactions with N-nucleophiles

This article describes the synthesis of 1,1'-oxalyl di(2-methylimidazole), which was obtained in two stages. At the first stage of the synthesis, 1-trimethylsilyl-2-methylimidazole and oxalyl chloride were obtained. At the second stage of the synthesis, the target product was obtained by reacting 1-trimethylsilyl-2-methylimidazole with oxalyl chloride. The product was a dark crystalline substance, the yield of the final product was 83%. The structure of 1,1'-oxalyl di(2-methylimidazole) was confirmed by IR and 1H NMR spectroscopy. In the IR spectra, characteristic absorption bands were found, confirming the presence of the corresponding functional groups in the structure of the compound, in the 1H NMR spectrum, proton signals with characteristic chemical shifts for the corresponding functional groups were found. The PASS online software predicted the types of biological activity of the compound under study. The most probable possibilities of application in the treatment of urological diseases, diabetes mellitus, staphylococcal, oncological diseases, antiaggregatory action. For the 1,1'-oxalyl di(2-methylimidazole) molecule, 6 conformers were found, which were three pairs of enantioconformers in the Molecular Operating Environment 2009.10 software, for which the electrostatic potential, nucleophilic and electrophilic susceptibility surfaces were calculated in the SCIGRESS Modeling 3.1.4 software. It was shown that the interaction with nucleophilic reagents is most typical for the 1,1'-oxalyl di(2-methylimidazole) molecule. Calculations of the potential energy of the conformers of 1,1'-oxalyl di(2-methylimidazole) molecules have been carried out. Using 1,1'-oxalyl di(2-methylimidazole), the syntheses of acetanilide, benzanilide and diethylformamide were carried out. These syntheses were carried out in order to test the reactivity and the possibility of amide-type bond formation upon activation of the carboxyl group in carboxylic acids. The reactions were carried out in one stage without isolation of the intermediate 2-methylimidazolide of the corresponding carboxylic acid. In this case, the proposed reaction mechanism should be two-stage. Possible structures of reactants, transition states, and reaction products in the interaction of 1,1'-oxalyl di(2-methylimidazole) with carboxylic acids and amines have been calculated by methods of computational chemistry.