ScienceRise: Pharmaceutical Science

Influence of physicochemical properties and structure of mixed solvents propylene glycol – macrogol 400 on their in vitro release

2023-02-24T20:21:27+02:00

Aim. To study the density and dynamic viscosity of the mixed solvents propylene glycol (PG) – macrogol 400 (M400), to calculate their excess values and excess activation parameters of viscous flow, to evaluate the features of the structure of the mixed solvents and its influence on the in vitro release of PG and M400.

Materials and methods. The mixed solvents PG - M400 were studied over the entire concentration range at temperatures from 293.15 to 313.15 K. The density and dynamic viscosity were determined, and the excess density, excess dynamic viscosity, activation parameters of viscous flow, and excess activation parameters of viscous flow were calculated. The in vitro release of PG and M400 from the mixed solvents was studied using vertical diffusion cells. The content of PG and M400 in the receptor medium was determined by gas chromatography using validated analytical procedures. The release rate, cumulative content, percentage of released PG or M400, coefficients of correlation and coefficients of determination were calculated.

Results. The isotherms of excess density and excess dynamic viscosity of the mixed solvents PG-M400 pass through a maximum. The enthalpy makes the main contribution to the free activation energy of the viscous flow. The excess free energy is positive and has small values; the values of the excess entropy and excess enthalpy are negative, and the isotherms have the minimum at PG concentrations of 70‑75mol %. The release parameters of M400 are greater in binary mixtures where the M400 structure predominates. At PG content of ~75 mol %, the release parameters for PG and M400 are identical. With the increase in PG content above 75 mol %, when the PG structure predominates in the system, the release parameters of PG increase dramatically, and the release parameters of M400 decrease sharply.

Conclusions. The structure of the binary system PG – M400 depends on its composition. Based on the isotherms of excess activation of viscous flow, it is possible to differentiate the areas where the structure of PG or the structure of M400 dominates, or the mixed structure of the binary solvent prevails. The in vitro release parameters for PG and M400 depend on the structure of the mixed solvents. The greatest difference in the release parameters of PG and M400 was observed in the area where the structure of PG dominates

Application of salts of chaotropic anions in the development of hplc methods for the determination of meldonium in dosage forms

2023-02-24T20:51:22+02:00

The aim of the work was to create an approach for the development of HPLC methods for the determination of meldonium in dosage forms with the usage of salts of chaotropic anions in mobile phases.

Material and methods. Analytical equipment: Shimadzu UPLC system LC-40 PDA; Shimadzu Nexera-i LC-2040C 3D-Plus, controlled by software Lab Solution version 5.97, electronic laboratory balance RAD WAG AS 200/C, pH-meter I-160MI. Meldonium dihydrate (purity 99.3 %) was purchased from Sigma-Aldrich (Switzerland), and Vasopro capsules 500 mg were purchased from a local pharmacy. Chromatographic conditions: Agilent Zorbax C-18 SB 150 mm x 4.6 mm 3.5 μm column was used (Agilent Technologies, USA). Mobile phases: 1) 0.25 % KPF₆ w/v – 0.1 % v/v 85 %H₃PO₄ 95 % – 5 % ACN, 2) 0.3 % bis-(trifluoromethane)sulfonimide lithium salt 97 % w/v – 0.1 %v/v 85 % H₃PO₄ 80 % – 20 % acetonitrile. Flow rate - 1mL/min, T=32 °C, detection UV=at 4 channels - 190 nm, 195 nm, 200 nm, 205 nm.

Results and discussion. We have proposed two approaches using two different salts of chaotropic anions - potassium hexafluorophosphate and bis-(trifluoromethane)sulfonimide lithium salt – for the HPLC method development. The chaotropic effects of these anions toward meldonium strongly influenced the analyte migratory behaviour. Both mobile phases involved, in addition to the use of a chaotrope, also the use of acetonitrile and pH adjustment with 0.1 % v/v 85 % H₃PO₄ solution. The detection wavelength (190 nm, 195 nm, 200 nm, 205 nm) was selected experimentally. The results were obtained for 8 concepts. Parameters of the chromatographic system confirm the conclusions and results of this investigation for the influence of chaotropic salts on N-containing molecules in an acidic pH medium, by increasing their retentivity and improving peak shape and uniformity homogeneity, even on the column without end-capping and base-deactivating. Validation of the analytical method was carried out following the requirements of SPhU. Conclusions. HPLC methods for the determination of meldonium in dosage forms have been developed, using positive impacts of chaotropic salts on the molecules containing N-atoms in their molecule on their retentions and peak symmetries on the chromatogram. The validation of the analytical methods showed their suitability for pharmaceutical analysis

Immunohistochemical neuroinflammatory markers in the hippocampus of PTZ-kindled rats under conditions of rapamycin and axitinib treatment

2023-02-28T19:37:29+02:00

The aim of the study is to determine the level of HIF-1α, TNF-α, and NF-kB in the hippocampus of kindled rats treated with rapamycin and axitinib.

Materials and methods. Kindling was produced in 29 rats by administration of three-week pentylenetetrazole (PTZ, 35.0 mg/kg, i.p.). Treatment with rapamycin (0.5 mg/kg, i.p.) and axitinib (2.5 mg/kg, i.p.) was performed for ten days in fully kindled rats. The avidin-biotin-peroxidase method was used for hippocampal slice staining. For negative control, staining was performed using only secondary antibodies.

Results. The HIF-1α expression increased in kindled rats raised by 1.77 times compared to the control (p<0.001). Axitinib treatment resulted in of HIF-1α level of 16.7 % (p<0.05) compared with kindled animals, while combined treatment with rapamycin and axitinib reduced HIF-1α by 33.8 % (p<0.01). In kindled rats, TNF-α expression was 3.74 times greater than in control (p<0.001). Rapamycin treatment reduced TNF-α by 31.0 % (p<0.01). Axitinib treatment caused a reduction of TNF-α by 21.1 % (p<0.05). Combined treatment with rapamycin and axitinib reduced TNF-α by 48.0 % (p<0.001) but still exceeded the TNF-α in control by 1.95 times (p<0.01). NF-kB level in kindled rats exceeded the control by three times (p<0.001). Rapamycin caused a reduction of 19.3 % (p>0.05), while axitinib – by 26.5 % (p<0.05) compared with kindled rats. Combined treatment with rapamycin and axitinib resulted in NF-kB reduction by 56.7 % compared with kindled rats (p<0.001).

Conclusions. PTZ-kindling resulted in an increase in the immunoreactivity of HIF-1α, TNF-α, and NF-kB in the hippocampus. Combined treatment with rapamycin and axitinib engendered prevention of generalized seizures and normalized the level of HIF-1α and NF-kB with a significant reduction of TNF-α. Effects of treatment favours of synergy action of rapamycin and axitinib

The study of carbohydrates of corn raw materials

2023-02-28T19:14:17+02:00

The aim. The aim of the study was to study the content of polysaccharide fractions depending on the dissolution, qualitative composition and quantitative content of sugars in corn silk, leaves and roots.

Materials and methods. To study different fractions of polysaccharides - water-soluble polysaccharides (WSPS), pectin substances (PS), hemicelluloses A (HC A) and B (HM B) used a gravimetric method based on the extraction of polysaccharide fractions with a suitable solvent followed by sedimentation and weighing of the sediment. Determination of the qualitative composition and quantitative content of monosaccharides in corn medicinal plant materials (MPM) was carried out by the method of gas chromatography-mass spectrometry (GC/MS).

Results. Conducted studies of corn silk, leaves and roots carbohydrates using the fractionation method indicate the following trend of BAS accumulation in the studied raw materials: the content of WSPS and PS in corn silk exceeded the content of these compounds in other types of raw materials – 4.07±0.14 % and 7.20±0.29 %, respectively; leaves accumulated the most HC A and HC B compared to the content of these fractions in other samples - 6.81±0.21 % and 21.20±0.84 %, respectively. It was established by the GC/MS method that 4 substances were identified in corn silk in the free state: arabinose, glucose, galactose and fructose. After hydrolysis 5 substances were identified in corm silk - arabinose, xylose, mannose, glucose, galactose. Among the free sugars 3 compounds were found in corn leaves - glucose, fructose and sucrose. After hydrolysis, 4 compounds were identified in in corn leaves – arabinose, xylose, glucose and galactose. In corn roots 3 compounds are found in a free form - glucose, fructose and sucrose. After hydrolysis 4 compounds were identified in corn roots - arabinose, xylose, glucose and galactose.

Conclusions. The obtained results indicate a significant content of polysaccharides and sugars in the raw materials of corn, which makes it possible to predict the anti-inflammatory, detoxifying, adsorbing, energetic activity of the studied types of corn plant raw materials

Macroscopic and microscopic analysis of Alfredia nivea KAR. & KIR herb

2023-02-28T18:35:07+02:00

Kazakhstan flora is rich in promising little-studied plants that are used in folk medicine, but additional deep research is required for their introduction into medical practice with the help of modern scientific techniques. An interesting object for introduction into the official medical and pharmaceutical practice is the Alfredia Nivea Kar. & Kir, family Asteraceae, whose extracts have a neurotropic effect.

The aim. Regarding mentioned above, in order to create new medicines based on the grass of the Alfredia nivea, it is necessary to develop methods of its macro and microscopic identification.

Materials and methods. Macro- and microscopic studies of the grass of Alfredia nivea were carried out in accordance with the methodology of SPhU 2.8.23 "Microscopic examination of medicinal vegetable raw materials". Macroscopic studies were performed using magnifying glass and binocular microscope MBS-9, microscopic-using MS Microscopes 10 (eyepiece X5, X10, X15, lenses x10, x40), micromed XS-4130 (WF15X, Opera, lens X40/0, 65, x10/0,25) with microphoto addon (China).

Results. The morphological and anatomical features of the Alfredia nivea grass. Diagnostic features of the structure of stems, leaves and flowers of this species were revealed.

Conclusions. The macroscopic and anatomical identification parameters of the grass of the Alfredia of Snow. The study of the morphological and anatomical features of the stems, leaves and flowers of Alfredia nivea, considering the requirements of European pharmacopoeia. Diagnostic features of the structure of stems, leaves and flowers of the species were found, which were used as key quality indicators for standardization and identification of raw materials

The pharmaceutical market of medicines containing retinoids for the treatment of psoriasis in Ukraine, Poland and Kazakhstan

2023-02-28T23:37:40+02:00

The aim of the work is to analyze the use of medicines containing retinoids for the treatment of psoriasis on the example of Ukraine, Poland and Kazakhstan.

Materials and methods. The object of the study was antipsoriatic drugs, which are used for the treatment of psoriasis of local and systemic action, and are included in the official register of drugs of the studied countries. Regulatory documents of the State Expert Center of the Ministry of Health of Ukraine were involved in the analysis of the use of medicines for the treatment of psoriasis in Ukraine.

The analysis of the availability of the considered medicines on pharmaceutical markets was carried out according to the data of the official websites of the State Register of Medicines (Ukraine), the Register of Medicines of Poland (Republic of Poland), data of the National Center for Expertise of Medicines and Medical Devices of the Republic of Kazakhstan (Republic of Kazakhstan).

The following methods of logical and meaningful formulation of the problem, office marketing research, content analysis of publications in scientific and practically oriented medical and pharmaceutical publications, comparative analysis, tabular and graphic means of visual presentation of the obtained data were used in the work.

The results. According to the results of the obtained data, an assortment of medicinal products containing retinoids of the studied countries, used for the treatment of psoriasis, was determined. The fate of domestic production in the countries was analyzed, the main active components from the group of retinoids used for the treatment of psoriasis in preparations of systemic and local action were updated.

Conclusions. The role of retinoids in the treatment of psoriasis in Ukraine, Poland and Kazakhstan and the need to develop modern domestic medicines containing retinoids for the treatment of psoriasis have been determined

Technology of obtaining and chemical profiles of dry extracts from leaves of prospective species of the hawthorn genus

2023-02-28T20:55:30+02:00

The aim of the work was to develop a technology for obtaining dry extracts from leaves of non-pharmacopoeia species of hawthorn and establishing their chemical profiles.

Materials and methods. Leaves of Crataegus mollis Sarg., Crataegus submollis Sarg. and Crataegus arnoldiana Sarg., used to obtain the dry extracts, were harvested in the Botanical Garden of the National University named after M. N. Karazina in August 2021. To determine the chemical profiles of the obtained dry extracts, the spectrophotometric method and the high-performance liquid chromatography (HPLC) method were used.

Results. A technological scheme for obtaining dry extracts of hawthorn leaves has been developed. The content of flavonoids and hydroxycinnamic acids in dry extracts of the leaves of C. mollis Sarg., C. submollis Sarg. and C. arnoldiana Sarg. was determined. The content of free amino acids in extracts ranges from 0.70 % to 0.99 %. The content of flavonoids ranged from 7.25 %±0.04 to 8.43 %±0.01, of hydroxycinnamic acids - from 2.35 %±0.02 to 2.85 %±0.03. Rutin, kaempferol-3-O-glycoside, epicatechin and chlorogenic acid were identified in all extracts by the HPLC method. In dry leaf extracts of C. arnoldiana Sarg. and C. mollis identified p-coumaric acid; C. arnoldiana Sarg. – quercetin; C. arnoldiana Sarg. and C. submollis Sarg. – ferulic acid; C. submollis Sarg. and C. mollis Sarg. – quercetin-3-O-rhamnoside.

Conclusions. Dry leaf extracts of C. mollis Sarg., C. submollis Sarg. and C. arnoldiana Sarg. were obtained. For the first time, the content of flavonoids and hydroxycinnamic acids in the extracts was determined by HPLC. It was established that the chemical profile of the obtained extracts is formed by rutin, chlorogenic acid and kaempferol-3-O-glycoside, which can be used in further standardization of these substances. In addition, a comparative study of the amino acid composition of the obtained extracts was carried out for the first time

Optimization of the isolation of biologically active complexes from buds and shoots of birch and poplar buds for their further use in cosmeceutical compositions

2023-03-03T12:49:56+02:00

The aim is to optimize the isolation of biologically active birch and poplar complexes based on woodworking industry waste to study their biological activity to create cosmeceutical compositions that have cosmetic and pharmaceutical effects.

Materials and methods. The object of research is the vegetative organs of birch (buds and shoots) and poplar (buds). In the process of work, experimental studies were carried out on the extraction and separation of natural compounds, development of biological complexes of vegetative organs of birch and poplar, study of the chemical composition and standardization of biologically active complexes of birch and preparations based on them.

Results. The optimal methods for extracting natural complexes were determined. Created as a semi-industrial installation for producing biologically active complexes by barothermal method, combining two processes - high pressure and hydrodistillation. The optimal operating cycle and plant parameters were determined. The optimal solvents for the extraction of biologically active complexes from the vegetative organs of birch and poplar have been determined. Petroleum ether (33.60 %) extracted the most compounds from birch buds, in birch shoots - ethanol (8.34 %). Qualitative and quantitative indicators of biologically active complexes are determined, and projects for examining the obtained biologically active complexes are proposed. We determined the yield of essential oil depending on the time of collection of raw materials and determined that the largest amount of essential oil is contained in spring buds (0.21 % of dry raw materials) and shoots (0.08 %).

Conclusions. Biological complexes created from timber processing waste with high activity are the basis for the creation of cosmetic products. The created semi-industrial plant will provide the basis for creating new original products in industrial volumes.