ScienceRise: Pharmaceutical Science

Study of aqueous solutions of poloxamers by rotational viscometry and spin probe method

Nikolay Lyapunov, Elena Bezuglaya, Oleksii Liapunov, Oleksii Lysokobylka — Thu, 31 Aug 2023 00:00:00 +0300

The aim. To study aqueous solutions of different poloxamers by spin probe method and rotational viscometry depending on the temperature and poloxamer content.

Materials and methods. The aqueous solutions of poloxamers 188, 237, 338 and 407 were studied. The solutions were studied by rotational viscometry at different temperatures; the flow behaviour, yield stress (t₀), and dynamic or apparent viscosity (η) were determined. Five spin probes differing in molecular structure, solubility, and radical localisation were introduced into the solutions. Electron paramagnetic resonance (EPR) spectra were obtained. The EPR spectra were used to determine their type and to calculate parameters.

Results. Three factors are important for gel formation: the poloxamer type, its concentration in aqueous solution, and temperature. As the temperature of aqueous solutions of poloxamers 237, 338, and 407 increases, the rotational correlation times of fatty acid-based spin probes and the order parameters of their EPR spectra decrease. This indicates a decrease in the packing density and orderliness of the polypropylene oxide (PPO) chains in the non-polar part of the poloxamer associates, leading to an increase in the volume fraction of micelles/mesophases and promoting the formation of gels. As the temperature decreases, the opposite processes occur, leading to a gel → sol transition. At 37 °C, non-polar micelle cores could be characterised as two-dimensionally liquid and one-dimensionally solid. The rotational correlation times of the hydrophilic spin probe 4-OXO-TEMPO in 25 % aqueous solutions of poloxamers 338 and 407 are approximately constant or increasing despite an increase in the temperature. This indicates that in the polar part of the poloxamer associates, where this probe is partially localised, structural rearrangements occur with increasing temperature, which probably prevents hydrophobic hydration of the PPO chains.

Conclusions. The rheological properties of aqueous solutions of poloxamers depend on their type, concentration, and temperature. According to the parameters of the EPR spectra of fatty acid-based spin probes, it was found that with increasing temperature, the packing density and the orderliness of the PPO chains in the non-polar part of the poloxamer associates decrease, probably leading to an increase in the volume of the micelles and causing a sol → gel transition

Experimental research on the development of composition of complex action ointment based on phytocomplex

Thu, 31 Aug 2023 00:00:00 +0300

The aim of the work is to develop the composition of a complex action ointment based on active pharmaceutical ingredients of natural origin for the treatment of cheilitis of various etiologies.

Materials and methods. The development of the ointment base by selecting active pharmaceutical ingredients and auxiliary substances determined by organoleptic, physicochemical, rheological and microbiological research methods.

Results. Studies of the antimicrobial activity of experimental samples have established that the optimal ointment base is a water/oil emulsion, which provides better API release rates than absorption bases.

According to the results of structural and mechanical studies, the introduction of the API complex reduces the structural viscosity of the ointment base. Furthermore, the ability of the ointment to thin out with an increase in the gradient of the shear rate is shown, which will contribute to the uniform distribution of the API during the technological process and the easy application of the ointment to the skin.

The study of textural properties of the experimental ointment samples (cohesion, adhesion, and elasticity) also confirmed the satisfactory spreadability of the sample. The optimal container for its consistent properties was chosen according to the results of the ointment's structural, mechanical and textural properties.

A test of the effectiveness of antimicrobial preservatives was conducted, resulting in the minimum effective concentration of sodium benzoate in the amount of 1 % was substantiated. Furthermore, based on the results of a complex of studies, the composition of the emulsion ointment was developed, which includes vaseline (liquid paraffin) 20 %, emulsifiers glycerol monostearate 5.5 %, polysorbate-80 3.5 %, viscosity regulator of the aqueous phase hydroxyethyl cellulose 3 %, phytocomplex API "Phytol" (concentrated aqueous extract of burdock root: oak bark: pot marigold flower in the ratio 5:1:1.5, respectively) and essential oils of tea tree 1 % and geranium 1.5 %, purified water.

Conclusions. Based on organoleptic, physicochemical, rheological and microbiological studies, the composition of the ointment of complex action was developed based on active pharmaceutical ingredients of natural origin for the treatment of cheilitis of various etiologies.

Pharmaceutical providing of the treatment of children with epilepsy in Ukraine and abroad

Natalia Sholoiko, Liliia Hala, Kostyantyn Kosyachenko, Myroslava Hubar — Thu, 31 Aug 2023 00:00:00 +0300

The aim: to investigate the pharmaceutical providing for the treatment of epilepsy in children in Ukraine and abroad and to conduct a marketing analysis of the domestic market of antiepileptic drugs.

Materials and methods: Ukrainian and foreign Internet sources, medical and technological documents on a specific research topic, the regulatory and legal base of Ukraine, materials of the State Formulary of Medicines, the State Register of Medicines of Ukraine were the objects of the study. The methods of marketing analysis, graphic, documentary and analytical generalization were used.

Results: a comparative analysis of clinical protocols (France, Great Britain and Ukraine) for the treatment of epilepsy in children showed that there are only 12 INNs out of 37 INNs in the country. The analysis of the formulary lists of drugs of Great Britain and Ukraine showed that the BNFC has 32 INNs, and the domestic - 10 INNs. As of October 2022, 287 names of antiepileptic drugs are registered in Ukraine, and 164 of them are allowed in children's practice. The main producers of antiepileptic drugs are India and Ukraine. Children's drugs forms are mainly represented by tablets and capsules - more than 90%. A comparison of the lists of drugs for the treatment of epilepsy from the National List of Essential Medicines of Ukraine, BNFC, WHO Model List of Essential Medicines and WHO Model List of Essential Medicines for Children showed that out of 37 INNs, only 11 INNs are listed in all documents.

Conclusions: the results prove the need of improvement of pharmaceutical providing of epilepsy treatment in Ukraine. The nomenclature and variety of dosage forms for children's practice need to be expanded. In order to increase the economic availability of epilepsy treatment, it is advisable to update the National List of Essential Medicines of Ukraine and include new drugs in it, which will make it possible to purchase them at the expense of the State Budget of Ukraine

Study of the uroantiseptic activity of the complex of glycosides of phenolic compounds from lingonberry leaves in complex with the arginine amino acid

Thu, 31 Aug 2023 00:00:00 +0300

The aim of the work – study the uroantiseptic activity of a complex of glycosides of phenolic compounds from lingonberry leaves in a complex with the amino acid arginine.

Materials and methods. The object of the study was a phytosubstance, which is a complex of glycosides of phenolic compounds from lingonberry leaves in combination with the amino acid arginine (CGPA). Female laboratory rats were given a cleansing enema twice, after which the rats were provided with adequate sedation by injecting IV XYLA 2 % for anesthesia, then rectally injected 1000 μl of Escherichia coli strain at a concentration of 10⁹ CFU/ml. The next day after infection, the animals were subjected to cryogenic action - acute cold stress at a temperature of 0+2 °C for 2.5 hours, promoting the development of the infectious and inflammatory process. The uroantiseptic effect was studied according to the following parameters: the number of leukocytes in the urine, the number of colony-forming microorganisms E.coli in 1 ml of urine (CFU/ml).

Results. According to the obtained results of the experiment, it was established that the complex of glycosides of phenolic compounds from the leaves of lingonberry in a complex with the amino acid arginine (CGPA) showed a high uroantiseptic effect in the experimental treatment of urinary tract infection caused by E. coli ATCC 25922, which was manifested in the sanitation of the urinary tract from the uropathogen E. Coli.

Conclusions. Analyzing the results, it can be concluded that on the model of urinary tract infection against the background of cryogenic exposure, CGPA at a dose of 100 mg/kg showed a uroantiseptic effect, which was stronger than the comparison drug "Inurek" and contributed to a faster disappearance of the titer of colony-forming microorganisms in 1 ml of urine about 2 days earlier than in the group that received dietary supplements of herbal origin "Inurek" and the disappearance of leukocyturia 3 days earlier compared to the group that received therapy with the comparison drug "Inurek". The obtained results indicate the prospects of further research of CGPA with the aim of creating new effective uroantiseptic agents of plant origin based on it

In vitro evaluation of the antiglycation and antioxidant potential of the dietary supplement L-citrulline

Thu, 31 Aug 2023 00:00:00 +0300

Diabetes mellitus (DM) represents a significant global public health concern. It is a metabolic condition characterized by abnormal glucose levels in the bloodstream, known as hyperglycemia. This condition arises due to irregular insulin secretion, defective insulin receptivity, or a combination of both factors. The primary contributors to diabetic complications are protein glycation and oxidative stress resulting from chronic hyperglycemia.

The aim. The increasing incidence of diabetes mellitus has prompted a quest for a novel, cost-effective, and efficacious medication. The objective of the study generally intends to explore and investigate the antiglycation and antioxidant potential of the dietary supplement L-Citrulline

Materials and methods. A two-reaction model system was carried out to study and monitor the inhibitory impact of the dietary supplement L-Citrulline against advanced glycation end products (AGEs) formation. This system involved the in vitro glucose bovine serum albumin (BSA-glucose assay) and methylglyoxal bovine serum albumin (BSA-MGO assay). The antioxidant activity of the supplement was assessed by measuring its capacity to chelate metal ions and scavenge reactive oxygen species. The iron chelating activity was evaluated through absorbance measurements, while fluorescence measurements were employed for the remaining assays.

Results. According to the findings of the antiglycation assays, it was observed that the dietary supplement L-Citrulline demonstrated inhibitory properties against the development of advanced glycation end products (AGEs) in the BSA-Glucose model at a concentration of 100 ppm. The degree of inhibition with respect to glycation was ascertained to be 52.19 ± 0.39 % through observation. The BSA-MGO model has exhibited inhibitory properties with an observed activity of 49.64 ± 0.27 % at 100ppm concentration with respect to glycation. On the other hand, the supplement demonstrates antioxidant characteristics through the chelation of Fe ions, leading to a percentage difference in activity of 68.58 ± 0.45 % compared to the control at 100 ppm. The utilization of Glucolypotoxixity (GLT) media during the reactive oxygen species assay yielded a significant rise of 173.48 ± 9.37 % in the reactive species levels compared to the control, with statistical significance. The addition of 10 mM dietary supplement L-Citrulline resulted in a noteworthy reduction of 98.42 ± 5.04 % in the escalation. Therefore, it can be deduced that utilizing L-Citrulline as a dietary supplement exhibits potential for its therapeutic applications in eliminating reactive oxygen species (ROS) within skeletal muscle cells.

Conclusion. The study results suggest that the dietary supplement L-Citrulline has demonstrated inhibitory capabilities against glycation at varying concentration levels. Furthermore, it was noted to exhibit significant efficacy in both sets of antioxidant tests. Therefore, the supplement exhibits potential in the treatment of diabetes mellitus

Development of a new solution for determining the solubility limit of quercetin and other poorly soluble substances in aqueous solutions using the method for determining total organic carbon

Nataliia Khanina, Victoriya Georgiyants, Vadim Khanin — Thu, 31 Aug 2023 00:00:00 +0300

Aim. Given the incompleteness of literature data on the solubility of quercetin and the importance of this physicochemical characteristic in the study of its bioavailability, there is a need to develop an alternative method for accurately quantifying the solubility limit of quercetin.

Materials and methods. The concentration of quercetin in the samples was determined by directly determining the total organic carbon. For measurements, a total organic carbon analyzer 450 TOC (METTLER TOLEDO) was used with a range of measured values of 0.05–1000 ppbC µgC/l.

Results. The exact limit of the solubility of quercetin, as a poorly soluble substance, has been established. Having previously measured the value of total organic carbon in the prepared solutions, we obtained data on the concentration of quercetin in solutions depending on the pH of the solution.

Having built a graphical dependence of the measured values of the concentration of a substance on the pH values of the studied solutions, we obtain a mathematical equation of the reliance. Using the resulting function equation, one can approximate the concentration value of a substance with a pH value of 7.0. This value will be the solubility limit of the test substance for neutral media.

Conclusions. As a result of the research, a new method was proposed for the quantitative determination of the solubility limit of a substance, with an accuracy not exceeding 5.0 %. The method is based on measuring the concentration of total carbon in acidic solutions with different pH values and subsequent approximation of the obtained dependence of the pH value equal to 7.0

Application of statistical tools for the formulation and optimization of carvedilol mucoadhesive buccal films by using natural polymers

Leela Lakshmi Vajrala, Umashankar M S, Alagusundaram M — Thu, 31 Aug 2023 00:00:00 +0300

The aim and objective of this study was to create mucoadhesive buccal films that contained the multipurpose medical carvedilol, which has a variety of medicinal uses.

Materials and methods. The films were equipped using a solvent casting technique and concentrations of natural polymers, including Sweet basil, Lime Basil seeds and Purple basil mucilage. The influence of Carbopol 934 P, a selected natural polymer, was also investigated. The formulation variables were improved by the use of a factorial design of experiments and evaluated for their physico-chemical and in vitro evaluations.

Result. These evaluations provided crucial insights into the properties of the buccal films. To evaluate the release profile and release kinetics of carvedilol from the films, in vitro drug release experiments were carried out in a phosphate buffer solution. Ex vivo permeation tests using fresh sheep buccal mucosa were performed to evaluate the drug's permeation through the buccal membrane. Samples were taken at regular intervals, and a UV Spectrophotometer was used for analysis. With a polymer solution concentration at level "3," formulation run R20 showed the best optimized buccal formulation. This formulation shows promise for further in vivo research.

Conclusions. The results of this study offer important new evidence about the design and efficacy of mucoadhesive buccal films containing carvedilol. The optimization of formulation parameters and the assessment of physicochemical properties and drug release kinetics contribute to the progress of reproducible buccal films

Methodological approaches to assessing digital maturity of logistics activities of pharmaceutical enterprises

Thu, 31 Aug 2023 00:00:00 +0300

The aim: development of methodological approaches to assessing the digital maturity of the logistics activity of a pharmaceutical enterprise and elaboration of the proposed methodology on the example of those domestic enterprises that have a developed logistics system and some experience in the implementation of digital technologies in logistics activities.

Materials and methods: Research was conducted using databases on the Internet: the European Center for Information Systems Research, the European Medicines Agency, and scientific and metric databases - Scopus, Web of Science. Logical, systematic analysis and synthesis, graphic methods of research, and methods of mathematical and statistical analysis (expert, pair correlation and taxonomic) were used.

The results. An analysis of the state of implementation of digital technologies was carried out on the example of domestic pharmaceutical enterprises, which have been the leaders of the pharmaceutical market in recent years. It is substantiated that the assessment of digital maturity is a mandatory prerequisite for the digital transformation of pharmaceutical market entities. The existing models of digital maturity assessment are analyzed, and their shortcomings are identified. Based on this, a methodology for assessing the digital maturity of the logistics activities of pharmaceutical enterprises is proposed. An algorithm for the practical implementation of the methodology for assessing the digital maturity of the logistics activity of pharmaceutical enterprises is proposed. Based on the application of the proposed methodological approaches for assessing digital maturity using the taxonomic method, the calculation of the integral indicator of the level of digital maturity of the logistics activity of domestic pharmaceutical enterprises was carried out. The priorities for the implementation of digital technologies in the logistics activities of pharmaceutical enterprises were determined depending on the degree of their digital maturity.

Conclusions. It has been proven that the digital transformation of the logistics activities of pharmaceutical enterprises is a complex process that must consider many factors of the internal and external environment of the pharmaceutical enterprise. It is impossible to form a strategy and make decisions about investing in digital technologies without first assessing your real opportunities and weak points of the enterprise. That is why the assessment of the existing level of digital maturity is an important step on the way to the systematic digitalization of the logistics activities of a pharmaceutical enterprise. The proposed methodical approaches to assessing the digital maturity of the logistics activity of pharmaceutical enterprises will allow to form a holistic view of the real level of digital maturity of a certain enterprise and its deviation from the desired state, determine the priority directions for increasing the level of digital maturity, based on the specifics of the logistics activity of a particular pharmaceutical enterprise, and develop a sound digital strategy to improve the performance of both the individual business and the pharmaceutical supply chain

Chemical composition and antimicrobial activity of Rosa Damascena mill. (variety rainbow) from clonal micropropagation

Thu, 31 Aug 2023 00:00:00 +0300

Damask rose of the Veselka variety is an important industrial rose variety used to obtain essential oil. It is widely used in modern cosmetology, perfumery, and aromatherapy. In addition, the essential oil of Damask rose has a whole spectrum of pharmacological properties.

The scientific innovation of this research lies in its foundation on cultivating and acquiring planting materials of the Damask rose in vitro. This approach guarantees controlled conditions for plant growth, the production of robust seedlings, and an enhancement in the precision and credibility of the research outcomes.

Moreover, the study has scientific novelty in that it explores to assess both the quantitative and qualitative constituents of the essential oil in the acquired plant material of the Damask rose. This assessment takes place within the context of cultivating regenerative plants in an outdoor environment. Such an approach acknowledges the potential distinctions in the oil's component composition acquired from plants propagated through this method in comparison to traditional vegetative reproduction. Lastly, the research has scientific novelty in investigating the potential antimicrobial properties of Damask rose essential oil, which could have significant practical implications in the development of new drugs and combatting infectious diseases.

The purpose of the study was to establish the component composition of the essential oil of Rosa damascena Mill., which was grown in vitro, and to determine its antimicrobial effect.

Methods. The object of the study was the essential oil of Damask rose of the Veselka variety, which was grown by the method of clonal micropropagation in vitro. The essential oil was extracted from fresh petals collected during dry weather conditions prior to sunrise by hydrodistillation. Determination of the qualitative composition and quantitative content of volatile substances was carried out by the GC-MS method using an Agilent 7890B chromatograph. Antimicrobial activity was studied in vitro using the disk diffusion method with reference test strains of microorganisms Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Candida albicans ATCC 885-653.

Results. According to the results of the chromato-mass spectrometric study, 41 compounds (6 of which were in the isomeric state) were identified, which was belong to 13 different classes of chemicals. Dominant compounds among terpenoid substances were shown: geraniol – 30.96 %, citronellol – 27.08 %, alkanes: nonadecane – 17.29 %, and heneicosene – 5.46 %.

It was established that the essential oil of Damask rose had a significant antimicrobial effect against strains of C. albicans and E. coli, the diameters of which growth retardation zones ranged from 32-35 mm and 20-23 mm, respectively. In studies with P. aeruginosa and S. aureus, the essential oil showed moderate antibacterial activity: the diameters of the growth retardation zone of these microorganisms ranged from 13 to 15 mm and 11 to 12 mm, respectively.

Conclusion. For the first time, the qualitative composition and quantitative content of volatile substances in the essential oil extracted from the petals of Rosa damascena Mill., Veselka variety, cultivated through the clonal micropropagation in vitro, were explored by chromatography-mass spectrometry techniques. The results of the study of antimicrobial activity showed that the studied essential oil exhibits significant fungicidal effects against Candida microorganisms, along with moderate bactericidal effects on gram-negative (E. coli, P. aeruginosa) and gram-positive (S. Aureus) bacteria. These results highlight the potential of this essential oil for further investigation in the realm of developing novel medicines and herbal preparations. Further clinical studies are needed to assess this potential.

Study of pharmacological activity of dry extract of sakhalin willow shoots against the background of experimental thrombophlebitis

Liudmyla Maloshtan, Kateryna Artemova, Natalia Borodina, Oleksandr Kukhtenko — Thu, 31 Aug 2023 00:00:00 +0300

The aim. The objective of the research was to study the pharmacological activity of dry extract of Sakhalin willow shoots – DEWS against the background of experimental thrombophlebitis.

Materials and methods. Dry extract of Sakhalin willow shoots (DEWS) was the object matter of the present research and served as a therapeutic and prophylactic agent. In the experiment conducted, rabbits weighing 2.0 – 2.5 kg were used. The animals were divided into three groups. Group 1 was a control group; group 2 were animals that had been intragastrically injected with DEWS at a dose of 30 mg/kg prior to modelling thrombophlebitis; group 3 similarly received Eskuvit 20 mg/kg as a reference drug – pills (JSC Halychpharm, Ukraine). The dose for animals was recalculated, taking into account body weight according to the Rybolovlev method.

Experimental thrombophlebitis was caused by injecting an intravenous solution of 2 % lugol at a dose of 0.1 ml into the marginal vein of the ear. Statistical data processing was carried out using the Statistica for Windows 11.0 program based on variance analysis for repeated measurement data using the Mann-Whitney criteria at a probability level of p<0.05.

Results. Against the background of the development of experimental thrombophlebitis in rabbits, the development of thrombosis of the ear vein and the inflammatory process of adjacent tissues were observed. The inflammatory process was accompanied by pronounced hyperemia and oedema. Prophylactic administration of DEWS for 6 days contributed to a decrease in the inflammatory process already on the 5th day of observation. The area of the injured area was 20 % smaller than in the control pathology group. The therapeutic and prophylactic effect of herbal medicine can be explained by the content of flavonoids and salicylates in its composition. Eskuvit showed a less pronounced thrombolytic effect in terms of its influence on thrombosis and thrombolysis.

Conclusions. The administration of DEWS in the therapeutic and prophylactic regimen at a dose of 30 mg/kg has a pronounced anti-inflammatory, thrombolytic and venoprotective effect in experimental peripheral venous thrombophlebitis in rabbits. The results of the studies obtained allow us to recommend DEWS as a promising venoprotective agent with thrombolytic activity

Substantiation of creation of transdermal forms of drug delivery with antihypertensive action

Tatyana Shyteyeva, Elena Bezchasnyuk, Oleg Kryskiv, Vasyl Grynenko — Fri, 18 Aug 2023 00:00:00 +0300

The article presents the theoretical justification for the choice of active pharmaceutical ingredients of antihypertensive action for the creation of new forms of delivery - transdermal therapeutic systems.

Purpose: monitoring of studies on the use of angiotensin-converting enzyme (ACE) inhibitors in the development of transdermal drugs for the treatment of hypertension.

Materials: open access electronic resources of scientific periodicals from around the world: Google Scholar (https://scholar.google.com/); PubMed (https://pubmed.ncbi.nlm.nih.gov/); Sciencedirect (https://www.sciencedirect.com/); Pubchem (https://pubchem.ncbi.nlm.nih.gov/); National Library of Ukraine named after V. I. Vernadskyi (http://www.nbuv.gov.ua/); Ukrainian Institute of Intellectual Property (Ukrpatent) (https://sis.ukrpatent.org/uk/); Industrial Property (https://base.uipv.org/searchBul/); USPTO. The United States Patent and Trademark Office (https://www.uspto.gov/patents/search); European Patent Office (EPO) (https://www.epo.org/).

Methods of the research: information search, theoretical analysis and systematization of data from scientific sources, logical analysis.

Results: a review of scientific sources was carried out, and an analysis of ACE inhibitors as candidates for the creation of transdermal forms for the treatment of arterial hypertension was carried out. The pharmacological and physicochemical aspects of the possibility of their use for introduction through the skin are defined. It has been established that the search and development of the latest means of treatment of arterial hypertension, which would significantly increase the duration and quality of life of patients, are extremely relevant. Transdermal drug delivery systems are one of the pharmaceutical products being developed on the world market, and their use allows overcoming the associated disadvantages of other delivery routes.

Conclusions: the review of domestic and foreign literature confirmed the relevance of biopharmaceutical research in the field of development of innovative dosage forms - transdermal therapeutic systems for the treatment of hypertension.

The choice of promising antihypertensive active pharmaceutical ingredients of the ACE group (enalapril maleate, lisinopril dihydrate, and captopril) is substantiated, taking into account their specific physicochemical properties that are suitable for penetration through the skin.

The market for transdermal drug delivery is increasing, and there is a prospect of higher growth rates in this market in the coming years