ScienceRise: Pharmaceutical Science

Ecological optimization of synthesis routes for a new non covalent inhibitor of SARS CoV 2 main protease as a promising active pharmaceutical ingredient

Mon, 17 Nov 2025 00:00:00 +0200

When transitioning from laboratory synthesis to industrial production, comprehensive research involves more than just assessing quality and biological activity. A crucial aspect of developing a new active pharmaceutical ingredient (API) is the research and optimization of synthetic routes. This process must consider safety, environmental impact, and other parameters set by regulatory requirements.

In previous studies, we synthesized a new biologically active substance intended as a non-covalent inhibitor of the main protease of the SARS-CoV-2 virus [1]. In this work, we analyzed and quantitatively assessed the environmental characteristics of the synthetic routes and optimized the synthesis method for further scaling of the technology. To identify the key factors affecting the environmental impact and efficiency of the process, we applied the fundamental principles of “green chemistry”.

The aim of the study is to evaluate and optimize the environmental parameters involved in the synthesis of a new biologically active molecule: 1-(2-oxo-2-((pyridin-2-ylmethyl)(thieno[3,2-b]thiophene-2-ylmethyl)amino)ethyl)-5-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazole-4-carboxylic acid (HIT) [1]. This compound has shown promise as a non-covalent inhibitor of SARS-CoV-2 proteases for potential treatment of COVID-19. The optimization process aims to enhance the synthesis efficiency while also improving the environmental aspects, considering the future scalability of production.

Materials and methods. The study used computational methods, statistical and structural-logical methods, and the EcoScale and DataWarrior software tools.

Results. While studying synthetic routes, alternative solvents were considered, the number of stages was reduced, and the intensity of the process mass was improved.

Conclusions. A comprehensive approach to optimizing synthetic pathways has made it possible to improve the environmental parameters of the target molecule (HIT) synthesis scheme, increase the overall efficiency of the process, and develop safer and more efficient processes for scaling up and producing a new pharmaceutical substance

Acetylcholinesterase-targeted biogenic–thienopyrimidine hybrids: design, synthesis and pharmacological evaluation of compounds with anti-amnestic, anxiolytic-like and pain-modulating properties

Tue, 30 Dec 2025 00:00:00 +0200

The aim. To carry out the rational design, synthesis, and experimental evaluation of new glycine-linked thieno[2,3-d]pyrimidine hybrids as potential modulators of memory, anxiety, and pain for further correction of neurodegenerative processes, integrating in silico and in vivo investigations.

Materials and Methods. Organic synthesis methods; structure confirmation by ¹H, ¹³C NMR spectroscopy, LC-MS, and elemental analysis. Molecular docking was performed using AutoDock Vina, AutoDockTools 1.5.6, and Discovery Studio Client. The pharmacological studies were carried out using a scopolamine-induced amnesia model and included the following behavioral assays: the Passive Avoidance Test, the Light-dark Transition Test, the Rotarod Test, and the Hot Plate Test.

Results and Discussion. A series of newly designed glycine-linked thieno[2,3-d]pyrimidine hybrids was rationally developed, synthesized, and evaluated as potential modulators of neurodegenerative processes. The synthetic procedures for obtaining the intermediates and target 5-methylthieno[2,3-d]pyrimidin-4(3H)-one hybrids via amide coupling were optimized. Molecular docking to AChE (PDB ID: 7E3H) revealed that several derivatives, particularly 4d, 4f, and 4g, exhibited favorable binding energies (down to –12.5 kcal/mol) and formed an extensive network of hydrogen-bonding, halogen, π–π, and hydrophobic interactions within the active site of acetylcholinesterase. In vivo studies using the scopolamine-induced amnesia model demonstrated that these compounds display moderate anti-amnestic (pro-cognitive) properties and do not influence motor coordination or nociceptive sensitivity. Compound 4g showed anti-amnestic activity comparable to that of Donepezil, as well as pronounced anxiolytic effects. A correlation between the in silico predictions and the in vivo findings was established.

Conclusions. The rational design, synthesis, and structural characterization of new AChE-targeted inhibitors, combined with in silico calculations and subsequent in vivo validation, enabled the identification of several thieno[2,3-d]pyrimidine derivatives with moderate anti-amnestic properties in the scopolamine-induced amnesia model, highlighting their potential as promising structures for further optimization

Study of ascorbic acid in commercially available edible berries, fruits, and vegetables

Tue, 30 Dec 2025 00:00:00 +0200

Vitamin C, or ascorbic acid, is among the most essential and widely recognized compounds required for the healthy functioning of the human body. Consequently, vitamin C must be obtained through dietary sources or supplementation. Rich sources of ascorbic acid include a variety of fresh fruits and vegetables. It is advisable to investigate the content of ascorbic acid in the most common commercially available edible berries, fruits, and vegetables using the European Pharmacopoeia HPLC method.

The aim. The aim of this study is to perform a comparative analysis of the ascorbic acid content in commercially available edible berries, fruits, and vegetables on the Estonian market using the European Pharmacopoeia's HPLC method, and to identify the products richest in this vitamin. Such findings will enhance the knowledge of both consumers and researchers regarding the most promising dietary sources of vitamin C.

Materials and methods. Fifty-three samples of berries, fruits, and vegetables commercially available on the Estonian market have been studied. Quantitative analysis of ascorbic acid was performed using the HPLC method.

Results. This study evaluated the ascorbic acid content of commercially available and home-grown berries, fruits, and vegetables in Estonia. The highest levels were found in blackcurrants (70.6 ± 7 mg/100 g in garden samples and 53.3 ± 5 mg/100 g in market samples) and Sea buckthorn fruits (49 ± 6 mg/100 g (garden) and 43.8 ± 2 mg/100 g (market)). In general, home-grown berries and fruits were richer in ascorbic acid. Supermarket produce generally contained lower levels, although mandarins (24 mg/100 g) and red pepper (48 mg/100 g) were the richest sources. The study also demonstrated that the addition of dithiothreitol (DTT) makes the analytical results more informative. The experimental data obtained provide an overview and allow the ranking of commercially available edible berries, fruits, and vegetables according to their ascorbic acid content.

Conclusions. A comparative analysis of ascorbic acid content in 53 berries, fruits, and vegetables from the Estonian market was conducted using the European Pharmacopoeia's HPLC method. The richest dietary sources of vitamin C have been identified, providing valuable insights for both consumers and researchers and supporting rational approaches to nutrition and dietetics

Study of thermogravimetric profile of a mixture of diclofenac sodium and para-aminobenzoic acid as a basis for pharmaceutical development

Tue, 30 Dec 2025 00:00:00 +0200

In modern conditions, in particular, against the background of an increase in the frequency of traumatic injuries to the organs of vision because of hostilities and the influence of professional factors, the development of new ophthalmic dosage forms is of particular relevance. Combined drugs containing several active pharmaceutical ingredients, in particular diclofenac sodium and para-aminobenzoic acid, are considered promising solutions for the treatment of infectious and inflammatory eye lesions. At the same time, the effectiveness and safety of such combinations directly depend on their physicochemical compatibility, which determines the stability of the finished dosage form.

The aim of the study is to investigate the thermal stability and possible physicochemical interactions between diclofenac sodium and para-aminobenzoic acid by derivatographic analysis of individual substances and their mixture in a 1:1 ratio.

Materials and methods. The objects of the study were the pharmaceutical substances diclofenac sodium, para-aminobenzoic acid and a model mixture of the specified active pharmaceutical ingredients. Thermogravimetric analysis was carried out on a Shimadzu DTG-60 device in thermogravimetric analysis and differential thermal analysis modes in the temperature range of 17–250 °C with a heating rate of 10 °C/min in an air atmosphere.

Results. In the process of thermogravimetric research, it was established that diclofenac sodium is characterized by high thermal stability. Para-aminobenzoic acid showed three stages of thermal destruction, but analysis of the mixture in a 1:1 ratio did not reveal the appearance of new thermal effects or shifts in the degradation profiles.

Conclusions. The results of thermogravimetric analysis indicate the compatibility of diclofenac sodium and para-aminobenzoic acid in terms of thermal characteristics, which confirms the prospects of their simultaneous use

Effects of noni leaf extract (Morinda citrifolia L.) on the histopathological appearance of mouse aorta

Tue, 30 Dec 2025 00:00:00 +0200

Hypercholesterolemia is a metabolic disorder that can lead to the formation of atherosclerotic plaques. One method to manage atherosclerosis is by lowering cholesterol levels. Cholesterol reduction can be achieved through the use of medications or medicinal plants. One of the plants that can be used to lower levels is the noni leaf (Morinda citrifolia L.).

The aim. The aim of this study is to investigate the histopathological changes in the aorta of mice after treatment with noni leaf extract.

Materian and methods. This study was conducted using 25 male mice aged 2-2.5 months with a body weight of 25-30 grams, divided into 5 treatment groups, each consisting of 5 mice. The first group was left untreated as the normal control (KN). The second group was given 0.5% CMC-Na at a dose of 0.28 ml/20 g body weight as the negative control (K(-)). The third group received simvastatin at a dose of 0.026 mg/20 g body weight as the positive control (K(+)). The fourth (P1) and fifth (P2) groups were administered noni leaf extract at doses of 5.6 mg/20 g body weight and 11.2 mg/20 g body weight, respectively.

Result. The results of the study indicate that the histopathological findings of the mouse aorta in each treatment group are consistent with the average damage scores obtained for each group. The histopathological findings of the aorta in the normal control, negative control, positive control, extract dose 1, and extract dose 2 groups showed average damage scores of 0.00, 0.20, 1.40, 0.53, and 0.27, respectively.

Conclusion. It can be concluded that the noni leaf extract at doses of 5.6 mg/20 g body weight and 11.2 mg/20 g body weight can improve, reduce, and diminish the histopathological damage to the mouse aorta, although not as effectively as simvastatin at 0.026 mg/20 g body weight

Development and validation of an HPLC method for the determination of glucosamine hydrochloride in a medicinal product in the form of a cream

Nataliia Bevz, Yaroslav Studenyak, Olena Ivaniuk, Olena Ruban — Thu, 18 Dec 2025 00:00:00 +0200

The development of medicinal products requires the use of selective and reproducible analytical methods that ensure reliable determination of active ingredients. The analysis of glucosamine hydrochloride as a medicinal product in the form of a cream has specific challenges due to its high polarity and lack of a chromophore; therefore, its determination within the dosage form requires a specially adapted analytical approach.

The aim. To develop and validate a liquid chromatographic method for the determination of glucosamine hydrochloride in a medicinal product in the form of a cream in accordance with the requirements of ICH Q2(R2), the State Pharmacopoeia of Ukraine (SPhU), and the European Pharmacopoeia (EP).

Materials and methods. The object of the study was an experimental batch of a cream containing glucosamine hydrochloride (1%). The analysis was performed using a KNAUER Smartline chromatograph equipped with a UV detector and a Zorbax SB-C8 column (150 × 4.6 mm, 5 μm). Phenyl isothiocyanate was used for derivatization, resulting in the formation of a UV-active glucosamine derivative. Validation was carried out with respect to specificity, linearity, accuracy, precision, system suitability, and robustness.

Results. Optimal chromatographic conditions were established (mobile phase: acetonitrile–water, 40:60, acidified with phosphoric acid to pH 3.0; detection wavelength 230 nm; flow rate 1.0 mL/min; column thermostat temperature 25°C), ensuring complete separation of the glucosamine derivative (retention time 2.21 min) from sodium benzoate (retention time 3.55 min) and other excipients in the cream formulation. The minimum required concentration of the derivatization reagent was determined to be 0.008–0.01 g/mL. Evaluation of validation parameters confirmed the specificity of the method, its linearity within the 80–120% range (r = 0.9991), precision (ΔZ = 0.61%), accuracy (δ = 0.31%), repeatability (≤ 2%), and robustness (analytical solutions stable for 1 hour). Metrological assessment (n = 6) demonstrated that the systematic error was statistically insignificant, while the relative uncertainty of a single determination was 7.88% at a confidence level of P = 0.95. The detection limit of glucosamine hydrochloride is 0.23 μg/ml.

Conclusions. An HPLC method for the determination of glucosamine hydrochloride in a cream formulation after derivatization with phenyl isothiocyanate has been proposed and experimentally substantiated. The method complies with the requirements of international guidelines and can be applied in quality control for the identification and quantitative determination of the active pharmaceutical ingredient in the investigated medicinal product

Research on the optimization of the composition and technology of combined tablets of bisoprolol fumarate with indapamide

Nadia Malanchuk, Demchuk Demchuk — Tue, 30 Dec 2025 00:00:00 +0200

The aim. The study was focused on the development and optimization of a rational tablet formulation containing bisoprolol fumarate and indapamide by applying a response surface methodology to ensure the required pharmaco-technological and biopharmaceutical characteristics of the final dosage form.

Materials and methods. The central composite design was used to establish the relation between independent variables, such as, quantity of PEG 6000, quantity of Prosolv EASYtab SP, quantity of Sachelac 80 and dependent variables, such as flowability, bulk density, tapped density, angle of repose, Carr’s index, uniformity of weight, friability, tablet hardness and disintegration time in order to obtain the optimal formulation using response surface methodology. Tablets were prepared by direct compression method. Quantitative determination of APIs in tablets was quantified by HPLC with UV detection at 220 nm.

Results. After generating the polynomial equations that relate the dependent and independent variables, the process was optimized for five responses. It was found that the tablet contained 1% PEG 6000, 37% Prosolv EASYtab SP, and 37% Sachelac 80 was a better formulation in terms of hardness (89 N), uniformity of weight (1.1%), friability (0.20%) and rapid disintegration (2.3 min). The experimental values of the dissolution of optimized tablets showed 95.6% release of bisoprolol fumarate and 99.7% release of indapamide. The quantitative content of active ingredients (bisoprolol fumarate and indapamide) in the developed tablets meets the requirements of the State Pharmacopoeia of Ukraine.

Conclusions. The study enabled the development of an optimized formulation and manufacturing process for combined bisoprolol fumarate and indapamide tablets, ensuring compliance with pharmaco-technological standards and demonstrating the applicability of response surface methodology for formulation design

Current state of scientific research on pharmacological correction of mammary gland pathologies (a scoping review)

Tue, 30 Dec 2025 00:00:00 +0200

The aim of the study is to conduct a bibliosemantic analysis of scientific literature on pharmacological correction of breast pathologies and to determine the proportion of studies on pharmacological correction of mastopathy.

Materials and methods. In the context of our study, the analysis of data on the current state of research on the pharmacological correction of mammary gland pathologies and the identification of the proportion of studies focusing on the pharmacological correction of mastopathy was carried out using the enhanced Arksey & O’Malley methodology proposed by a group of researchers led by H.M. Daudt. A total of 540 publications (from the last five years) were reviewed.

Results. The results of the study showed that the vast majority of publications are devoted to the pharmacological correction of breast cancer (78%). Studies on the pharmacological correction of mastopathy make up a significantly smaller share (22%), which confirms their relevance, particularly regarding the development of original drugs. Among these, herbal-based medicinal products are most commonly used as part of combination therapy (59%).

Conclusions. Studying the current state of scientific research on a given topic is an integral part of planning and developing a strategy for one's own research. A detailed analysis of the available literature makes it possible to identify unresolved issues that remain unaddressed by researchers from different countries, and to outline relevant niches for further scientific investigation.

A bibliosemantic analysis of scientific literature on pharmacological correction of breast pathologies was conducted, and the relevance of conducting research on the development of herbal remedies for the pharmacological correction of mastopathy was established.

The effect of tablets containing dry extract of peony roots, L-tryptophan, and glycine on the condition of the brain in the context of experimental cranio-cerebral trauma

Nadiia Kononenko, Ruslan Mirzaliiev — Tue, 30 Dec 2025 00:00:00 +0200

The aim of this work was to experimentally substantiate the neuroprotective potential of new combined tablets containing dry extract of peony roots, L-tryptophan, and glycine to eliminate the existing gap in the pharmacotherapy of traumatic brain injury (TBI) associated with the insufficient effectiveness of current monotherapeutic approaches.

Material and methods. The study was conducted on 40 male white rats weighing 200–250 g. The TBI model was induced by the free fall of a weight onto a fixed head of the animal. The test preparation was administered orally for 7 days. The effectiveness was assessed using morphological, morphometric, and biochemical methods, including the determination of neuron-specific enolase (NSE) and S100 protein levels in blood serum, as well as analysis of the condition of neurons in the sensorimotor cortex and hippocampus.

Results. Rats with TBI demonstrated a significant increase in NSE and S100 levels, a decrease in the number of normochromic neurons, activation of glial cells, and cerebral tissue oedema. Administration of the combined drug contributed to a reduction in neuronal damage markers, a decrease in the glio-neuronal index, and normalization of brain microstructures. Morphological examination revealed preservation of the neuronal layer and a reduction in destructive changes, indicating a pronounced neuroprotective effect of the drug.

Conclusions. The developed combined drug demonstrated an effective protective effect on brain tissue under conditions of experimental TBI. The obtained results substantiate the feasibility of further preclinical studies to investigate its mechanisms of action and potential clinical application

Analysis of state macroeconomic indicators of healthcare systems development in reference countries for the domestic pharmaceutical market

Tue, 30 Dec 2025 00:00:00 +0200

Regulation of drug availability is one of the most important areas of state policy in the pharmaceutical market. The use of various methods of price regulation allows achieving the desired socio-economic results, but the complexity of the processes taking place in the pharmaceutical market and in the state necessitates the constant revision of existing approaches and measures.

The aim: to conduct an analysis of macroeconomic indicators characterizing the state of development of healthcare systems in countries that are reference for the domestic pharmaceutical market.

Materials and methods. General theoretical (historical, formal, graphical, hypothetical-deductive, etc.) and applied (organizational-economic, mathematical-statistical, etc.) research methods were used. The subject of the research was the World Bank health indicators, which are integrated with WHO data, and data from the Organization for Economic Cooperation and Development for reference countries (Poland, Slovakia, the Czech Republic, Latvia, Hungary, Romania, Moldova, Bulgaria) and in Ukraine.

Results. It was found that for the vast majority of indicators characterizing the state of health care financing, domestic indicators significantly differed from the average values for the group of reference countries. For indicators of domestic health care expenditures (four indicators), domestic data had critically low values (52.12% –% in current healthcare spending, expenditures per capita, including at purchasing power parity of the population – $ 192.81 and $ 570.60, respectively). Only for the indicator of domestic public health care expenditures as a% of general government expenditures, Ukrainian indicators (10.56%) were within the fluctuation range of the corresponding data for the group of reference countries. A comparative analysis of current healthcare expenditures (3 indicators) showed that out of the three indicators, the values of two in Ukraine were close to the minimum values in the group of reference countries. These are current healthcare expenditures per capita, including at purchasing power parity. In Ukraine, the values of these indicators were $369.90 and $1095.06, which were 3.72 and 2.49 times lower than the average values for the group of reference countries. According to the indicators characterizing the participation of private capital and citizens in healthcare expenditures (5 indicators), it was established that per capita private expenditures in Ukraine were $177.10, which was 1.88 times lower than the average for the group of reference countries ($332.58). In terms of private and out-of-pocket expenditures as a% of current healthcare expenditures, domestic data had the highest values compared to reference countries. Thus, private and out-of-pocket expenditures in Ukraine were 1.76 and 1.88 times higher than the average values for reference countries (27.07% and 24.04%, respectively). Domestic out-of-pocket expenditures calculated per capita ($167.54) and at purchasing power parity ($ 495.88) were 44,49% and 17,51% lower than the corresponding average values for the group of reference countries ($301.82 and $ 601.10, respectively). It was found that within the group of reference countries, the drug consumption index varied. This index ranged from $523.0 (Poland) to $883.0 (Bulgaria). The average consumption value in Ukraine for 2021-2023 was ($112.33), which was 5.79 times less than the corresponding data for the group of reference countries. In addition, in the group of reference countries, there are fundamental differences in the structure of population spending on medicines by funding sources (state, private revenues, and health insurance funds).

Conclusions. Significant differences in macroeconomic indicators characterizing the state of healthcare financing in the reference countries and in Ukraine have been identified. This necessitates further research on the topic and a review of the group of reference countries used in the domestic pharmaceutical market to regulate the socio-economic accessibility of medicines for the population