rss_2.0European Pharmaceutical Journal FeedSciendo RSS Feed for European Pharmaceutical Journal Pharmaceutical Journal Feed Cleavage and Cytotoxic Activity of Copper(II) Complexes Based on Reduced Schiff Bases Derived From Salicylaldehyde and Amino Acids<abstract> <title style='display:none'>Abstract</title> <p>Metal complexes, which, under physiologic conditions, show redox properties and are able to bind to DNA, are great tools to cleave the DNA chain. This aspect is of great importance for their use as antineoplastic drugs. We synthesized ligands derived from short-chain amino acids and from salicylaldehyde. The prepared ligands of the type of reduced Schiff bases were subsequently used for the preparation of copper(II) complexes. The aim of the study was in vitro testing of copper(II) complexes, where it was confirmed that they are capable of cleaving DNA. Their cytotoxic activity was also confirmed by the resazurin redox method on Saccharomyces cerevisiae based on preserved healthy mitochondrial function.</p> </abstract>ARTICLEtrue Mushrooms Cordyceps as a New Source of Bioactive Compounds and Their Complexation With Silver Ions<abstract> <title style='display:none'>Abstract</title> <p>Mushrooms from the genus <italic>Cordyceps</italic> are characterized by a wide range of biological effects due to the diverse amount of substances contained in them and are an important source of bioactive compounds. In China, mushrooms of the genus <italic>Cordyceps</italic> have been used as a medicinal preparation of traditional Chinese medicine for centuries. So far, a considerable number of studies have been conducted that focused on analyzing the effects of <italic>Cordyceps</italic>, which include their antioxidant, antibacterial, immunomodulatory, antidiabetic, antitumor, and many other effects. The ability of fungi to form complexes with various metals is also interesting. It is believed that polysaccharides are the main component of the extracts involved in the complexation with metals, after which their biological effects are improved and deepened. The work deals with the comparison of the antioxidant and antibacterial effects of <italic>Cordyceps</italic> extracts with extracts of this mushroom enriched with silver ions. Based on scientific studies, it is assumed that there is a complexation between the chemical compounds of the extracts and silver.</p> </abstract>ARTICLEtrue N as a potential drug target<abstract> <title style='display:none'>Abstract</title> <p>Aminopeptidase N (APN) is a broad specificity zinc metallopeptidase with many functions that do not always depend on its enzymatic activity. Among others, it is involved in tumor angiogenesis and metastasizing and also serves as a cellular receptor of some coronaviruses. Some APN inhibitors, such as bestatin or tosedostat, were used or tested as anticancer drugs in the past. Within the past two decades, we have prepared several series of potential APN inhibitors. Some of them reached interesting values of inhibitory activity and were also successfully tested for antiproliferation activity in cancer cell lines. We also performed some QSAR studies with APN inhibitors prepared by us and other authors.</p> </abstract>ARTICLEtrue of Abstracts 51st Conference Synthesis and Analysis of Drugs (SAD 2023) Oral Presentations of Abstracts 51 Conference Synthesis and Analysis of Drugs (SAD 2023) Poster Session Acid in Underground Parts of Different Species<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Mints (<italic>Mentha</italic> L., Lamiaceae) are medicinal plants frequently used in pharmacy, cosmetics, and food industry. Among the secondary metabolites found in mint, rosmarinic acid is one of the most abundant in the whole plant. Rosmarinic acid is known as a powerful antioxidant and anti-inflammatory agent.</p> </sec> <sec><title style='display:none'>Aim</title> <p>There is much information about the use and profile of secondary metabolites of mint's aerial parts. On the contrary, less is known about the secondary metabolites in the rhizomes. So, this research intended to determine the content of rosmarinic acid in the underground parts of 10 species of the genus <italic>Mentha</italic>, section <italic>Mentha</italic>.</p> </sec> <sec><title style='display:none'>Method</title> <p>High-performance liquid chromatography with diode array detection (HPLC-DAD) was used to identify and determine rosmarinic acid.</p> </sec> <sec><title style='display:none'>Results</title> <p>Rosmarinic acid was detected in all 10 species. The highest amount was found in <italic>Mentha × piperita</italic> L. “BULHARSKA 1” and <italic>Mentha rotundifolia</italic> (L.) Huds. The lowest content of rosmarinic acid was found in <italic>Mentha arvensis</italic> L., and a slightly higher content was measured in <italic>Mentha × piperita</italic> L.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>The underground parts of mints seem to be an interesting source of natural antioxidants such as rosmarinic acid.</p> </sec> </abstract>ARTICLEtrue Conference Synthesis and Analysis of Drugs (SAD 2023) of taurine in soft drinks by an ultrahigh-performance liquid chromatography-mass spectrometry method<abstract> <title style='display:none'>Abstract</title> <p>Taurine (2-aminoethanesulfonic acid) is a free sulfur-containing β-amino acid widely distributed in many mammalians. Owing to the energizing effects, it is mostly used in soft drinks and supplements for athletes. Regular intake of soft drinks may lead to an overdose of caffeine, taurine, and guarana and loss of bone mass, overweight, hypertension, and in older age, osteoporosis and cardiovascular diseases. Therefore, it is essential to control the maximum amount of taurine consumed by humans in the food and beverages. Here, a fast, simple, accurate, and robust method based on ultrahigh-performance liquid chromatography hyphenated with mass spectrometry (UHPLC-MS) was successfully applied for the determination of taurine in selected soft drinks sold in Slovakia. The method was characterized by coefficient of determination higher than 0.99, and the predicted value of the limit of detection was 4.29 μmol/L. The analyzed levels of taurine in selected commercial drinks ranged from 2.8 to 3.78 mg/mL. The concentration in one brand of the investigated drinks was found to be extremely low (about 70%) compared to the declared content by the manufacturer.</p> </abstract>ARTICLEtrue Randomized, Two-Treatments, Two-Periods, Crossover, Open label, Laboratory-Blind, Single Dose Bioequivalence Study between Vildagliptin/Metformin 50 mg/1000 mg Film Coated Tablets (Sensityn) and Galvusmet 50 mg/1000 mg Film Coated Tablets in healthy adults under fed conditions<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Aim</title> <p>Vildagliptin/metformin 50 mg/1000 mg film coated tablets (Sensityn<sup>®</sup>) is being developed for the treatment of type 2 diabetes mellitus. An open label, crossover, bioequivalence study (phase I) was conducted to assess the bioequivalence between Sensityn<sup>®</sup> Film Coated Tablets (Test Product/Alpha Pharma Industries, a subsidiary of Cigalah Healthcare LLC, KAEC, Saudi Arabia) and Galvusmet<sup>®</sup> Film Coated Tablets (Reference product/Novartis Pharma, Switzerland), in healthy adults under fed conditions. Safety and tolerance were evaluated as secondary endpoints.</p> </sec> <sec><title style='display:none'>Materials and methods</title> <p>A randomized study with two treatments, two periods, crossover, open-label, laboratory-blind, single dose, with a washout period of seven days under fed conditions in 36 healthy male subjects. These were administered medicinal drug product (Sensityn<sup>®</sup>) or the reference medicinal product (Galvusmet<sup>®</sup>); both as a single 50 mg/1000 mg oral dose, under fed conditions. Blood samples were collected for pharmacokinetic analysis before treatment and until 24.00h post-dosing in each study period. ANOVA analysis (test sequence, subjects’ nested within sequence, product and period effect) was performed using a 5% significance level for logarithmic and untransformed data for C<sub>max</sub> AUC<sub>0-t</sub> and AUC<sub>0-∞</sub> and for untransformed data for T<sub>max</sub>, K<sub>elimination</sub> (λz) and half-life.</p> </sec> <sec><title style='display:none'>Results</title> <p>The results showed that C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-∞</sub> have passed the 90% CI acceptance limits of 80.00%–125.00% for vildagliptin and metformin. Consequently, the bioequivalence of Sensityn<sup>®</sup> and Galvusmet<sup>®</sup> film coated tablets was demonstrated under fed conditions. Treatment emergent adverse events were reported by 3 subjects and 1 subject following the administration of Sensityn<sup>®</sup> and the Galvusmet<sup>®</sup>, respectively.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>The present findings confirmed that Sensityn<sup>®</sup>, the test medicinal product is bioequivalent to Galvusmet<sup>®</sup>, the reference medicinal product, in the rate and extent of absorption. Also, it has comparable safety profile. These findings support the continued development of vildagliptin/metformin 50 mg/1000 mg film coated tablets (Sensityn<sup>®</sup>) for use in patients with type 2 diabetes mellitus.</p> </sec> </abstract>ARTICLEtrue and Evaluation of Gastroretentive Gelling System of Ketoprofen<abstract> <title style='display:none'>Abstract</title> <p>A revolutionary concept for achieving long-term medication release is the gastroretentive <italic>in situ</italic> gelling system. The goal of this research was to formulate and test a gastroretentive <italic>in situ</italic> gel for ketoprofen delivery to targeted site to increase the residence and delivery time. Ketoprofen gastroretentive <italic>in situ</italic> gels were synthesized using a cation-driven gelation approach using various combinations and concentrations of polymers such as gellan gum, sodium alginate, and hydroxypropyl methylcellulose (HPMC) K100M. Visual appearance, pH, viscosity, <italic>in vitro</italic> gelation, <italic>in vitro</italic> buoyancy, drug content, density measurement, gel strength measurement, water uptake, and <italic>in vitro</italic> drug release were all evaluated. The total floating time was more than 12 h, with a floating lag time of less than 2 min. The formulations showed pH ranging from 6.89 to 7.61 and drug content ranging from 82.01% to 95.53%. For 11 h, the percent cumulative drug release of formulations F5 and F14, which contained a greater concentration of polymer sodium alginate (1.5%) and a combination of gellan gum and HPMC K100M (0.175% and 0.2%), was 84.10% and 85.49%, respectively. <italic>In vitro</italic> dissolution experiments and stability investigations both revealed no significant changes in drug content. The findings revealed that the formulated <italic>in situ</italic> gels aided in extending gastric residence duration, allowing the drug to be released in the stomach.</p> </abstract>ARTICLEtrue of raloxifene in the management of postmenopausal osteoporosis of rheumatoid arthritis patients<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Objective</title> <p>Due to the severe side effects of long-term treatment using hormone replacement therapy, Raloxifene (RLX) is introduced with beneficial effects on rheumatoid arthritis (RA) for postmenopausal women. This review was conducted to collect data from the available literature on RLX for the management of postmenopausal women suffering from RA.</p> </sec> <sec><title style='display:none'>Method</title> <p>All studies published up to 2019 were searched in four databases, including Google Scholar, PubMed, Scopus, and Medline. All articles were searched using several keywords, including “Raloxifene” or “Evista” in combination with “Rheumatoid Arthritis” or “Autoimmunity”. Finally, six studies were selected for the review analysis of this study. In all studies, 60 mg/day RLX was administered for postmenopausal subjects. The majority of the studies showed that the use of RLX was effective in postmenopausal women who underwent corticosteroid therapy. No severe complications were reported after RLX therapy in patients with RA.</p> </sec> <sec><title style='display:none'>Result</title> <p>Based on the obtained results, RLX is a selective estrogen receptor modulator that its short-term anti-arthritic effects are proven in the treatment of postmenopausal osteoporosis. It was well tolerated without serious adverse events.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>It seems that RLX is a promising treatment candidate in postmenopausal RA due to its anti-arthritic and anti-osteoporotic effects and based on the outcomes of experimental postmenopausal arthritis in animal and human studies.</p> </sec> </abstract>ARTICLEtrue evaluation of the nonselective and selective TMEM16 family calcium-activated chloride channel blockers in the airways<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>The family of calcium-activated chloride channels, TMEM16, plays a significant role in contributing to the pathogenesis of airway inflammatory diseases. Targeting these ion channels and aiming to modulate them may provide an interesting new approach to the therapy of these potentially fatal diseases.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We tested this hypothesis in both healthy and ovalbumin (OVA)-sensitized male Dunkin-Hartley guinea pigs. The ion channel activity was modulated by TMEM16A-nonselective (benzbromarone) and TMEM16A-selective blockers (CaCCinh-A01). <italic>In vivo</italic> airway reactivity, induced by histamine and methacholine, was expressed as specific airway resistance (sRaw) values. The number of citric acid-induced coughs was counted using a double-chambered body plethysmograph, and the frequency of ciliary beating (CBF) was assessed <italic>in vitro</italic> by brushing method. For comparison, salbutamol and codeine were tested under the same conditions.</p> </sec> <sec><title style='display:none'>Results</title> <p>The results showed significant differences in the responses of unsensitized and sensitized airways to both TMEM16 blockers administered. CaCCinh-A01 and benzbromarone significantly reduced the number of cough efforts in the group of OVA-sensitized guinea pigs. Significant improvement in sRaw values could be observed in OVA-sensitized TMEM16 blocker–treated animals compared to salbutamol when challenged with inhalational histamine, and the outcome was similar to salbutamol when challenged with methacholine. CBF was significantly inhibited in animals sensitized to OVA treated with selective inhibition of TMEM16A.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>The results demonstrated that treatment with blockers of TMEM16 can reduce both cough effort and sRaw, and the difference between TMEM16A-selective and TMEM16A-nonselective blocking is only negligibly in favor of CaCCinh-A01. It is also worthwhile to note the impairment of CBF in OVA-sensitized animals treated with CaCCinh-A01.</p> </sec> </abstract>ARTICLEtrue Multiple Unit Abuse-deterrent Dosage Form Based on Sodium Alginate<abstract> <title style='display:none'>Abstract</title> <p>There are several approaches for the formulation of abuse-deterrent, tamper-resistant, or alcohol-resistant dosage forms. This work is specifically focused on the formulation of microforms and multiple unit dosage forms with the mentioned resistant features. We prepared microcapsules based on sodium alginate by Ca<sup>2+</sup>-induced gelation, containing caffeine as a model drug. The prepared microcapsules were dried either by hot air or freeze-dried and the resistance in an alcoholic environment and the resistance against mechanical stress were observed. Subsequently, swelling studies were conducted to predict the behavior of prepared microcapsules during dissolution testing. Differences in the behavior of microcapsules during dissolution testing were strongly related to the different abilities of Ca<sup>2+</sup>-alginate microcapsules to swell in an acidic and alkaline environment. Alginate microcapsules exhibited gastro-resistant properties due to excellent swelling in an alkaline environment and poor swelling in a gastric environment. The addition of ethanol did not influence the swelling behavior of alginate microcapsules in the gastric fluid; rather, it showed the opposite effect, where swelling was slightly suppressed. Therefore, we conclude that alginate microcapsules are alcohol resistant. Also, they showed high mechanical strength, and therefore, grinding the microcapsules into a powder was impossible.</p> </abstract>ARTICLEtrue, antioxidant activity, and HPLC enantioseparation of aryloxyaminopropanols derived from naphthalen-2-ol<abstract> <title style='display:none'>Abstract</title> <p>The present work describes the synthesis, physico-chemical characteristics, antioxidative properties, and high-performance liquid chromatography (HPLC) enantioseparation of novel, potentially bioactive aryloxyaminopropanols – derivatives of naphthalen-2-ol modified in the basic part of their molecules. Reaction of naphthalene-2-ol with chloromethyloxirane leads to 2-[(naphthalen-2-yloxy)methyl]oxirane, which reacts in the next step with branched aliphatic amines (isopropylamine, <italic>tert</italic>-butylamine, and dimethylamine), aromatic amines (aniline, 3,4-dimethoxyphenylethylamine), and heterocyclic amines (pyrrolidine, imidazole, 2-methylimidazole, piperidine, morpholine, 4-methylpiperidine, or 2-methoxyphenylpiperidine). The target compounds were isolated in the form of free bases, as well as their salts with fumaric or hydrochloric acid. Their purity was established by thin-layer chromatography and their IR, UV, <sup>1</sup>H-NMR, and <sup>13</sup>C-NMR spectra were recorded. The antioxidant activities of prepared compounds were measured by the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method and they were compared with the values for the corresponding salts. Enantioseparation was accomplished by means of enantioselective HPLC using amylose tris(3,5-dimethylphenyl)carbamate (Chiralpak AD), as well as Chirobiotic T (native teicoplanin) in some cases.</p> </abstract>ARTICLEtrue Options for Mucoadhesive Dosage Forms for Use in the Oral Cavity<abstract> <title style='display:none'>Abstract</title> <p>Mucoadhesive dosage forms, which are used for topical application in the oral cavity, are currently a very intensively developing field in pharmaceutical technology. Considering the physiological conditions of the oral cavity, the formulation of these mucoadhesive forms is still a challenge. Various types and forms of polymers are used in the experiments, in combination with a large number of drugs, while the achieved effect can be local or systemic and the release rate can be controlled. For many drugs, buccal application is one of the ways to increase their bioavailability.</p> </abstract>ARTICLEtrue of Abstracts 39th Technology Days 7 and 8 September 2023 Processing of Dried Powdered Rosehips to Tablets Through Wet Granulation<abstract> <title style='display:none'>Abstract</title> <p>The pseudo-fruits of Dog Rose are a rich source of L-ascorbic acid and several other active substances, which means their high supportive therapeutic potential. The study aimed to examine the impact of the chosen technological procedure for the preparation of tablets containing rosehip powder on the amount of L-ascorbic acid in the final pharmaceutical form. Drying of the plant drug was performed at room temperature to avoid possible thermal degradation of this heat-sensitive compound. Similarly, drying of the granules after wet granulation in the oven was replaced by natural drying at room temperature. The composition of two types of prepared granule formulations differed in the filler – lactose (LAC) or microcrystalline cellulose (MCC). Apart from the disintegration test, they meet the technological requirements for granules or tablets. Lactose was confirmed as a more suitable filler, which despite the unsuccessful disintegration of the granules, ensures the disintegration of tablets within 15 minutes even without the addition of a special excipient acting as a disintegrant. The content of L-ascorbic acid detected using isotachophoresis – capillary zone electrophoresis was 87.16 ± 5.06 µg in LAC tablets and 63.33 ± 2.83 µg in MCC tablets.</p> </abstract>ARTICLEtrue as 3D Cell Models for Testing of Drugs<abstract> <title style='display:none'>Abstract</title> <p>Cell lines are an important tool for scientific research and clinical and pharmaceutical applications. Cells are isolated from animal tissues and can be expanded in culture to study cell biology and disease. The isolated cells can be used to produce antibodies, proteins, and vaccines. Immortalized cell lines can grow in vitro and are commonly used as models for complex biology. The most frequently used type of cell culture for scientific research and clinical and pharmaceutical applications is the two-dimensional (2D) model, but recently, the popularity of the three-dimensional (3D) cultivation method is growing.</p> </abstract>ARTICLEtrue of Properties of Dexamethasone Eye Drops<abstract> <title style='display:none'>Abstract</title> <p>During the development of medicinal forms (eye drops), it is necessary to consider several parameters, so that the medicine is nonirritating to the eye and, at the same time, has the desired effect. We prepared eye drops containing dexamethasone or its water-soluble salt in a 0.1% concentration. We compared suspension eye drops (with dexamethasone) and solution eye drops (with dexamethasone sodium phosphate) without viscosity adjustment as well as with viscosity adjustment by adding chitosan low molecular weight (LMW) with the mass-produced product Unidexa 1%. Acidity (pH), surface tension, density, viscosity, and irritability were evaluated. An <italic>in vitro</italic> or <italic>ex vivo</italic> test on human erythrocytes (red blood cells [RBCs]) was used to test irritability. Hemolysis of RBC was monitored by determining hemoglobin spectrophotometrically at a wavelength of 550 nm. The addition of chitosan 0.1% as a viscosity-increasing agent reduced the irritation potential of the experimental eye drops.</p> </abstract>ARTICLEtrue Laurate Tablets: Effect of the Excipients and Granule Size on the Tablet Quality<abstract> <title style='display:none'>Abstract</title> <p>Glyceryl laurate (GL) is a natural or synthetic surfactant with antiviral and antimicrobial activity and is not only effective in common colds or flu, but also against swine flu, herpes simplex, shingles, or chronic fatigue. The study aimed to formulate the GL granules as a semi-product for the compression of tablets and evaluate the influence of the substitution of sucrose laurate (Ryoto<sup>®</sup>) with sucrose ester (Sisterna<sup>®</sup>) in the composition of the granules and the effect of granule size on the quality of the compressed tablets. Four types of granules, varying in grain size and the type of additional surfactant, were prepared by melt granulation. The traditional pharmacopoeia tests were used to assess tablets’ quality. The granule size significantly affected all evaluated parameters: hardness, uniformity of mass, friability, and disintegration. The replacement of sucrose laurate with sucrose ester caused a slight decrease in tablet strength and a shortening of disintegration. However, it did not significantly impact friability and uniformity of mass. For this reason, the excipient, sucrose ester, can be evaluated as an adequate replacement in the composition of GL tablets.</p> </abstract>ARTICLEtrue