rss_2.0European Pharmaceutical Journal FeedSciendo RSS Feed for European Pharmaceutical Journal Pharmaceutical Journal Feed 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 Formulation Study of Ph-sensitive Gels<abstract> <title style='display:none'>Abstract</title> <p>Drugs remain for a short time on mucus membranes, such as oral, ocular, or nasal mucus, which are washed with physiological fluids. One of the possibilities to overcome this obstacle is the application of solutions that, due to the physiological environment or stimulus, turn into more viscous gels. These gels often also have mucoadhesive properties and the drug is released from them for a longer period. Carbomer 940 (C940), polycarbophil (PCP), and chitosan (CH) are gel-forming excipients, and the consistency of their solutions changes due to the concentration of protons (pH); therefore, they are referred to as pH-sensitive gelling agents. The aim of this study was to prepare pH-sensitive solutions that form gels in the pH of the oral cavity. We prepared water solutions with various concentrations of gel-forming excipients and evaluated the appearance, pH of the solution, injectability of the solution, and pH of gelation. By determining the pH of gelation, suitable concentrations (w/w) of the used polymers were found, namely, 0.1% C940, 0.225% PCP, and 2.5% CH with medium molecular weight (CHM). The 0.1% C940 and 0.225% PCP solutions were injectable through the syringe with the smallest 0.5 mm needle diameter. The 2.5% CHM solution was not injectable even through the syringe with the largest 0.8 mm needle diameter. Solgels prepared at the determined concentrations were evaluated by a dissolution test in a pH 6.8 phosphate buffer using methylene blue (MB) as a model substance. After 60 min of dissolution, 77.04% ± 5.94%, 48.85% ± 5.74%, and 77.35% ± 4.98% of MB were released from samples with C940, PCP, and CHM, respectively. The dissolution of the C940 and CHM samples took place according to the Korsmeyer–Peppas kinetic model (R2 0.999 ± 0.001, 0.978 ± 0.003) and of the PCP samples took place according to the first-order model (R2 0.994 ± 0.001). The 0.225% PCP pH-sensitive gel showed the most advantageous properties in terms of injectability, pH gelation, and prolonged release of MB.</p> </abstract>ARTICLEtrue of the Microscopic Method of Observing of the Oleogel Structure<abstract> <title style='display:none'>Abstract</title> <p>The subject of the research was the oleogel structure of the OraMAF oral suspension, containing a mixture of active substances in which the oleogel environment is formed by purified olive oil in combination with soy lecithin (SL) and sorbitan tristearate (STS). The objective of the research was the development of an optimal methodology for the work process, enabling microscopic observation of the structure of the oleogel suspension. Purified olive oil structured with a combination of gelators SL and STS with the addition of a solid phase of fucoidan (F) and chondroitin sulfate (CS) powders was used for the study as an alternative to OraMAF suspension. The sedimentation method of separation of the medium and staining of solid phases of the suspension brought the expected results, allowing the observation of the network structure of the gel, which consisted of interlaced gelator fibers assembling into star formations. The most interesting structures were clearly the star-like structures created from the star-shaped microtubules trapping the CS and F solid particles, colored blue.</p> </abstract>ARTICLEtrue as the Potential Delivery System for Nimodipine<abstract> <title style='display:none'>Abstract</title> <p>An important area of interest in pharmaceutical technology is the issue of poorly soluble drugs and their formulation into drug dosage forms that ensure optimal bioavailability. One of the options to solve solubility is the development of nanodispersion systems. This work is focused on the preparation of microemulsion systems suitable for poorly soluble drugs, for example, nimodipine. The composition and structure of microemulsion enable solubilization of different drugs and make it a universal drug carrier.</p> <p>Microemulsions increased the solubility of the model drug 20-fold compared to solubility in water. The use of mucoadhesive polymers – hydroxyethyl cellulose and xanthan gum – improved the <italic>in vitro</italic> release significantly. The highest amount of nimodipine was released from the microemulsion gel system with hydroxyethyl cellulose (1% w/w) and this depended on the diffusion of dissolved molecules.</p> </abstract>ARTICLEtrue Note of flow cytometric detection of intracellular SLAMF receptor-associated adaptor proteins SAP and EAT-2<abstract> <title style='display:none'>Abstract</title> <p>SAP and EAT-2 are intracellular adaptor proteins that link SLAMF receptors to downstream intracellular signalling pathways. Their expression and functions vary among different types of hematopoietic cells. The roles of SAP and EAT-2 in haematological malignancies are poorly understood. Here, we attempted to optimise a method for the detection of intracellular SAP and EAT-2 by flow cytometry. We found that using PerFix EXPOSE kit for cell fixation and permeabilization ensures optimal results in terms of staining intensity and signal-to-noise ratio.</p> </abstract>ARTICLEtrue changes in women with a medically indicated abortion: the study design<abstract> <title style='display:none'>Abstract</title> <p>A strongly psychosocially demanding situation in the life of a woman is the option of medically indicated abortion. Here we present the design of an ongoing study aiming to examine the stressfulness of life events related to medically indicated abortions by measuring cortisol concentrations in the participants’ hair and saliva. Pilot results show high salivary cortisol concentrations in the majority of the women one day before induced abortion. In half of the group, two months after the abortion, hair cortisol concentrations were higher in comparison to cumulative values from two months before. There were no changes in the second half.</p> </abstract>ARTICLEtrue Adverse Effects of Checkpoint Inhibitors: A Clinical Experience<abstract> <title style='display:none'>Abstract</title> <p>Autoimmune adverse effects of immune checkpoint inhibitors (ICIs) are rare but may be life-threatening. We performed a retrospective analysis of the immune-related adverse effects (irAEs) of ICIs in the Masaryk Memorial Cancer Institute (MMCI) from 2011 to 2021. The ICIs were administered to 648 patients. Severe irAEs were pronounced in 83 patients (12.8 %). Further, we report a case of severe irAE after treatment with ipilimumab and nivolumab. Prednisone, mesalazine, octreotide, infliximab, vedolizumab, and mycophenolate mofetil were used to manage G4 colitis, with partial response. Early diagnosis and appropriate management of irAE are essential in the perspective of further oncological treatment.</p> </abstract>ARTICLEtrue prevention of patients with ischaemic stroke after recanalization treatment<abstract> <title style='display:none'>Abstract</title> <p>We performed a retrospective analysis of 100 patients with ischaemic stroke. All patients underwent intravenous thrombolysis in the acute care setting (avg. 2.8 hours, max 4.5 hours) and 10 of them also underwent mechanical thrombectomy. For 20% of the patients, the stroke was fatal. Door to needle time was 38.46 minutes. Although changes in antithrombotic treatment were introduced due to strokes, there was no significant difference in National Institute of Health Stroke Scale scores between the patients who were on antithrombotic treatment and those who were on no antithrombotic treatment.</p> </abstract>ARTICLEtrue Extract of Red Cabbage Attenuates Advanced Alcohol Hepatotoxicity in Rats in Association with Mitochondrial Activity Modulation<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Aim</title> <p>The liver is the main target for alcohol-induced injury. The aims of this work were to carry out further research into the mechanisms of liver damage induced by long-term administration of high-dose ethanol to rats and to evaluate the hepatoprotective potential of red cabbage (<italic>Brassica oleracea</italic> var. <italic>capitata</italic> f. <italic>rubra</italic>) anthocyanins (RCE).</p> </sec> <sec><title style='display:none'>Material/Methods</title> <p>Male albino Wistar rats were divided into four groups. Group 1 was the control. Groups 2 through 4 received ethanol (4 g/kg body weight, 8 weeks). Group 3 received 11 mg RCE/kg and Group 4 received 22 mg RCE/kg. Dry lyophilised RCE was prepared from fresh red cabbage and analysed. We then evaluated the liver histology, mitochondrial respiration, and biochemical and immunological parameters in these groups of rats.</p> </sec> <sec><title style='display:none'>Results</title> <p>The rat intoxication caused steatohepatitis characterised by macro- and microvesicular steatosis, ballooning and fatty liver dystrophies, lymphocytic infiltration, neutral lipid accumulation, and elevations of the serum activities of the liver injury marker enzymes. The treatment of alcohol-administered rats with RCE (mainly, cyanidin-3-diglucoside-5-glucoside, cyanidin-3-coumaroylrutinoside-5-hexoside, cyanidin-3-feruloylrutinoside-5-hexoside, delphinidin-3-feruloylrutinoside-hexoside) dose-dependently alleviated these pathological changes: The sizes of hepatocyte lipid vacuoles and the inflammatory signs were decreased, and the levels of the rat serum biochemical markers of liver injury, proinflammatory cytokines TNFα and IL-6, and the adipokine leptin (and not TGFβ) were significantly reversed. The RCE administration during intoxication completely recovered the changed liver mitochondria respiration rates and the ADP/O coefficient, as well as the phagocytic index and neutrophil metabolic activity in the blood. In experiments in vitro, RCE (13.6 μg/ml) modulated the respiratory parameters of isolated rat liver mitochondria, dissipated mitochondrial membrane potential, and inhibited the Ca<sup>2+</sup>-induced mitochondrial permeability transition.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>The red cabbage anthocyanins could be useful for treatment of alcoholic liver injury due to their Ca<sup>2+</sup>-ionophoric/protonophoric activity, influence on Ca<sup>2+</sup> homeostasis, and improving mitochondrial functions and inflammatory status.</p> </sec> </abstract>ARTICLEtrue Use of Enzyme Systems of the Genus for the Production of Benzaldehyde<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Aim</title> <p>Benzaldehyde occurs in a number of plants, especially in the family <italic>Rosaceae</italic> and in particular in the genus <italic>Prunus</italic>. In nature, there are more than 100 genera and 3,000 species in the <italic>Rosaceae</italic> family. The objective of this study was to investigate the chemical composition of leaf essential oil of peach (<italic>Prunus persica</italic> L.) and cherry laurel (<italic>Prunus laurocerasus</italic> L.) as a new potential source of natural benzaldehyde.</p> </sec> <sec><title style='display:none'>Methods</title> <p>The essential oil was prepared by hydrodistillation, and chemical constituents were determined by GC-FID, GC-MS and chromatographic profiles were compared with each other.</p> </sec> <sec><title style='display:none'>Results</title> <p>The results show that essential oil obtained from peach and cherry laurel leaves appear to be a promising source of natural benzaldehyde. Under laboratory conditions the benzaldehyde content in peach and cherry laurel leaves reached 95.5% and 99.7%, respectively.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Laboratory and pilot experiments confirmed that by processing of 200–300 kg of green leaves of various species of the genus <italic>Prunus</italic>, especially peach and cherry laurel, 1 kg of benzaldehyde can be obtained.</p> </sec> </abstract>ARTICLEtrue