Article Category: Editorial
Published Online: Sep 21, 2021
Page range: 98 - 124
Received: Jun 22, 2021
Accepted: Jul 12, 2021
DOI: https://doi.org/10.2478/afpuc-2021-0010
© 2021 Molitorisová M. et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
The field of pharmaceutical technologies, medical devices and health technologies has not escaped the dynamics of technological innovations that are typical of the 21st century. The Department of Galenic Pharmacy (Pharmaceutical Technology) of the Faculty of Pharmacy of the Comenius University in Bratislava, in cooperation with the Slovak Pharmaceutical Society of the Slovak Medical Society will host the 38th Technological Days - an international forum for knowledge exchange between experts from several scientific disciplines interested in conventional and modern dosage forms.
This year's Technological Days thus builds on a long history, which began in 1967 in Smolenice, in what was then Czechoslovakia. Since 1991, the Technology Days has been organised on a biennial basis and alternated with the Pharmaceutical Technology Conference, which has been organised by the Faculty of Pharmacy of the Charles University in Hradec Králové. The 38th Technology Days under the auspices of the Dean of the Pharmaceutical Faculty of the Comenius University in Bratislava, Professor Ján Klimas, hosted a number of important guests from the Czech Republic and the UK. Further, for the first time in its history, it will allow a wide range of participants (pharmacy students, practitioners, scientific leaders in pharmaceutical, medical, chemical technology, process engineering and other disciplines) to access innovative solutions to current topics via online participation in the event.
The symposium covers the following:
Nanotechnology for Pharmaceutical Applications. This section will open with a presentation by a prominent academic, Professor Štefan Luby, concerning the state-of-the-art of Nanoscience – from the manipulation of atoms to human needs. Professor Luby draws attention to the area of novel approaches of nanomedicines and nanotechnology and highlights new challenges and opportunities, which can be also represented by graphene, the most studied nanomaterial today. A further state-of-the-art presentation, in the area of advanced drug delivery systems, will be delivered by Professor Daniela Uhríková, discussing the benefits of synergies of physics and pharmacy in the design of drug carrier systems using the example of lyotropic mesophases. Other topics include the use of natural and synthetic nanoparticles for the production of nanomedicine drugs, and various types of nanoparticle systems, including those that might be utilised in managing microbial resistance, as discussed by the research team of Doctor Tomáš Wolaschka. New scientific approaches in the development and production processes aiming at the realisation of the Quality by Design phenomenon. The application of the Quality by Design research of Professor Petr Zámostný into the formulation and design of a robust manufacturing process for solid dosage forms provides an extraordinary opportunity to understand an array of significant challenges that the sector faces today. The research of Associate Professor Zdeňka Šklubalová deals with the powder flow challenges, which occurred rather often during routines. The point is to offer scientific solutions to overcome the powder flow control problems. Professor Šklubalová's presentation provides an up-to-date record concerning the key findings and evaluates the new methodologies that open the door to a better understanding of powder specifications in terms of mechanisms of flow behaviour. Also discussed are the different dosage forms, focusing on other formulation issues (namely solubility, bioavailability, dissolution, etc.) and on quality control aspects such as microbial resistance or pharmaceutical analysis for the quality control of selected medicinal products and nutritional supplements, as presented by the team of Professor Peter Mikuš. Pharmaceutical compounding with applications in several areas of medicine, e.g. in dentistry, as presented by Doctor Margaréta Šubová, and an overview of magistraliter medicinal products by Doctor Veronika Šimunková offer a number of practical insights into pharmaceutical practice. The team of researchers, Doctor Simona Rohaľová, Doctor Jan Gajdziok and Doctor Tomáš Wolaschka, present a practice-related literature review on New technologies, including digitisation in medical devices and combination products, are experiencing an unprecedented ramp up, such as in application diabetology. The presentation in this area will focus on this context, which primarily involves the continuous monitoring of blood glucose using sensors and a smart insulin pump. In medical practice, such technologies have been used on the frontline and have become a standard part of the treatment of diabetes mellitus, as having been underlined by Doctor Vladimír Mičieta. Significant progress in digitisation has been also recognised in inhalation therapy, as will be examined by Doctor Mark Milton-Edwards. The mHealth phenomenon, according to Doctor Tomáš Fazekaš’ presentation, is becoming more and more available in many therapeutic areas, including in the context of Covid therapy management. Policy issues related to regulatory, funding, educational or legislative discussions are the subject of the panel discussion that closes the scientific event, with the participation of key representation of regulatory authorities, the state institutes for drug control from both countries, with the Czech Republic being represented by Doctor Darek Foit and Slovakia by Ing. Ivan Bernát. A panel discussion will be enriched by opinions and reflections from pharmaceutical practice by Doctor Ondrej Sukeľ representing the Slovak Pharmaceutical Chamber.
The ambition of the 38th Technology Days is to bring together physical, chemical, pharmaceutical, engineering and analytical sciences and to facilitate discussion between pharmacists working in different environments, i.e. in pharmacies, hospitals, the industry or regulatory area and academia, in order to continuously add value in bringing together their respective expertise on matters of importance to public health.
Boltnarová B.1*, Kubačková J.1, Holas O.1, Pávek P.2
Macrophages as phagocytic cells play an important role in our body's defence. In response to diverse stimuli, macrophages can polarise into several phenotypes with a different activity that affects the development of various diseases including cancer or chronic inflammation. Corticosteroids are among the stimuli that induce changes in polarisation from the proinflammatory phenotype of macrophages to the anti-inflammatory one. Although corticosteroids are potent anti-inflammatory substances, they cause serious side effects during therapy. Therefore, we prepared macrophages-specific poly(lactic-co-glycolic acid) (PLGA) nanospheres with incorporated dexamethasone (DEX) that can be therapeutically used in various indications with reduced harmful effects. Several types of PLGA, varying either in the ratio of lactic and glycolic acid or in the structure, were used for nanosphere formulation. The preparation was performed by two methods: nanoprecipitation and emulsification solvent evaporation. We obtained nanoparticles with a size range of 150–290 nm, which corresponds to the preferred size range for macrophage uptake. Nanospheres with zeta potential ranging from −10 to −15 mV were sufficiently monodisperse with a polydispersity index under 0.2. The loading efficiency of DEX surpassed 25%. This indicates that DEX-loaded nanospheres are a promising tool for corticosteroid site-specific delivery. For biological evaluation, the human monocyte cell line THP-1 was used. THP-1 monocytes were differentiated into macrophages by phorbol 12-myristate 13-acetate (PMA). Cytotoxicity tests by MTS assay and immunogenicity tests by qRT-PCR were performed to determine the biological response of the cells to our DEX-loaded PLGA nanospheres.
Dudík B.1–3*, Zonnenschein T.1, Komjáthy H.4, Slimáková L.2
On 21 December 2020, the European Medicines Agency recommended registration of the first vaccine for the prophylaxis of COVID-19. On 26 December, the first person was vaccinated in Slovakia, and since that date, vaccination has been continuing throughout the country. Hospital pharmacists have been involved in the vaccination process from the beginning, as all medicines used in hospitals are received and stored in hospital pharmacies. Due to the nature of the first vaccines, the so-called mRNA vaccines that are sensitive to manipulation and require special handling, we took responsibility for diluting and pre-drawing individual doses in syringes. Following the example of our hospitals, many other hospital pharmacies throughout Slovakia also took part in the preparation of vaccines, which made pharmacists and pharmaceutical technicians part of vaccination centres. We ensured the most correct and safe (both for the patient and for the vaccine itself) preparation; also, we relieved the nurses and doctors, and thus helped smooth running of the vaccination, which is extremely important in the fight against a pandemic. In addition, we have gained new experiences and potentially new opportunities to help not only other healthcare professionals, but also patients in the future.
Fazekaš T.1*, Mináriková D.2, Mikulášová A.2
Detailed understanding of the technology acceptance key factors by the population may help to control the spread of the SARS-COV-2 virus. The pandemic stimulates scientists to develop methods of telemedicine by using mobile phones. Simplest applications, like Docandu, Mediktor or COVID. Termini.app, are just used to record symptoms. Tests based on the principle of anterior nose swabs can be performed by the patients themselves in Cuehealth, Ellumehealth and EverlyWell. The antigen test set contains an analyser connected via Bluetooth. Artificial intelligence in Coughvid and Vocalishealth recognises changes in the human voice (e.g., dry cough). COROWELL and USMELLIT allow testing anosmia. These applications evaluate the correctness of smell recognition. Popular blood tests like Racordiax and Exa-Health are using mobiles to evaluate results. Bloomdiagnostics detects the amount of antibody to the virus. The smartphone camera in Docdot records the light reflected by capillaries located below the surface of the skin, allowing real-time vital sign measurements. It is clear from this short overview that a diverse range of technologies as well as applications are available. Preliminary results of our ongoing research confirm that trust, threat perception, health motivation, perceived benefits, perceived barriers, hedonic motivation, price value, habit and demographic attributes are the most important factors. A new questionnaire, based on the Health Believes Model and the Unified Theory of Acceptance and Use of Technology extended by ‘COVID-specific terms’, was created in the Slovak language. The prototype was reviewed for content validity by a group of university staff. The questionnaire is currently in the pilot phase before administration in the proposed study. The final questionnaire will be distributed online on a selected mix of social network groups to a random sample of respondents. Reliability and construct validity analyses will be conducted on the final data. Because the pandemic has brought the need to integrate new technologies more effectively into our lives, our research shows that it is possible to rapidly achieve success through an approach with the right conceptual model. Our main research hypothesis states that trust is the key factor of our extended technology acceptance model, which plays the main role in the acceleration of mobile technology use, at least in the fields of telemedicine, telemonitoring and telediagnostics.
Fečkaninová A.1, Chomová N.2, Wolaschka T.1*, Mudroňová D.2, Franc A.3, Koščová J.2, Popelka P.4
Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Research in probiotics for aquaculture is at an early stage of development and much work is still needed. Therefore, the aim of the work was to prepare probiotic feed using modified coating technology, perform pharmacopoeial tests and subsequently observe the survival of probiotic bacterial cells in pellets during the storage period. The feed was coated in two layers. The first powdery coating layer consisted of colloidal silicon dioxide. The second layer was formed with probiotic bacterial cells of
Husár Š.*, Chomaničová K., Rumlová K., Sýkorová M.
Highly potent substances are a class of extremely active biological compounds and produce intensive effects at low doses. In this review, we discuss the challenges and opportunities to develop novel highly potent and low-dose pharmaceutical products and how they differ from the development of standard high-dose formulations. Pharmacokinetic parameters of highly potent products vary extensively within and between individuals due to assay variations and differences in the amount of hepatic metabolism of different ethnic groups. Therefore, the selection of the study population should also be considered in high-potency drug product development planning. Many active substances undergo extensive pre-metabolisation through CYP3A4 system, and different highly potent compounds themselves have varying effects on CYP enzymes. They may also affect the metabolism of other drugs, leading to issues with efficacy or safety. The present article is focused on the preparation and analytical evaluation of prolonged-release highly potent drug forms and the release kinetics characterisation from different matrix systems that exhibit alcohol and abuse resistance by various manipulation techniques. Sustained-release formulations provide uniform concentration within a therapeutic range, reduce the dosage frequency and minimise the side effects associated with the drug by avoiding dose dumping phenomenon.
Klacsová M.*, Čelková A., Búcsi A., Uhríková D.
The influenza virus is the main cause of viral airway infections occurring worldwide and is related to severe annual epidemics. Currently, few drugs are available to treat pulmonary viral infections, like oseltamivir (Tamiflu®) administered orally, zanamivir (Relenza®) administered by inhalation, intravenous peramivir (Rapivab®) and laninamivir (Inavir®) taken as a single inhaled dose of dry powder. These antivirotics bind to and inhibit the active site of the neuraminidase enzymes, which are essential for the release of progeny virions from the infected host cells, and thus reduce viral replication.
A huge effort is made to develop new orally administered neuraminidase inhibitors with sufficient bioavailability and optimal drug formulation. Liposomes are largely used as drug carriers for both lipophilic and hydrophilic drugs. Lipophilic drugs are embedded within the lipid bilayer, while hydrophilic drugs are enclosed in the water core of the liposome.
In this work, we studied the physicochemical properties of oseltamivir–liposome and zanamivir–liposome complexes and compared them to some reference inhibitors of cysteine proteases of coronaviruses encapsulated in model liposomes. The lipophilicity of studied drugs was defined by determination of their lipid–water partition coefficient. The size of drug–liposome complexes was investigated by dynamic light scattering. Due to the interaction of a drug with membrane lipids, their thermodynamic parameters, pre-transition and main phase transition temperatures, and transition enthalpies are influenced. These parameters were studied by differential scanning calorimetry. The excimer fluoresce was used to study the effect of antivirotics on the lateral pressure profile across the lipid bilayer. Obtained results allow us to deduce structural and thermal stability and potential drug release from liposomal formulations.
Macho O.*, Čierny M., Gabrišová Ľ.
Received 14 April, 2018, accepted 1 June, 2018
This work aimed to describe the influence of parameters of high shear granulation, impeller speed, liquid to solid ratio and wet massing time on the yield of the granulation process and the size and shape of created granules. The experimental material was Avicel® PH101 microcrystalline cellulose commonly used as a dry binder/filler in solid dosage forms. Aqueous solutions of polyvinylpyrrolidone and polyethylene glycol were used as granulating liquids. The experiments were performed in devices with volumes 1 and 6 l. The size distribution of the dried granules was determined using a PartAn 3D particle size and shape analyser by dynamic image analysis. Higher impeller speeds resulted in greater dynamic stresses on the particles in the granulator, which resulted in the formation of smaller granules. With increasing liquid to solid ratio, the size of the granules first increased linearly, and with further addition of the granulating liquid, the size began to increase sharply. The parameter liquid to solid ratio had a significant effect on the process yield. By monitoring the impeller torque, it was possible to classify the individual phases of the process, up to a plateau characterising the balance between the formation and breakage of granules.
Mikušová V.1*, Mikuš P.2
Received 14 April, 2018, accepted 1 June, 2018
Chitosan is an amino polysaccharide produced from chitin by partial deacetylation in an alkaline environment. It has cationic nature; it is non-toxic, odourless, biocompatible and biodegradable. Besides this, chitosan offers bacteriostatic, fungistatic, haemostatic, spermicidal, anticholesteremic and anticarcinogenic properties. It has vast possibilities of chemical modifications leading to novel properties useful in nanomedicine. Chitosan offers outstanding biological properties due to which it has gained enormous importance in various applications in pharmaceutical and biomedical areas, e.g., in drug delivery, vaccine delivery, gene delivery, tissue engineering, etc. For controlled drug delivery systems, it offers
Chitosan nanoparticles (NPs) act as an excellent drug carrier because of the above-mentioned intrinsic beneficial properties of chitosan itself, easy preparation, their small size and target specificity triggered, to some extent, by their positive surface charge. Other benefits of chitosan NPs in drug delivery include the potential of the reversible opening of tight junctions, enhanced dissolution of poorly soluble drugs, mucoadhesivity, improvement of drug stability and its efficacy and decrease of possible side effects of drugs. They are widely used as drug delivery systems also because of their ability to load a wide range of natural and chemical agents/drugs; peptides, proteins, oligosaccharides and nucleic acids are some of these.
The aim of this work is to discuss recent advances in using chitosan NPs as a significant tool in drug delivery systems and their application possibilities via various routes of administration such as oral, parenteral, pulmonary, ocular, nasal, vaginal, dermal and transdermal.
Sklenář Z.*
Received 14 April, 2018, accepted 1 June, 2018
Although drug compounding has a long tradition in the Czech Republic, too, the almost constant and somewhat limited supply of pure substances has been obstructing the development of new formulas for many years. From January 2010 till December 2020, more than 60 compounds have been available as substances with quality certificates, based on the requests of physicians and pharmacists. Based on the creation of new magistral formulas with application in human and veterinary medicine is possible. The paper aims to inform about the new possibilities of extemporaneous (magistral) preparation, including some examples of new formulas that were created and have been verified in practice. Examples of suitable magistral formulas are presented that can replace registered products which are not readily obtainable. Due to creation of new formulas, the use and importance of compounded preparations in the Czech Republic has increased.
Sýkorová M.*, Birošíková K.
Medicines are defined as articles intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease and as articles intended to affect the structure or any function of the body of humans or animals. A medical device means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, in human beings for one or more of the following specific medical purposes and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but may be assisted in its function by such means.
Šimunková V.*
The
Šklubalová Z.*
Flowability of particulate materials is influenced by many factors which include properties of the material itself, external conditions as well as the method used. In order to describe material behaviour, a combination of results obtained by different testing methods is necessary. Conventional methods of routine testing are targeted to check the quality of entrance powder materials, either active substances or excipients, to define the geometrical parameters of bins for transport and storage, or to optimise the flow properties of powder mixtures in the production of dosage forms, e.g., tablets or capsules. New methodologies in conventional testing, such as a dynamic of tapping, or new methods such as avalanching and powder rheology open the door to a detailed study of interparticle interactions in bulk powders in order to better describe the mechanisms of flow behaviour. From this point of view, powder flowability testing remains challenging.
Šnejdrová E.1*, Martiska J.2, Loskot J.3
One of the most common complications in orthopaedic surgery is musculoskeletal infections. The use of an antibiotic-loaded depot-based drug delivery system locally can decrease the toxic systemic effect. In this study, a broad-spectrum antibiotic, rifampicin, was incorporated into poly(lactic-co-glycolic acid) (PLGA) derivatives varying in molar weight, lactic to glycolic acid ratio and molecular architecture. The nanoparticles (NPs) were formulated by the nanoprecipitation method. The polymer and the drug were dissolved in DMSO and injected into an aqueous solution of a stabiliser. The raw nanosuspension was centrifuged and the NPs were stabilised by lyophilisation employing trehalose or mannitol as cryoprotectants. The size, polydispersity, zeta potential, encapsulation efficiency, loading capacity and dissolution profile of rifampicin were determined. Depending on the concentration of the polymer in the organic phase and its molar weight, NPs in the range of 140–330 nm with polydispersity lower than 0.2 were obtained. The SEM demonstrated spherical shape of the NPs, and the software-determined size of the NPs confirmed the results obtained by dynamic light scattering. A 0.5% poloxamer 407 solution was the most effective for steric stabilising of NPs under given formulation conditions, and the use of 0.01% didodecyl dimethylammonium bromide solution resulted in stable and positively charged NPs. The encapsulation efficiency ranged from 17% to 53% and the loading capacity reached 10%, showing that the polymer carrier significantly predominated in the NPs. The release profile proved a burst release, which can be attributed to the surface-associated drug, followed by a slower sustained release phase. Thanks to the large surface area, biodegradability, hydrophobicity and cationic charge, PLGA NPs with rifampicin could be used not only to treat musculoskeletal infections, but also as antibacterial local carriers to fill cavities and defects.
Šubová M.1,2*, Krchňák D.2,3
Dental medications intended for application to the oral cavity and oral pharynx are used in dental care, in inflammatory diseases of the oral cavity, as well as to prevent the development of dental caries. They most often occur in the form of gargles and rinses, as well as ointments, gels, pastes or oral beads. Despite the full range of mass-produced medicines for dentistry, compounding is very important because of occasional outages or the long-term unavailability of these products on the market. Drugs such as astringents, disinfectants, antiseptics, antibiotics, antiphlogistics, local anaesthetics and drugs with epithalising effects are most commonly formulated into magistral formulations. The most often prepared medications include solutions of iodine, chlorhexidine digluconate, menthol and dexpanthenol, as well as suspensions with nystatin, oral gels with miconazole, endodontic pastes with tetracycline hydrochloride and dexamethasone, mucoadhesive pastes with local anaesthetics, dexpanthenol and corticosteroids. As to the preparations intended only for direct and expert use by a dentist, mention may be made of an etching gel with phosphoric acid, which is intended for etching crowns, or a solution of xylometazoline for anemisation. ‘Pulpodent’ – a paste containing paraformaldehyde, lidocaine, thymol, clove oil and Peru balsam – can be attributed a special position within this category of products. Pulpodent is a suitable substitute for a mass-produced drug that is no longer available on the market. Dentists use it to achieve pulpal anaesthesia. Semi-solid drugs represent the majority of drugs prepared for dentistry. In the case of ointments – zinc paste, white soft paraffin, or macrogol ointment are used as bases. In the case of gels, gelling agents as methylcellulose, hypromellose or colloidal anhydrous silica are used. Mucoadhesive pastes are a special application form. They are generally prepared by dispersing the drug with a gelling agent in a lipophilic base (e.g., soft paraffin). After contact with the mucous membrane of the oral cavity, an
Tranová T.*, Mužíková J.
Orodispersible tablets (ODTs) are described as solid dosage forms that disintegrate in the oral cavity within a few seconds in the saliva before swallowing. ODTs can be used for indications where the rapid onset of action of the drug is important, such as migraine, vomiting or a hypertensive crisis.
The ODTs must have a rapid disintegration time (up to 30 s as required by the USP and FDA) and sufficient tensile strength. They should also cause a pleasant mouthfeel and mask the bitter taste of the drug. There are many methods for preparing ODTs. Conventional technologies include direct compression, lyophilisation, molding, cotton candy process, spray drying, extrusion, melt granulation and sublimation.
The simple, most economically advantageous and productive method of ODT preparation is direct compression. ODT formulations produced by direct compression must contain a dry binder, usually mannitol, and a superdisintegrant. An innovative approach to simplify and speed up the direct compression process is the use of co-processed dry binders. They comprise two and more excipients with different functions, which ensures their multifunctionality. For ODT formulations, that often contain a large number of excipients, are these co-processed dry binders very beneficial and their composition is essential for functionality in the ODT. In addition, they can speed up both the production process and the entry of new products into the market without the need for extensive and expensive testing. Examples of co-processed dry binders for the preparation of ODTs are Prosolv® ODT G2, Ludiflash®, Parteck® ODT, Disintequik®, Pharmaburst® and Pearlitol® Flash.
Vařilová T.*, Svačinová P., Šklubalová Z.
In order to increase the dissolution rate of poorly water-soluble drugs listed in the second class of Biopharmaceutical Classification System (BCS II), a spray drying method can be employed. In this work, the effect of spray drying on the dissolution rate of meloxicam (MX), a model analgetic drug, was investigated. Forty or 50 mg of MX was dissolved in 200 ml of purified water in the presence of surfactant sodium lauryl sulfate (SLS, 3%). Finally, a chitosan carrier (5 %) was suspended in the mixture. Prepared dispersions were spray dried at 170°C, 190°C and 210°C using a nozzle with a diameter of 1.4 mm (BÜCHI Mini spray dryer B-290). The irregular particles of the carrier with adhered MX particles were detected by optical microscope (Olympus BX 51) and scanning electron microscope (Phenom Pro). The thermal properties of products were evaluated by differential scanning calorimetry (Netzsch DSC 200 F3 Maia). Thermograms displayed crystalline form of MX; good stability after 6 months of storage at room temperature was found. From the obtained dry powder, 500 mg tablets were prepared (T1-FRO 50 Zwick/Roell, 4 kN) to study the drug dissolution rate (USP 1 – Sotax AT7 Smart, 500 ml of phosphate buffer of pH 6.8, 37°C ± 0.5°C). The results showed an increase in the drug dissolution rate by 40%–60% within 2 h compared to pure MX. Spray drying of chitosan suspension in the aqueous solution of MX solubilised by the addition of SLS showed a pronounced effect on the dissolution rate of the drug. The main reason is the preparation of interactive mixtures in which particles of MX spread onto the surface of chitosan particles are better available for the dissolution medium. The polymorph type of MX has to be studied further.
Wolaschka T.*, Rohaľová S., Kľoc D., Fečkaninová A.
A number of antibiotics (ATB) are used in clinical practice. Their improper or inappropriate use has developed bacterial strains resistant to previously effective ATB. There are several mechanisms of microbial resistance to ATB: (a) decreased ATB influx: specific transport proteins that reduce the effective concentration of ATB cause increased ATB efflux; (b) genetic modification of the ATB site action (penicillin-binding protein, DNA gyrase, topoisomerase IV); (c) enzymatic inactivation of ATB by β-lactamases, transferases that convert ATB to an inactive metabolite; (d) increased production of the competitive substrate of the ATB-binding site can lead to bacterial resistance to sulphonamides; (e) the biofilm environment in which bacteria more easily resist the action of various ATB contributes to resistance; (f) development of metabolically inactive persistent bacteria that do not respond to ATB and (g) swarming of bacteria into a raft-like structure in which many are multi-resistant. Intracellular microorganisms are naturally protected against the influence of ATB, which must cross the plasma membrane of the host cell.
The aim of this study was to point out the actual possibilities of pharmaceutical technology in managing microbial resistance, where nanoparticles (NPs) appear to be a promising solution. The positively charged surface of the dendrimers binds to the negatively charged microbial membrane, thereby increasing its permeability. Liposomes release large amounts of incorporated ATB in bacterial cells by endocytosis. Decreased ATB efflux by P-glycoprotein was observed in polymeric and solid lipid NPs. NPs allow the synergistic application of ATB combination in a single NP, thereby increasing the effective concentration at the site of action. NP of silica with nitric oxide and NP of silver inhibit biofilm formation and eliminate the microorganisms present in it. Phagocytosis of NP by host macrophages provides high concentrations of ATB, thereby effectively eliminating intracellular bacteria. The development of resistance to NP with several mechanisms of antibacterial action (containing nitric oxide, chitosan and various metals) is unlikely. Active targeting with bound ligand or antibody contributes to the specific action of NP. In connection with the elimination of cytotoxic, genotoxic, immunotoxic effects of NP, some authors point to organic NP, which is prepared using plant extracts or microbial cultures.
Zámostný P.*, Bittner R., Komínová P., Marinko N., Petr J., Römerová S.
Development of a solid dosage formulation and process for manufacturing thereof can present a significant challenge even nowadays. This fact results from firstly, the need for a robust process, which can accommodate the variability in drug material procured from several different global producers. Secondly, it results from the increased competition on the generic drug market, which makes the production costs critical at a previously unprecedented level, bringing incentives for using cost-efficient technologies, such as direct compression or roll compaction in a much broader range of applications. The Quality by Design (QbD) approach is often used to deal with the challenges, but it requires more knowledge about the process and the raw materials used therein. Thus, the formulation and the process development are much more in line with the scientific understanding than ever before. In the field of compacted solid products, rigorous compaction analysis presents an essential tool for developing a well-balanced formulation and designing a robust manufacturing process. It involves the well-established measurement of viscoelastic properties of particulate formulation to maximise the formulation ‘plasticity’ required for strong tablets. However, it can also include measuring particulate material propensity to friction or sticking to predict tablet ejection phenomena, or slug transfer into capsules, performing texture analysis to determine tablet propensity to local failures, such as chipping, or compacted ribbon ability to form a good dry granulate, and analysis of compressed products’ porosity and phase composition micro-structure development under applied stress to predict and tailor the disintegration and dissolution performance of the final product. In line with the indicated scope, the presentation will provide an overview of the fundamental principles, the techniques for measuring key parameters and the application thereof to design better solid dosage forms using several case studies from the industry and opening a further prospect for industrially related research in this field.
Čelková A.*, Búcsi A.
Liposomes are widely used drug delivery systems. Recently, lipid vesicles have been used in the formulation of two types of vaccines for the prevention of COVID-19. The aim of the work was preparation of unilamellar liposomes with reproducible properties using a new extruder LiposoFast-LF50. This device can produce 5–50 ml of unilamellar liposomes in comparison to a mini-extruder with a maximal volume of 1 ml and an effective yield of about 800 μl. At first, we prepared multilamellar liposomes composed of 1,2-dipalmitoyl-
Čierna M.1*, Mučaji P.2, Špaglová M.1, Čuchorová M.1, Krchňák D.1
The study aimed to isolate psyllium mucilage from psyllium husk, which is gained from the plant
Čuchorová M.1*, Špaglová M.1, Čierna M.1, Mesárošová D.2
This work was aimed at the preparation and subsequent characterisation of the thermosensitive poloxamer gels – triblock copolymers of polyoxypropylene and two hydrophilic chains of polyoxyethylene. They can modify their internal structure due to temperature because of changes in the intermolecular interactions (ionic, hydrogen bonding, hydrophobic forces) and swell
Mikušová V.1*, Ferková J.1, Špaglová M.1, Krchňák D.1, Mikuš P.2
The hydrogels containing semi-synthetic cellulose derivatives as gelling agents are widely used due to their safety, biocompatibility, biodegradability and a relatively easy way of preparation and low price. The aim of this work was to comprehensively study the rheological and texture properties of five different semisynthetic cellulose hydrogels, namely methylcellulose (MC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), carboxymethyl cellulose (CMC) and sodium salt of carboxymethyl cellulose (NaCMC), for the liberation of model drug ibuprofen. In the first step, rheological properties of the hydrogels as dependencies of shear stress on the shear rate were evaluated to recognise the type of flow (Newtonian, pseudoplastic or plastic). Based on viscosity values, three categories of hydrogels were selected, i.e., low, medium and high viscous, and two other categories (including 4% and 6% HEC, 4% and 6% MC, 2% HPMC, 6% CMC and 8% and 10% NaCMC) were further studied for texture properties. In the second step, hardness, adhesiveness, minimal retracting force and maximal compression were evaluated by texture profile analysis. The adhesiveness ranged in the interval of 5.99–32.688 g s. In the final step, the liberation of ibuprofen from these hydrogels was evaluated. The amount of released ibuprofen in 150 min increased in the order 10% CMC (51.2%), 4% MC (52.5%), 6% HEC (53.3%), 6% MC (54.3%), 8% CMC (56.8%), 2% HPMC (56.9%), 4% HEC (57.0%) and 6% NaCMC (59.7%). Also, 6% hydrogel of NaCMC was chosen as the optimal for its dermal application with respect to the best liberation of ibuprofen and acceptable adhesiveness, hardness and viscosity. In continuation of this study, various permeation enhancers will be evaluated for further enhancement of ibuprofen liberation.
Rohaľová S.1,2, Wolaschka T.2*, Gajdziok J.1
Dental caries, periodontal diseases, stomatitis, tooth loss and cancer are the most common diseases affecting the oral tissues. The efficacy of the pharmacotherapy of these conditions is significantly affected by the dosage form. In the last two decades,
This work provides an insight into the treatment of oral diseases using
Exactly 592 works, 224 patents and 10 clinical trials on
Asi Shirazi A.1*, Keshavarzi A.1, Královič N.1, Klacsová M.1, Bastos M.2, Uhríková D.1
Pulmonary surfactant (PS) is complex of lipids (90 wt%) and a few specific proteins (10 wt%), which are produced by type II alveolar cells. DPPC (Dipalmitoylphosphatidylcholine) is the most abundant lipid in pulmonary surfactant, representing almost ~40% of the total surfactant mass. PS is responsible for lowering the surface tension in the liquid-air interface, therefore preventing alveolar collapse during expiration.
Currently, exogenous PS are being used mostly in therapy of neonates’ respiratory distress syndrome RDS. Since they are derived from animals, their production are financially demanding, hence synthetic production of pulmonary surfactants shows its importance.
Cathelicidin belong to antimicrobial peptides group (AMP). It is cationic, amphipathic peptide that kills bacteria by invading the membrane structure potently. Therefore, the effect of such peptides on membranes and the relevance of membrane lipid composition have been topics of interest back in decades.
We studied the interaction of cathelicidin peptide LL-37 with model system of PS composed of DPPC/POPC/PLPC/POPG = 50:24:16:10 wt%. Unilamellar vesicles were prepared by extrusion. The effect of LL-37 on the size and surface charge of model PS liposomes was examined using dynamic light scattering technique (DLS) and zeta-potential measurements. The effect of LL-37 on temperature of main phase transition from solid gel phase to liquid crystalline phase was derived using differential scanning calorimetry (DSC).
Acknowledgement: This research was supported by APVV-17-0250, APVV SK-PT-18-0032 and VEGA 1/0223/20 grants and JINR project 04-4-1142-2021/2025.
Keshavarzi A.1*, Asi Shirazi A.1, Klacsová M.1, Búcsi A.1, Bastos M.2, UhríkováD.1
Pulmonary surfactant is a lipoprotein complex produced by type II alveolar epithelial cells in lungs. This complex is essential for reducing surface tension of the air-liquid interface and therefore facilitating gas exchange. Animal derived exogenous surfactants are used clinically in neonatal medicine. Due to their physiochemical properties, exogenous pulmonary surfactants can be used as delivery vectors for other drug molecules. However, the effect of addition of other drug molecules on the physico-chemical properties of pulmonary surfactant must be examined.
Budesonide which has better lipophilicity in comparison to other glucocorticoids, could be used in treatment of meconium induced lung injuries. We studied the effect of budesonide on physio-chemical properties of lipid bilayer mimicking the composition of pulmonary surfactant. The model system of lung surfactant was prepared as a mixture of lipids occurring in native human surfactant (DPPC and POPG 1:1wt). Due to the drug incorporation, the size and the surface charge of the unilamellar liposomes prepared from the mixture was investigated by dynamic light scattering and zeta potential measurements, respectively. Differential scanning calorimetry was used to determine the effect of drug on the temperature of phase transition from gel to liquid crystalline state.
Acknowledgement: This research was supported by APVV-17-0250, APVV SK-PT-18-0032 and VEGA 1/0223/20 grants and JINR project 04-4-1142-2021/2025.