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The global impact of drug shortages on healthcare systems is a concerning issue that needs urgent attention. These shortages not only jeopardize patient care, public health, and healthcare delivery but also pose distinct challenges for pediatric populations due to their specific medication requirements and vulnerabilities. It is imperative to address this issue to safeguard the health and wellbeing of this specific age group. This review Gaimed to conduct a systematic analysis of strategies for addressing drug shortages in pediatric care from 2014 to 2024. The search included five databases: PubMed, Reaxys, Embase, Scopus, and Science Direct, using the keywords “drug shortage” and “pediatric”. The final protocol was developed following the guidelines outlined in the " The PRISMA 2020 statement: An updated guideline for reporting systematic reviews”. In total, 234 publications were identified. After screening the search results and applying inclusion and exclusion measures, a total of 27 original research papers were included. The primary finding indicates that a comprehensive approach rooted in risk management can significantly mitigate drug shortages in pediatric settings. This approach should address underlying causes such as manufacturer and delivery challenges and focus on prevention through enhanced forecasting and vigilant shortage monitoring. The most prevalent response involved seeking alternative treatment options. It is imperative to implement institutional and national guidelines, foster communication, and provider education, and minimize waste to effectively mitigate drug shortages in pediatric settings.

A novel ophthalmic delivery system utilizing levofloxacin-loaded, preservative-free, nanofiber-based inserts was investigated. Polyvinyl alcohol (PVA) and Poloxamer 407 (Polox)were employed as matrix materials, while hydroxypropyl-beta-cyclodextrin (HP-β-CD) was a solubilizer. The formulations were prepared via electrospinning and characterized for fiber morphology, drug dissolution, cytotoxicity, and antimicrobial activity. Scanning electron microscopy confirmed uniform fibrous structures. Fourier Transform Infrared spectroscopy and X-ray diffraction analyses demonstrated the amorphous state of levofloxacin within the fibers. In vitro dissolution studies revealed a rapid (within 2 min) and complete drug release, with higher HP-β-CD levels slightly delaying the release. Cytotoxicity tests showed increased HP-β-CD concentrations induced irritation, that was mitigated by sodium hyaluronate. The antimicrobial efficacy of the nanofibers was comparable to conventional eye drops, with lower minimum inhibitory concentrations for most tested strains. The nanofibrous formulation prepared from a PVA–Polox-based viscous solution of the drug:CD 1:1 mol ratio, containing 0.4% (w/w) sodium hyaluronate) was identified as a particularly promising alternative formulation due to its rapid and complete dissolution, good biocompatibility, and effective antimicrobial properties. Its gelling properties indicate that the residence time on the eye surface can be increased, potentially reducing discomfort and enhancing therapeutic outcomes. The nanofibrous formulations enhanced antimicrobial efficacy, providing a preservative-free alternative that minimizes the potential eye irritation that might occur because of the preservative agent and reduces the administrated dose frequency by extending the drug’s retention time on the eye’s surface. Subsequently, it improves patients’ adherence, which would reflect positively on the bioavailability. The levofloxacin-HP-β-CD nanofibers demonstrate promise as an alternative to traditional eye drops, offering advantages in solubility, stability, and patient compliance for ocular infection treatment.

Nanofibers can be utilized to overcome the challenges faced by conventional ophthalmic formulations. This study aimed to develop and characterize cysteamine (Cys)-loaded nanofiber-based ophthalmic inserts (OIs) as a potential candidate for the treatment of ophthalmic cystinosis using water-soluble polyvinyl alcohol (PVA)/poloxamer 407 (PO-407) and water-insoluble tetraethoxysilane (TEOS)/PVA nanofibers. Plain and Cys-loaded fibers in different proportions were prepared by the electrospinning method and studied for their morphological, physicochemical, release study, cytocompatibility effects, and stability study. The fiber formation was confirmed by scanning electron microscopy, while Fourier transform infrared spectra showed the most critical peaks for the Cys and the excipients. The release of the Cys was fast from the two polymeric matrices (≤20 min). The release from TEOS/PVA nanofibers is characterized by Case II transport (0.75 < β < 1), while the release from PVA/PO-407 nanofibers follows Fickian diffusion (β < 0.75). The cytocompatibility of compositions was confirmed by hen eggs tested on the chorioallantoic membrane (HET-CAM) of chick embryos. All formulations remained stable under stress conditions (40 ± 2 °C, 75 ± 5% relative humidity) regarding morphology and physicochemical characteristics. The developed nanofibrous mats could be an excellent alternative to available Cys drops, with better stability and convenience of self-administration as OIs.

This systematic review offers a comprehensive analysis of plant-derived extracellular vesicles (PDEVs) as emerging drug delivery systems, focusing on original research articles published between 2016 and 2024 that exclusively examine the use of PDEVs for drug delivery. After a rigorous search across multiple databases, 20 relevant studies out of 805 initial results were selected for analysis. This review systematically summarizes the critical data on PDEV components, isolation methods, and drug-loading techniques. It highlights the potential of PDEVs to significantly enhance drug safety and efficacy, reduce dosage and toxicity, and align drug development with sustainable and environmentally friendly biotechnological processes. This review also emphasizes the advantages of PDEVs over mammalian-derived vesicles, such as cost-effectiveness, higher yield, and reduced immunogenicity. Additionally, it explores the synergistic potential between encapsulated drugs and bioactive compounds naturally present in PDEVs. This study acknowledges the challenges in standardizing isolation and formulation methods for clinical use. Overall, this review provides valuable insights into the current state and future directions of PDEV-based drug delivery systems, highlighting their promising role in advancing pharmaceutical research and development.

Melatonin’s cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin’s clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013–2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.

Abstract Extracellular vesicles (EVs) are cell-derived, membrane-enclosed particles with the potential for a wide range of future therapeutic applications. However, EVs have almost always been administered by direct injection, likely hindering their efficacy because of rapid clearance from the injection site. The present study aimed to incorporate medium-sized extracellular vesicles (mEVs) into fast-dissolving electrospun polyvinylpyrrolidone-based nanofibers to explore the storage-dependent structure–activity relationship of the resulting nanofibrous formulations. Aqueous polyvinylpyrrolidone-based precursor solutions were selected for the electrospinning process. The presence of EVs in the electrospun samples was confirmed by transmission electron microscopy, flow cytometry, and confocal laser scanning microscope. The results indicate that the fibrous structure of the samples was preserved until the end of the 12-week storage period. Furthermore, regardless of the storage temperature (4 °C or room temperature), nanofibers and nanofiber-associated EVs were present throughout the experimental period. Incorporating EVs into a stable solid polymeric delivery base could preserve their stability; meanwhile, according to the characteristics of the polymer, their targeted and controlled release can be achieved.

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of “gold dust” cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.

This study aimed to summarize the screened articles on antibiotic shortages, compare them with the Hungarian Health Authority database, and identify the overlapping substances in shortages and handling practices. A systematic analysis was conducted using the provided keywords to filter out appropriate studies and incorporate them into this review. The studies were searched in the following databases: Reaxys, PubMed, Ovid, ScienceDirect, and Embase. The search time interval was 2000–2023, with the following keywords used: “antibiotic”, “shortage”, and “in clinic”. The shortage data for Hungary were collected and integrated within the specified timeframe. This was achieved through a comprehensive screening method to ensure comparability between the data from the literature review and the database. Based on the comparison, we have identified two groups of ingredients, the overlapping and not-overlapping ingredients. The mitigation practices were also categorized and evaluated to recommend good shortage management practices for Hungarian decision-makers and healthcare professionals. Our key conclusion was to enhance a shortage risk-based approach, including the legislative, health authority, and healthcare professionals responsible for therapeutic protocol and procuring or producing the necessary product. A widely approved shortage risk-based framework should be created to mitigate the impacts, including communication protocols, individual therapy planning, compounding of magistral products, and antimicrobial stewardship programs. The most common mitigation strategy is the substitution with available alternatives, but besides, a good understanding and implementation of antimicrobial stewardship programs is also crucial.

In this review, an extensive analysis of dry powder inhalers (DPIs) is offered, focusing on their characteristics, formulation, stability, and manufacturing. The advantages of pulmonary delivery were investigated, as well as the significance of the particle size in drug deposition. The preparation of DPI formulations was also comprehensively explored, including physico-chemical characterization of powders, powder processing techniques, and formulation considerations. In addition to manufacturing procedures, testing methods were also discussed, providing insights into the development and evaluation of DPI formulations. This review also explores the design basics and critical attributes specific to DPIs, highlighting the significance of their optimization to achieve an effective inhalation therapy. Additionally, the morphology and stability of 3 DPI capsules (Spiriva, Braltus, and Onbrez) were investigated, offering valuable insights into the properties of these formulations. Altogether, these findings contribute to a deeper understanding of DPIs and their development, performance, and optimization of inhalation dosage forms.

Assessing the attitudes of diabetic patients towards community-pharmacy services and determining the demand for new services could help monitor and evaluate the therapeutic response. This study aimed to evaluate type 2 diabetes patients’ satisfaction regarding pharmacy care in community pharmacies and shed a light on the reasons for diabetic patients’ non-adherence to treatments. An online survey was conducted on a random sample of patients (n = 196) at the national Diabetes Centre in Latakia, Syria, from April to November 2022. The questionnaire consisted of four primary parts: (1) demographic characteristics of responders, (2) patients’ therapeutic behaviors, (3) diabetes knowledge, and (4) the general level of satisfaction with pharmacy diabetes services. The data were analyzed using descriptive analysis. Around 89% of respondents were satisfied with the information provided by community pharmacists. The patients’ non-adherence showed a maximum as a function of the number of concomitantly taken medicines, which indicated that in most serious cases patients’ adherence was increasing. Overall, most patients were delighted with community pharmacists’ expertise and pharmacy services. This positive image allows pharmacists to expand their duties as healthcare providers in diabetes care, and increase the patient therapeutic adherence by performing a reconciliation of the patient’s medicines, which involves reviewing all patients’ drugs and identifying realistic solutions to their adherence issues.

It is well known that one of the most accessible health providers are community pharmacists; hence, their role in sanitarian programs should not be neglected. Although they were not present in the first pilot trial of the Hungarian Health Planning Application (HHPA) made by the National Healthcare Services Center, they were involved in the latter phases of the personal health planning program. The aim was the detailed assessment of the HHPA, with regard to the newly introduced online form. The HHPA is a software designed to identify health risks and help in the health planning and management of the risks. The present study was started in the 2016/2017 academic year, and the enrollment of citizens was carried out by resident pharmacists, who had received additional training on the software and primary (and tertiary) prevention. The resident pharmacists also filled two opinion survey questionnaires, one at the beginning of the study and one after the study period. Seventy-five pharmacists enrolled 594 citizens. At the 190 participants who enrolled by online application, the drop-out rate was similar to the personal way. The main four risks that were identified in the study were the risk of an inactive lifestyle (47.8%), weight problems (38.7%), risk of diabetes mellitus (26.9%), and cardiovascular risks (25.3%). About the project, the majority of the pharmacists thought that it was a useful project. Highlighted supporting factors were colleges in the pharmacies that were very encouraging; however, factors such as long risk-assessment or the non-cooperation of the other healthcare providers were discouraging. The personal health planning program is a favorable initiative for identifying health risks and determining health plans. Furthermore, the used software seems to be same effective as personal way, but more suitable in the present pandemic situation.

The poor ocular bioavailability of melatonin (MEL) limits the therapeutic action the molecule could exert in the treatment of ocular diseases. To date, no study has explored the use of nanofiber-based inserts to prolong ocular surface contact time and improve MEL delivery. Here, the electrospinning technique was proposed to prepare poly (vinyl alcohol) (PVA) and poly (lactic acid) (PLA) nanofiber inserts. Both nanofibers were produced with different concentrations of MEL and with or without the addition of Tween® 80. Nanofibers morphology was evaluated by scanning electron microscopy. Thermal and spectroscopic analyses were performed to characterize the state of MEL in the scaffolds. MEL release profiles were observed under simulated physiological conditions (pH 7.4, 37 °C). The swelling behavior was evaluated by a gravimetric method. The results confirmed that submicron-sized nanofibrous structures were obtained with MEL in the amorphous state. Different MEL release rates were achieved depending on the nature of the polymer. Fast (20 min) and complete release was observed for the PVA-based samples, unlike the PLA polymer, which provided slow and controlled MEL release. The addition of Tween® 80 affected the swelling properties of the fibrous structures. Overall, the results suggest that membranes could be an attractive vehicle as a potential alternative to liquid formulations for ocular administration of MEL.

The vertical diffusion cell is an in vitro laboratory device for the study of drug release and permeation of semi-solid topical formulations and topical patches. Both static and dynamic versions of the diffusion cell are used in practice, the operation of which can be automated. The device is available at a reasonable cost for smaller, mainly transdermal patches, the amount of sampling fluid is replenished at the same time as the sample, in the same amount as the amount sampled without automation of the system, and simultaneous replenishment of acceptor fluid by hydrostatic pressure helps keeping the acceptor chamber bubble-free.

The aims of this systematic review are to explore the possibilities of using the positron annihilation lifetime spectroscopy (PALS) method in the pharmaceutical industry and to examine the application of PALS as a supportive, predictive method during the research process. In addition, the review aims to provide a comprehensive picture of additional medical and pharmaceutical uses, as the application of the PALS test method is limited and not widely known in this sector. We collected the scientific literature of the last 20 years (2002–2022) from several databases (PubMed, Embase, SciFinder-n, and Google Scholar) and evaluated the data gathered in relation to the combination of three directives, namely, the utilization of the PALS method, the testing of solid systems, and their application in the medical and pharmaceutical fields. The application of the PALS method is discussed based on three large groups: substances, drug delivery systems, and medical devices, starting with simpler systems and moving to more complex ones. The results are discussed based on the functionality of the PALS method, via microstructural analysis, the tracking of ageing and microstructural changes during stability testing, the examination of the effects of excipients and external factors, and defect characterization, with a strong emphasis on the benefits of this technique. The review highlights the wide range of possible applications of the PALS method as a non-invasive analytical tool for examining microstructures and monitoring changes; it can be effectively applied in many fields, alone or with complementary testing methods.

Conductive education originated in Hungary in the late 1940s as a unique form of education and rehabilitation for children with neurological motor disorder. The basic idea of András Pető's unique system (conductive pedagogical system) was that our nervous system, despite being damaged, has reserved the possibility of building new connections, which can be mobilised by the proper control of the learning-teaching process. Based on the accessible documents, the paper provides a comprehensive overview of the sageuse implemented by András Pető, the internationally acknowledged founder of conductive education. Besides the traditional application of sage in conductive education it also reviews the known phytotherapeutic effects and recent clinical trials. The available clinical trials confirm the successful traditional application of sage extracts in conductive education and provide a promising starting point for evidence-based studies regarding its application in conductive education.

Abstract Background Pharmaceutical care is the pharmacist’s contribution to the care of individuals to optimize medicines use and improve health outcomes. The primary tool of pharmaceutical care is medication review. Defining and classifying Drug-Related Problems (DRPs) is an essential pillar of the medication review. Our objectives were to perform a pilot of medication review in Hungarian community pharmacies, a DRP classification was applied for the first time. Also, our goal was the qualitative and quantitative description of the discovered DRPs, and of the interventions for their solution in order to prove the safety relevance of the service and to map out the competence limits of GPs and community pharmacists to drug therapy. Methods The project took place in Hungarian community pharmacies. The study was performed with patients taking vitamin K antagonist (VKA) and/or ACE inhibitor and NSAID simultaneously (ACEI-NSAID). 61 pharmacists and 606 patients participated in the project. Pharmacists reviewed the medication for 3 months and the classification of DRPs was performed (category of DRP1 – DRP6). Patient data were statistically analyzed. Results Patients consumed on average 7.9 ± 3.1 medications and other products. 571 DRPs were detected in 540 patients, averaging 1.06 DRPs per patient (SD = 1.07). The highest frequency category was DRP5 (non-quantitative safety problem; 51.0%). The most common root cause was an interaction (42.0%) and non-adherence (19.4%.). The most commonly used intervention was education (25.4%) and medication replacement by the pharmacist (20.1%). The changing of the frequency and dosage in any direction were negligible. Conclusions Patients are struggling with many DRPs that can be assessed and categorized by this system and which remain unrecognizable without pharmacists. Further projects need to be developed to assist in the development of physician-pharmacist cooperation and the widespread dissemination of pharmaceutical care.

Several applications of nanofiber-based systems are based on their corresponding functionality-related properties, which often cannot be satisfied by a fiber web with a monolithic structure because of the various physicochemical properties and amounts of embedded compounds. Therefore, one of the main directions in the development of fiber systems is creating core–shell type complex fiber structures that can provide application-specific properties to the fiber matrix. The present study aimed to formulate levocetirizine-loaded core–shell type hydrophilic polymer-based fibrous systems. The core phase contained the antihistamine levocetirizine, while the permeation enhancer (Na-taurocholate), the local pH regulator (citric acid), and the cyclodextrin used as a taste masking agent were included in the shell phase of the fibrous formulation. Scanning electron microscopy images indicated that a randomly oriented homogeneous fibrous structure was obtained, while the Raman mapping and chemometric analysis confirmed the partially formed core–shell structure. A fast release rate of the antihistamine drug from the complex structural fibrous system was obtained (within 1 min complete dissolution can be observed) due to its increased surface area to volume ratio and its more favorable wettability properties, which consequently allows for more erosion. The masking properties against the unpleasant bitter taste of API of the formulated complex nanostructure were confirmed by the results of the electronic tongue. The formulated complex nanostructure enabled fast and complete release of the API, providing a potential enhancement in the rate and extent of absorption while masking the unpleasant taste of levocetirizine, which has a high impact on the patient adherence. All in all, the results show that the developed orally dissolving fibrous web formulation can be a potential alternative to the commercially available orally disintegrating tablets.

ObjectiveThe study examined the Drug-Related Problems (DRPs) of patients with polypharmacy in 78 Hungarian community pharmacies, especially the interaction risks in terms of their clinical severity. Also, the objective was to analyze pharmacists' interventions to solve the identified interaction risks.MethodologyThe research was carried out in the framework of the training of specialist pharmacists at Semmelweis University, with the participation of 78 graduated pharmacists with the collaboration of 98 GPs. A total of 755 patients participated in pharmaceutical counseling which meant a medication review process. DRPs were uniformly categorized and the interventions were recorded by pharmacists, while a detailed analysis of interaction risks was performed by authors.ResultsA total of 984 DRPs were registered. The most common category of DRPs was the "non-quantitative safety problems" (62.6%). Interaction risk was the most common cause of DRPs (54.0%). The highest proportion of interaction risks were between two prescription drugs (66.7%). In 30.7% of interaction risks' cases, there was not known negative outcome. In contrast, it was recommended to modify the therapy in 14.9% of interaction risks. Acetylsalicylic acid (22.8%), acenocoumarol (17.7%), and diclofenac (13.9%) were the most common active substances which caused serious interaction risks. A total of 599 pharmacist interventions were used to solve the 531 interaction risks. Pharmacists notified the GPs about the problem in 28.4% of cases and they intervened without the GP in 63.1% of cases, most often with patient education (27.4%).ConclusionMedication review by community pharmacists is required for the safe medicine using of patients with polypharmacy, as a significant number of DRPs have been recorded. The incidence of interaction risks stood out. It is essential to develop a pharmaceutical guideline to properly classify the clinical relevance of interaction risks (e.g. according to high-risk active substances) and to increase the collaboration with GPs.

Objectives The research aimed to support the effectiveness and necessity of the communication training and methodology introduced in the postgraduate pharmacy training and community pharmacy practice in Hungary.Design Two cross-sectional questionnaire surveys before and after the introduction of a methodological recommendation.Setting 69 Hungarian community pharmacies.Participants The study included 333 pharmacists and pharmacy technicians from community pharmacies, 890 and 847 patients (over 18 who bought their prescribed medication) at the beginning and the end of the project, respectively.Interventions A 3-day postgraduate health literacy-focused communication training followed by the ‘Train the trainer’ teaching method at pharmacies, then the introduction of the learnt methodology using uniform information materials and a communication checklist.Primary and secondary outcome measures Primary: total score of the staff and patient questionnaires and the change in score due to the intervention, total and for each question. Secondary: the differences between sexes, age groups, marital statuses, educational attainments and types of settlement.Results The mean score of the preintervention patient group was 64.07% which increased to 72.72% by the end of the project (p

Background: Preventing infectious diseases has become particularly relevant in the past few years. Therefore, antiseptics that are harmless and insusceptible to microbial resistance mechanisms are desired in medicine and public health. In our recent work, a poly(ethylene oxide)-based nanofibrous mat loaded with sodium chlorite was formulated. Methods: We tested the chlorine dioxide production and bacterial inactivation of the fibers in a medium, modeling the parameters of human exhaled air (ca. 5% (v/v) CO2, T = 37 °C, RH > 95%). The morphology and microstructure of the fibers were investigated via scanning electron microscopy and infrared spectroscopy. Results: Smooth-surfaced, nanoscale fibers were produced. The ClO2-producing ability of the fibers decreased from 65.8 ppm/mg to 4.8 ppm/mg with the increase of the sample weight from 1 to 30 mg. The effect of CO2 concentration and exposure time was also evaluated. The antibacterial activity of the fibers was tested in a 24 h experiment. The sodium-chlorite-loaded fibers showed substantial antibacterial activity. Conclusions: Chlorine dioxide was liberated into the gas phase in the presence of CO2 and water vapor, eliminating the bacteria. Sodium-chlorite-loaded nanofibers can be sources of prolonged chlorine dioxide production and subsequent pathogen inactivation in a CO2-rich and humid environment. Based on the results, further evaluation of the possible application of the formulation in face-mask filters as medical devices is encouraged.

In this study, scaffolds were prepared via an electrospinning method for application in oral cavities. The hydrophilicity of the fiber mesh is of paramount importance, as it promotes cell spreading; however, the most commonly used polyvinyl alcohol (PVA) and other hydrophilic fiber meshes immediately disintegrate in aqueous media. In contrast, the excessive hydrophobicity of the scaffolds already inhibits cells adhesion on the surface. Therefore, the hydrophilicity of the fiber meshes needed to be optimized. Scaffolds with different polyvinyl alcohol (PVA)/chitosan/citric acid ratios were prepared. The addition of chitosan and the heat initiated cross-linkage of the polymers via citric acid enhanced the scaffolds’ hydrophobicity. The optimization of this property could be followed by contact angle measurements, and the increased number of cross-linkages were also supported by IR spectroscopy results. The fibers’ physical parameters were monitored via low-vacuum scanning electron microscopy (SEM) and atomic force microscopy (AFM). As biocompatibility is essential for dental applications, Alamar Blue assay was used to prove that meshes do not have any negative effects on dental pulp stem cells. Our results showed that the optimization of the fiber nets was successful, as they will not disintegrate in intraoral cavities during dental applications.

Currently, ocular inserts and nanoparticles have received much attention due to the limited bioavailability of conventional eye preparations and the toxicity problems of systemic drug administration. The current systematic review aims to present recent studies on the use of electrospun nanofiber-based ocular inserts to improve the bioavailability of drugs used for different ophthalmic diseases. A systematic search was performed in PubMed, Ovid Medline, Web of Science, ScienceDirect, Scopus, Reaxys, Google Scholar, and Google Patents/Espacenet taking “drug-loaded”, “nanofibers”, and “ophthalmic inserts” and their equivalent terms as keywords. The search was limited to original and peer-reviewed studies published in 2011–2021 in English language. Only 13 out of 795 articles and 15 out of 197 patents were included. All results revealed the success of nanofiber-based ocular inserts in targeting and improved bioavailability. Ocular inserts based on nanofibers can be used as safe, efficient carriers for the treatment of anterior and posterior eye diseases.

Pharmaceutical compounding enables the preparation of unlicensed medicine to meet specific patient needs that do not have a licensed medicine available on the market. It must be performed in the best possible circumstance by certified pharmacists using validated standard operating procedures to obtain the highest quality medicinal product. The various spinning techniques provide drug delivery systems easily adapted to individual patient’s needs among the emerging technologies. The primary purpose of the present work was to introduce the prototype of a contact drawing device for the compounding of drug delivery systems for individual in-patient needs. The preliminary experiments resulted in oriented fibers of micrometer diameter range. The device can be placed in controlled conditions and could provide drug-loaded fibrous sheets for further treatments assuring the individual patient’s medicine need of the required quality.

Enzyme replacement therapies (ERT) have been of great help over the past 30 years in the treatment of various lysosomal storage disorders, including chronic pancreatitis and its common complication, exocrine pancreatic insufficiency. Research shows that difficulties in designing such drugs can be overcome by using appropriate additives and various enzyme immobilization techniques. Cyclodextrins (CDs) can be considered as a promising additive for enzyme replacement therapies, as they are known to enhance the activity of enzymes in a complex process due to their specific binding. In this study, we investigated the formulation of lipases (from Aspergillus oryzae and Burkholderia cepacia) paired with different cyclodextrins in poly(vinyl alcohol) (PVA) nanofibers by electrospinning technique. We examined the effect of the presence of cyclodextrins and nanoformulation on the lipase activity. The rheological and morphological characterizations of precursors and nanofibers were also performed using a viscometer as well as electron and Raman microscope. We found that by selecting the appropriate CD:lipase ratio, the activity of the investigated enzyme could be multiplied, and cyclodextrins can support the homogeneous dispersion of lipases inside the solid formula. In addition, the entrapment of lipases in PVA nanofibers led to a significant increase in activity compared to the preformulated precursor. In this way, the nanofibrous formulation of lipases combining CDs as additives can provide an efficient and sustainable possibility for designing novel solid medicines in ERT.

Recently, the electrospinning (ES) process has been extensively studied due to its potential applications in various fields, particularly pharmaceutical and biomedical purposes. The production rate using typical ES technology is usually around 0.01–1 g/h, which is lower than pharmaceutical industry production requirements. Therefore, different companies have worked to develop electrospinning equipment, technological solutions, and electrospun materials into large-scale production. Different approaches have been explored to scale-up the production mainly by increasing the nanofiber jet through multiple needles, free-surface technologies, and hybrid methods that use an additional energy source. Among them, needleless and centrifugal methods have gained the most attention and applications. Besides, the production rate reached (450 g/h in some cases) makes these methods feasible in the pharmaceutical industry. The present study overviews and compares the most recent ES approaches successfully developed for nanofibers’ large-scale production and accompanying challenges with some examples of applied approaches in drug delivery systems. Besides, various types of commercial products and devices released to the markets have been mentioned.

In our current research, sucrose palmitate (SP) was applied as a possible permeation enhancer for buccal use. This route of administration is a novelty as there is no literature on the use of SP in buccal mucoadhesive films. Films containing SP were prepared at different temperatures, with different concentrations of SP and different lengths of hydroxypropyl methylcellulose (HPMC) chains. The mechanical, structural, and in vitro mucoadhesive properties of films containing SP were investigated. Tensile strength and mucoadhesive force were measured with a device and software developed in our Institute. Positron annihilation lifetime spectroscopy (PALS) and X-ray powder diffractometry (XRPD) were applied for the structure analysis of the films. Mucoadhesive work was calculated in two ways: from the measured contact angle and compared with direct mucoadhesive work, which measured mucoadhesive force, which is direct mucoadhesion work. These results correlate linearly with a correlation coefficient of 0.98. It is also novel because it is a new method for the determination of mucoadhesive work.

Fenofibrate-loaded electrospun microfibrous sheets were prepared in an attempt to enhance the dissolution of the poorly soluble antihyperlipidemic agent and to improve its bioavailability. Physicochemical changes that appeared during the electrospinning process were monitored using a wide array of solid-state characterization techniques, including attenuated total reflectance Fourier-transformed infrared spectroscopy and positron annihilation lifetime spectroscopy, while fiber morphology was monitored via scanning electron microscopy. Dissolution studies carried out both in 0.025 M sodium dodecyl sulfate and in water revealed an immediate release of the active agent, with an approximately 40-fold release rate enhancement in water when compared to the micronized active agent. The dramatic increase in dissolution was attributed partially to the amorphous form of the originally crystalline active agent and the rapid disintegration of the electrospun microfibrous sheet due to its high surface area and porosity. The obtained results could pave the way for a formulation of the frequently used antihyperlipidemic agent with increased bioavailability.

Electrospun nanofibers were prepared from furosemide-containing hydroxypropyl cellulose and poly(vinylpyrrolidone) aqueous solutions using different solubility enhancers. In one case, a solubilizer, triethanolamine, was applied, while in the other case a pH-modifier, sodium hydroxide, was applied. Scanning electron microscopy (SEM) was carried out for morphological characterization of the fibers. The SEM images indicated similar mean diameter size of the two fibrous formulations. However, in contrast to the NaOH-containing fibers of normal diameter distribution, the triethanolamine-containing fibers showed approximately normal diameter distribution, possibly due to their plasticizing effect and the consequent slightly ribbon-like morphology. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), powder X-ray diffraction (XRD) and positron annihilation lifetime spectroscopy (PALS) were applied for microstructural characterization. The FTIR measurements confirmed that furosemide salt was formed in both cases. There was no sign of any crystallinity based on the XRD measurements. However, the PALS highlighted the differences in the average o-Ps lifetime values and distributions of the furosemide-loaded fibrous formulations. The two types of electrospun nanofibrous formulations containing amorphous furosemide salt showed similar macrostructures but different microstructural characteristics depending on the type of solubility enhancers, which lead to altered storage stability.

Aceclofenac-loaded poly(vinyl-pyrrolidone)-based nanofiber formulations were prepared by electrospinning to obtain drug-loaded orally disintegrating webs to enhance the solubility and dissolution rate of the poorly soluble anti-inflammatory active that belongs to the BCS Class-II. Triethanolamine-containing ternary composite of aceclofenac-poly(vinyl-pyrrolidone) nanofibers were formulated to exert the synergistic effect on the drug-dissolution improvement. The composition and the electrospinning parameters were changed to select the fibrous sample of optimum fiber characteristics. To determine the morphology of the nanofibers, scanning electron microscopy was used. Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) were applied for the solid-state characterization of the samples, while the drug release profile was followed by the in vitro dissolution test. The nanofibrous formulations had diameters in the range of few hundred nanometers. FT-IR spectra and DSC thermograms indicated the amorphization of aceclofenac, which resulted in a rapid release of the active substance. The characteristics of the selected ternary fiber composition (10 mg/g aceclofenac, 1% w/w triethanolamine, 15% w/w PVPK90) were found to be suitable for obtaining orally dissolving webs of fast dissolution and potential oral absorption.

3D printing is attracting considerable interest for its capacity to produce prototypes and small production runs rapidly. Fused deposit modeling (FDM) was used to produce polyvalent test plates for investigation of the physical, chemical, and in-vitro biological properties of printed materials. The polyvalent test plates (PVTPs) are poly-lactic acid cylinders, 14 mm in diameter and 3 mm in height. The polymer ester backbone was surface modified by a series of ramified and linear oligoamines to increase its hydrophilicity and introduce a positive charge. The chemical modification was verified by FT-IR spectroscopy, showing the introduction of amide and amine functions, and contact angle measurements confirmed increased hydrophilicity. Morphology studies (SEM, optical microscopy) indicated that the modification of PVTP possessed a planar morphology with small pits. Positron annihilation lifetime spectroscopy demonstrated that the polymeric free volume decreased on modification. An MTT-based prolonged cytotoxicity test using Caco-2 cells showed that the PVTPs are non-toxic at the cellular level. The presence of surface oligoamines on the PVTPs reduced biofilm formation by Candida albicans SC5314 significantly. The results demonstrate that 3D printed objects may be modified at their surface by a simple amidation reaction, resulting in a reduced propensity for biofilm colonization and cellular toxicity.

Furosemide loaded electrospun fibers were prepared for buccal administration, with the aim of improving the oral bioavailability of the poorly soluble and permeable crystalline drug, which can be achieved by the increased solubility and by the circumvention of the intensive first pass metabolism. The water soluble hydroxypropyl cellulose (HPC) was chosen as a mucoadhesive polymer. In order to improve the electrospinnability of HPC, poly (vinylpyrrolidone) (PVP) was used. During the experiments, the total polymer concentration was kept constant at 15% (w/w), and only the ratio of the two polymers (HPC-PVP = 5:5, 6:4, 7:3, 8:2, 9:1) was changed. A combination of rheological measurements with scanning electron microscopic morphological images of electrospun samples was applied for the determination of the optimum composition of the gels for fiber formation. The crystalline–amorphous transition of furosemide was tracked by Fourier transform infrared spectroscopy. A correlation was found between the rheological properties of the polymer solutions and their electrospinnability, and the consequent morphology of the resultant samples. With decreasing HPC ratio of the system, a transition from the spray-dried droplets to the randomly oriented fibrous structures was observed. The results enable the determination of the polymer ratio for the formation of applicable quality of electrospun fibers.