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Abstract: Stability, defined as the reproducible behavior of a device upon its storage, is an important issue in pharmaceutical formulation. Silica xerogels obtained through the sol–gel route are relatively new as matrices for the controlled release of drugs. In some cases, it was observed that their behavior changes upon storage, so that they cannot always be defined as “stable”. This occurs especially when gel processing is performed at mild temperatures, a procedure that may have to be used to prevent degradation of the embedded drug. This work investigated the use of inorganic catalysts as potential xerogel stability inducers when gel curing by heating is not applicable. Three compounds known to accelerate sol–gel polymerization, namely ammonia, sodium fluoride and sodium carbonate, were introduced during the polymerization of low-temperature processed inorganic and organically modified gels, and the effect of each compound on xerogel stability and drug release was monitored. The use of carbonate leads to formulations with good retention properties, as opposed to ammonia and NaF, which lead to poorly retentive xerogels in accordance with their known ability to increase porosity. Ammonia was shown to be a poor stability promoter independently of gel composition, as opposed to fluoride and carbonate, which both displayed stabilizing properties in a dose-dependent manner. No correlation was found between xerogel stability and drug release properties. An attempt was also made to correlate stability data with polymerization rates and wet gel syneresis time evolution with the purpose of identifying one or more synthesis parameters that could act as stability predictors for pre-formulation studies. No correlation was found between stability and syneresis data. A similar trend in the curve of gel time vs. catalyst concentration was observed for the two stabilizing catalysts, which was different for the non-stabilizing ammonia. It was concluded that the trend of this curve could potentially provide an indicator of catalyst stabilizing efficacy. [Copyright &y& Elsevier]

Background: Vitamin D is a vital lipophilic vitamin that plays a pivotal role in calcium regulation, bone metabolism, and overall health. It is of the utmost importance to maintain appropriate serum levels of vitamin D from the moment of birth. The recommended daily intake for infants under the age of 12 months is 400 IU. In Europe, vitamin D is available in two forms: as a medicinal product and as a food supplement. The food supplement market is experiencing rapid growth, yet it is characterised by a lack of harmonised regulations, which may give rise to potential risks associated with their widespread use. While food supplements are typically regarded as safe, there is a potential for adverse effects, particularly when dosages are not properly managed., Case Report and Management: This report presents the case of a 22-month-old girl who developed nephrocalcinosis as a result of an overdose of vitamin D from a dietary supplement purchased online. The initial presentation was characterised by symptoms such as polydipsia, polyuria and decreased growth. It was subsequently revealed that the child had been receiving an excessively high dose of vitamin D, amounting to 25 times the recommended amount, over a period of seven months. Despite normal calcium levels and renal function at the time of presentation, ultrasound imaging revealed the presence of early-stage nephrocalcinosis. The treatment plan involved hospital admission, intravenous hydration, a thiazide diuretic, potassium citrate, and a low-calcium diet. The vitamin D supplement was ceased. Over the course of a year, the patient demonstrated recovery in growth and normalization of vitamin D levels, although nephrocalcinosis remained stable., Conclusion: This case study highlights the potential dangers of unsupervised vitamin D supplementation, emphasising the importance of healthcare professionals exercising vigilance in prescribing and advising on vitamin D use, particularly in children. Furthermore, it underscores the necessity of establishing a database to track long-term outcomes in paediatric vitamin D intoxication cases, given the rarity of such incidents. This would facilitate the development of appropriate treatment protocols and provide valuable information to parents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Pizzini, Ossato, Realdon and Tessari.)

Objectives: The transplantation of human tissues is a greatly expanding field of medicine with unquestionable benefits that raise questions about safety, quality and ethics. Since 1 October 2019, the Fondazione Banca dei Tessuti del Veneto (FBTV) stopped sending thawed and ready to be transplanted cadaveric human tissues to hospitals. A retrospective analysis of the period 2016-2019 found a significant number of unused tissues. For this reason, the hospital pharmacy has developed a new centralised service characterised by thawing and washing human tissues for orthopaedic allografts. This study aims to analyse the hospital cost and benefit derived from this new service., Methods: Aggregate data relating to tissue flows were obtained retrospectively for the period 2016-2022 through the hospital data warehouse. All tissues arriving from FBTV for each year were analysed, dividing them according to the outcome (if used or wasted). The percentage of wasted tissues as well as the economic loss due to wasted allografts were analysed per year and trimester., Results: We identified 2484 allografts requested for the period 2016-2022. In the last 3 years of the analysis, characterised by the new tissue management of the pharmacy department, we found a statistically significant reduction in wasted tissues (p<0.0001) from 16.33% (216/1323) with a cost to the hospital of 176 866€ during the period 2016-2019 to 6.72% (78/1161) with a cost to the hospital of 79 423€ during the period 2020-2022., Conclusion: This study shows how the centralised processing of human tissues in the hospital pharmacy makes the procedure safer and more efficient, demonstrating how the synergy between different hospital departments, high professional skills and ethics can lead to a clinical advantage for patients and a better economic impact for the hospital., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Aiming to achieve light sedation via intranasal administration, this study showed that propofol (PPF) did not permeate across the rabbit nasal mucosa ex vivo from its marketed emulsion for injection., Experimental Approach: Dilution of the emulsion with methyl-β-cyclodextrin in saline solution increased propofol solubility in water and diffusion across the nasal epithelium., Key Results and Conclusion: Despite these positive effects of the cyclodextrin, the amount of PPF permeated was minimal in 3 h, exceeding the formulation residence time in the nose. These results highlight the key role of formulation and the need for innovation in solubility and transmucosal transport enhancement techniques to optimize drug delivery and therapeutic efficacy., Competing Interests: Conflict of interest : The authors declare that they have no known competing financial interests nor personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 by the authors.)

In recent years, integrated data analysis has proven to be a valuable method for investigating complex systems, whether artificial or natural. The integrated analytical approach allows the simultaneous integration of data acquired from different analytical techniques employed for the same sample at the same time, leading to an expansion of the amount of information available. Surface tensiometry is a technique that was recently introduced in the Integrated Analytical Approach for investigating pharmaceutical dosage forms for topical application. Therefore, studies of rheological characterization, release, and skin permeation can be integrated with surface tensiometry measurements to develop chemical and rheological-surface correlation models, providing a new method for the quality control and process control of semisolid preparations. In this context, the aim of this research is to validate the utility of surface tensiometry measurements in the Integrated Analytical Approach and utilize these data to gain insights into the structure-surface correlation. The preparations chosen for this study were a PEG-gel, a lipogel, and an O/W cream containing carnitine as a model drug. The formulations were characterized using rheological measurements and evaluated for their carnitine release performance. Furthermore, surface tensiometry measurements were performed to rapidly and noninvasively assess the influence of carnitine on the surface properties of the semisolid preparations investigated. Our work demonstrated a close correlation between surface energy and structural data, showing the importance of surface tensiometry contribution in the noninvasive and rapid evaluation of the presence of carnitine in semisolid formulations.

Musculoskeletal allografts represent an important practice in orthopedic surgeries and the demand for them has been growing. For this reason, in order to reduce clinical risk and to more efficiently manage the increase of allograft usage and also to optimize timing of the surgeries, the thawing and washing processes with aseptic technique were centralized in the department of Hospital Pharmacy. This study describe the design and execution of an adapted Media Fill Test (MFT) to demonstrate aseptic thawing and washing of allografts. For this specific and innovative setting, to better simulate the actual processing steps, a surrogate system was developed to simulate the tendon allograft. The aseptic technique of four operators was assessed and an initial performance validation and the first revalidation were described. All MFT were completed successfully, with no observation of turbidity. The readapted MFT shown in this study can provide insight into this innovative and growing field to other health professionals who want to implement this service., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The two anti-epidermal growth factor receptor monoclonal antibodies (mAbs) cetuximab and panitumumab are the pillars for the treatment of EGFR-positive, KRAS wild-type metastatic colorectal cancers. However, stability data of these mAbs are generally missing or incomplete. Here, we report for the first time an orthogonal analysis of the stability of cetuximab (Erbitux®) and panitumumab (Vectibix®), either undiluted vial leftovers or saline dilutions in polyolefin/polyamide infusion bags. All samples were stored at 2-8 °C protected from light, according to their summary of product characteristics (SmPCs). Alternatively, opened vials and preparations were maintained at 25 °C for 15 h, and then stored again at 2-8 °C protected from light to mimic a temporary interruption of the cold chain. Vial leftovers proved stable up to 180 days when stored according to their SmPCs, while compounded preparations in infusion bags maintained their physiochemical, biological and microbiological stability up to 30 days. Additionally, no changes were detected up to 30 days for the same samples undergoing a thermal excursion. Our results provide additional rationale to the SmPCs, crucial especially in the case of reassignment and pre-preparation of bags. This information will allow hospitals to achieve significant cost savings, and better organization of the entire therapeutic process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Transdermal delivery of highly lipophilic molecules is challenging due to the strong barrier function of the skin. Vesicles with penetration enhancers are safe and efficient systems that could improve the transdermal delivery of non-psychoactive cannabinoids such as cannabidiol and desoxy-cannabidiol. In the last decades, research interest in desoxy-cannabidiol as a potent drug with anti-nociceptive properties has risen. Still, its scarce market availability poses a limit for both research and clinical applications. Therefore, it is necessary to improve the synthesis to produce sufficient amounts of desoxy-cannabidiol. Moreover, also the formulation aspects for this drug are challenging and require to be addressed to meet an efficient delivery to the patients., Objective: This work aimed to develop innovative phospholipid-based vesicles with propylene glycol (PG), oleic acid (OA), or limonene as edge activators, for the transdermal delivery of highly lipophilic drugs such as non-psychoactive cannabinoids. In particular, desoxy-cannabidiol was selected thanks to its anti-nociceptive activity, and its synthesis was improved enhancing the stereoselectivity of its synthon's production., Methods: Desoxy-cannabidiol was synthesized by Lewis acid-mediated condensation of p-mentha-2,8-dien- 1-ol and m-pentylphenol, improving the stereoselectivity of the first synthon's production. Transethosomes containing 20-50% w/w PG, 0.4-0.8% w/w OA, or 0.1-1% w/w limonene were optimized and loaded with cannabidiol or desoxy-cannabidiol (0.07-0.8% w/w, 0.6-7.0 mg/mL). Ex-vivo studies were performed to assess both the skin permeation and accumulation of the cannabinoids, as well as the penetration depth of fluorescein- loaded systems used as models., Results: An enantioselective bromination was added to the pathway, thus raising the production yield of pmentha- 2,8-dien-1-ol to 81% against 35%, and the overall yield of desoxy-cannabidiol synthesis from 12% to 48%. Optimized transethosomes containing 0.6 mg/mL cannabinoids were prepared with 1:10 PG:lipid weight ratio, 0.54 OA:lipid molar ratio, and 0.3 limonene:lipid molar ratio, showing good nanometric size (208 ± 20.8 nm - 321 ± 26.3 nm) and entrapment efficiency (> 80%). Ex-vivo tests showed both improved skin permeation rates of cannabinoids (up to 21.32 ± 4.27 μg/cm2 cannabidiol), and skin penetration (depth of fluorescein up to 240 μm, with PG)., Conclusion: Desoxy-cannabidiol was successfully produced at high yields, and formulated into transethosomes optimized for transdermal delivery. Loaded vesicles showed improved skin penetration of desoxy-cannabidiol, cannabidiol and a lipophilic probe. These results suggest the potential of these carriers for the transdermal delivery of highly lipophilic drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Several natural remedies are used in the Traditional Persian Medicine (TPM) to prevent dementia, but their efficacy is debated. In this work, an improved "Safoof-e-Nesyān" formulation described in the "Qarābādin-e-Azam" pharmacopoeia was developed, and its chemical composition and antioxidant and anti-cholinesterase properties were assessed. The formulation contains a mixture (FM) of Cinnamomum cassia (CC), C. verum (CV), Pistacia lentiscus (PL), Rheum palmatum (RP), Syzygium aromaticum (SA), and Zingiber officinalis (ZO) powdered plants. Its total phenolic content is 110.45 mg GAE/g, while the total flavonoid content is 6.28 mg RE/g. 66 secondary metabolites (mainly tannins, flavonoids, anthraquinones, and gingerols) were identified by UPLC-QToF-MS analysis. FM exerts antioxidant effects by scavenging radicals, and by reducing and chelating metals such as Mb, Cu and Fe. The anticholinesterase activity of one gram of the FM equals that of 3.60 mg of the reference drug galantamine, on both acetyl- and butyryl-cholinesterase. Correlations between specific compounds and bioactivities were highlighted by multivariate analysis of data: lyoniresinol 9'-glucoside strongly correlates with antiradical activities on DPPH and ABTS and reducing activity on Cu, and with anti-AChE effects. Most of the identified flavonoids and the ellagic acid derivatives positively correlate with the reducing activity on Fe and Mb, and with anti-BChE effects. Finally, a tablet formulation of the FM was developed, and its physical properties were preliminarily assessed. Overall, our results indicate that the FM may be a useful natural remedy for dementia, although further safety and efficacy assessments in vivo are required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: On 21 December 2020 the European Commission granted conditional marketing authorisation in the European Union for the anti-COVID-19 mRNA vaccine Bnt162b2 (Comirnaty, Pfizer/BioNTech). The main endpoint of this epidemiological, observational, prospective and monocentric study was to identify the number, types, and severity of adverse events following immunisation that occurred in subjects who had been previously infected with COVID-19, and in those who had not, after vaccination with Comirnaty, and to compare the two groups of subjects looking at events that occurred within a month after the first and the second dose., Methods: Data were gathered by a questionnaire. The results included the responses of all healthcare workers (2030) of the IRCCS Sacro Cuore Don Calabria Hospital (Italy) vaccinated between 1st January and 28th February 2021. Adverse effects of the vaccine were reported after the first and the second doses., Results: There was a statistically significant increase (p<0.001, χ 2 =35.60) in participants who experienced some side-effects after receiving the first dose of the vaccine and who had previously been infected with the coronavirus, compared with participants who had not previously been infected. 46.76% (136) of the participants who had previously been infected experienced some side-effects after the first dose of vaccine, and 63.23% (184) experienced some side-effects after the second dose, compared with 29.15% (507) after the first dose and 70.79% (1231) after the second dose in those who had not been previously infected. The number of participants who experienced side-effects after the second dose and had previously been infected was significantly lower compared with participants who had not previously been infected (p=0.0094, χ 2 =6.743)., Conclusions: Most of the side-effects identified in this trial were also reported by the manufacturer and the US Food and Drug Administration. Active surveillance should always continue to constantly check the vaccine's risk/benefit ratio over time., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Preparation of injectable anticancer drugs in hospital pharmacies is a high-risk activity that requires a proper risk assessment (RA) and quality assurance system (QAS) to ensure both a decrease in risk associated with chemotherapy compounding and high quality of the final product, especially in terms of its microbiological stability., Methods: At the centralized compounding unit (UFA) of the Italian Hospital IOV-IRCCS, a quick and deductive method was applied to evaluate the "added value" provided by each prescribed preparation, and its RA was calculated applying a formula that integrates different pharmacological, technological and organizational aspects. According to specific RA range values, the preparations were divided into different risk levels, in order to determine the QAS to be adopted, according to the Italian Ministry of Health guidelines, whose adherence was meticulously evaluated through a specific self-assessment procedure. A review of the scientific literature was carried out to integrate the risk-based predictive extended stability (RBPES) of drugs with data concerning their physiochemical and biological stability., Results: Based on the self-assessment comprising all microbiological validations of the working area, personnel and products, the microbiological risk level within the IOV-IRCCS' UFA was defined through the creation of a transcoding matrix, conferring a microbiological stability to preparations and vial leftovers of a maximum of 7 days. The calculated RBPES were successfully integrated with stability data from the literature, leading to the drafting of a stability table of drugs and preparations in use in our UFA., Conclusions: Our methods allowed us to perform an in-depth analysis of the highly specific and technical process of anticancer drug compounding in our UFA, ensuring a certain grade of quality and safety to preparations, especially in terms of microbiological stability. The resulting RBPES table represents an invaluable tool with positive repercussions at organizational and economic levels.

Introduction: Bias in dissemination and reporting of clinical research findings has an impact on the pooled summary utilised to produce clinical-therapeutic guidelines and recommendations. This analysis aims to evaluate the dissemination and reporting biases of interventional and observational studies conducted in the setting of the Local health authority of Verona (Aulss). The possible correlation between both biases and profit versus no-profit sponsors was also evaluated., Methods: Verona's Aulss studies completed in the period 01.01.2014-31.01.2021 were extracted from the Clinical study register of the Veneto Region and any form of results' dissemination was identified and compared with the original protocol. Identified studies were stratified by profit or no-profit sponsor and results compared using the Chi-Square test., Results: 67 studies (29 profit; 38 non-profit) were included in this analysis. 58.2% of the studies (n=39/67) reports at least one type of findings' dissemination, for 22.4% data-analysis or publication is in progress, while 19.4% has not been published. Regarding the evaluation on reporting bias, 36 of the 39 published studies were considered (n=19 profit; n=17 non-profit): 64% (23/36) showed inconsistencies between the results reported in the manuscript and the protocol. The number of non-compliant profit studies (n=15/19; 79%) was statistically higher than the compliant ones [n=8/17; 47%; (p=0.049; χ2=3.845)]., Discussion: This study highlights that findings' dissemination occurs for the majority of the studies evaluated and that the odds of selective reporting are higher for industry funded studies than for publicly funded studies, affecting the quality of the research.

We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of neuroendocrine tumors (NETs). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus databases. The following words, coupled two by two, were used: 68 Ga-DOTATOC; 68 Ga-DOTATATE; 68 Ga-DOTANOC; 99m Tc-EDDA/HYNIC-TOC; 64 Cu-DOTATATE; and 111 In-DTPA-octreotide. Moreover, a second-step search strategy was adopted by using the following combined terms: "Somatostatin receptor imaging,"; "Somatostatin receptor imaging" and "Functional,"; "Somatostatin receptor imaging" and "SPECT,"; and "Somatostatin receptor imaging" and "PET". Eligible criteria were: (1) original articles focusing on the clinical application of the radiopharmaceutical agents in NETs; (2) original articles in the English language; (3) comparative studies (head-to-head comparative or matched-paired studies). Editorials, letters to the editor, reviews, pictorial essays, clinical cases, or opinions were excluded. A total of 1077 articles were found in the three electronic databases. The full texts of 104 articles were assessed for eligibility. Nineteen articles were finally included. Most articles focused on the comparison between 111 In-DTPA-Octreotide and 68 Ga-DOTATOC/TATE. Few papers compared 64 Cu-DOTATATE and 68 Ga-DOTATOC/TATE, or SPECT tracers. The rates of true positivity were 63.7%, 58.5%, 78.4% and 82.4%, respectively, for 111 In-DTPA-Octreotide, 99m Tc-EDDA/HYNIC-TOC, 68 Ga-DOTATATE/TOC and 64 Cu-DOTATATE. In conclusion, as highly expected, PET tracers are more suitable for the in vivo identification of NETs. Indeed, in comparative studies, they demonstrated a higher true positive rate than SPECT agents.

The purpose of this narrative review was to assess the use of nanoparticles (NPs) to deliver radionuclides to targets, focusing on systems that have been tested in pre-clinical and, when available, clinical settings. A literature search was conducted in PubMed and Web of Science databases using the following terms: "radionuclides" AND "liposomes" or "PLGA nanoparticles" or "gold nanoparticles" or "iron oxide nanoparticles" or "silica nanoparticles" or "micelles" or "dendrimers". No filters were applied, apart from a minimum limit of 10 patients enrolled for clinical studies. Data from some significant studies from pre-clinical and clinical settings were retrieved, and we briefly describe the information available. All the selected seven classes of nanoparticles were highly tested in clinical trials, but they all present many drawbacks. Liposomes are the only ones that have been tested for clinical applications, though they have never been commercialized. In conclusion, the application of NPs for imaging has been the object of much interest over the years, albeit mainly in pre-clinical settings. Thus, we think that, based on the current state, radiolabeled NPs must be investigated longer before finding their place in nuclear medicine.

The aim of this review was to assess recent progress in targeted radionuclide tumor therapy, focusing on the best delivery strategies. A literature search was conducted in PubMed, Web of Science, and Scopus using the terms "radionuclides", "liposomes", "avidin-biotin interaction", "theranostic", and "molecular docking". The 10 year filter was applied, except for the avidin-biotin interaction. Data were retrieved from both preclinical and clinical settings. Three targeting strategies were considered: pretargeting, liposomes, and ligands. Pretargeting can be achieved by exploiting the avidin-biotin interaction. This strategy seems very promising, although it has been investigated mainly in resectable tumors. Radiolabeled liposomes have attracted new interest as probes to identify the most suitable patients for treatment with liposomal formulations of common chemotherapeutics. The use of ligands for the delivery of radiotherapeutics to a specific target is still the most appealing strategy for treating tumors. The most appropriate ligand can be identified by virtually simulating its interaction with the receptor. All strategies showed great potential for use in targeted radionuclide therapy, but they also have numerous drawbacks. The most promising option is probably the one based on the use of new ligands.

Recently, the atrial fibrillation treatment guidelines have been updated to now recommend Non-vitamin K antagonist oral anticoagulants (NOACs) as the preferred alternative to warfarin for systemic embolism and stroke prevention in patients with non-valvular atrial fibrillation. NOACs have major pharmacologic advantages over warfarin, although the most common complications are gastrointestinal bleeding and NOAC-induced nephropathy within 6 weeks after starting therapy, as several recent case-reports stated. We are reporting for the first time a chronic delayed adverse reaction (regularly reported to Authorities) observed in an 82-year-old woman 27 months after starting dabigatran (110 mg twice a day), characterized by concomitant gastrointestinal bleeding and nephropathy. Idarucizumab administration immediately improved both bleeding and renal parameters. Moreover, we are going to highlight the importance of the compliance, the adherence to the therapeutic plan and the supervision of the Hospital Pharmacy on drug prescriptions. In fact in our case, dabigatran was firstly prescribed by the neurologist and delivered by the hospital pharmacy, but the patient continued the treatment for 27 months, prescribed by general practitioner without any laboratory control. This lack of supervision certainly contributed to the onset of the adverse reaction reported., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Silver-111 ( 111 Ag, t 1/2  = 7.47 d) is a β - emitter suitable for targeted cancer therapy due to favourable decay properties. The production of no-carrier added 111 Ag via Isotope Separation On-Line (ISOL) technique is being investigated at the Legnaro National Laboratories of the Italian Institute of Nuclear Physics (ISOLPHARM project). Stable Cadmium-111 ( 111 Cd) is co-produced as isobaric contaminant, hence a chemical separation process must be developed to selectively harvest 111 Ag. In this study, a chromatographic procedure employing the commercially available CL resin was investigated by using stable Ag + and Cd 2+ . Results indicate that CL resin allows to efficiently separate Ag + from Cd 2+ and recover the former with high yields., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Research in the field of radiopharmaceuticals is increasingly promoted by the widespread and growing interest in applying nuclear medicine procedures in both disease diagnosis and treatment. The production of radionuclides of medical interest is however a challenging issue. Along with the conventional techniques other innovative approaches are being investigated and, among those, the ISOLPHARM project is being developed at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro). Such technique foresees the employment of the SPES ISOL facility to produce isobarically pure Radioactive Ion Beams (RIBs), obtained thanks to electromagnetic mass separation and collected on appropriate substrates. The latter are successively recovered and dissolved, allowing thus the chemical separation and harvesting of the nuclides of interest, free from any isotopic contaminant. Although ISOLPHARM can be potentially employed for most of the routinely used medical radioisotopes, its innovation potential is better expressed considering its capability to provide carrier free unconventional nuclides, difficult to produce with state-of-art techniques, such as 111 Ag, a β - emitter potentially interesting for therapeutic applications. Thus, in the framework of ISOLPHARM, INFN supported a two-years experiment, called ISOLPHARM&#95;Ag, aimed at evaluating the feasibility of the production of a 111 Ag labelled radiopharmaceutical. The ISOL production yields are estimated by computing intensive Monte Carlo codes, that require an appropriate custom Information Technology infrastructure. The presented work is focused on the first part of the production chain including the capability to extract, ionize, and collect stable Ag beams with SPES technologies. MC calculations were used to estimate the expected 111 Ag in-target yields, whereas experiments with stable Ag were performed to test the ionization, transport and collection of Ag beams., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: In vitro hemolysis is the primary cause of sample/test rejection by the laboratory., Case Report: A 10-year-old, admitted with an asthma attack in the emergency-room, medicated with albuterol sulphate (intravenous bronchodilator that could induce hypokalemia), needed laboratory test monitoring. The physician prescribed the technical-nurse to perform blood sampling for: complete blood count, electrolytes, glucose, and blood gas analysis-within 30min after therapy. Samples were delivered to laboratory with a note "I had difficult to locate an appropriate access to perform the blood collection"., Laboratory Results: Glucose: 4.77 mmol/L. Complete blood count revealed discreet eosinophilia 0.13x10 9 /L, and thrombocytopenia 18x10 9 /L. However, platelet clumps were observed in peripheral blood smear. Blood gas analysis was unreported, laboratory informed that sample had micro clots.Electrolytes: laboratory did not report the results; sample hemolyzed. 0.9 g/L of free hemoglobin is the cut-off defined by the laboratory; the sample presented 2.3 g/L of free hemoglobin. 3.9 mmol/L of potassium was the unreported result vs 2.1 mmol/L in the new sample.Briefly, the laboratory technician was trained to hide potassium results on hemolyzed sample due to the potential overestimation. Even if the hemolyzed sample presented a potassium value close to the lower reference range value (3.5-5.1 mmol/L), reporting the potassium result could allow the physician starting proper therapy to revert the hypokalemia by albuterol sulfate., Conclusion: The laboratory should be aware of the clinical patient conditions and of the related physician needs, before hiding results. Therefore, both the laboratory and the clinic personnel should communicate in order to guarantee the patient safety., Competing Interests: *These graduation-students contributed equally to this work. Therefore, their names are listed in alphabetical order., (Copyright © 2020 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

Objectives: Traditionally, pharmacy ethics in Europe has held an insignificant place in the scheme of pharmaceutical education. We embraced the idea that bioethics should be an integral part of a pharmacist's education and professional practice, especially in hospital pharmacy where the concept of 'pharmaceutical care' should be revitalised to strengthen the broad-based and patient-oriented responsibilities of the clinical pharmacist., Methods: We decided to structure a bioethics course tailored to pharmacists who are specialising in hospital pharmacy. We first created a training network partnership between a university and a research hospital to integrate classroom teaching with skill-specific practical experience. Our course pilot project introduces, in two of the four years of the national specialty programme, general topics and practical bioethical issues., Results: A pilot course on ethics for the School of Specialisation in Hospital Pharmacy began at the Padua University in 2014. in February 2017 we contacted the same students again, asking them further questions about their experience. Several students asked to examine more cases and to deal with the few arguments that questioned them on an ethical level. On the whole, through the comments of trainees, the needs of those who are facing an unfamiliar subject, which is perceived as important, emerge., Conclusion: Even if we are aware that this is a pilot project and requires more data, dissemination of this experience into a wider network will help us to define an effective educational pathway in collaboration with other Specialty Schools of Hospital Pharmacy., Competing Interests: Competing interests: None declared.

Nowadays, personalized cancer therapy relies on small molecules, monoclonal antibodies, or antibody-drug conjugates (ADC). Many nanoparticle (NP)-based drug delivery systems are also actively investigated, but their advantage over ADCs has not been demonstrated yet. Here, using the Avidin-Nucleic-Acid-Nano-Assemblies (ANANAS), a class of polyavidins multifuctionalizable with stoichiometric control, we compare quantitatively anti-EGFR antibody(cetuximab)-targeted NPs to the corresponding ADC. We show that ANANAS tethering of cetuximab promotes a more efficient EGFR-dependent vesicle-mediated internalization. Cetuximab-guided ANANAS carrying doxorubicin are more cytotoxic in vitro and much more potent in vivo than the corresponding ADC, leading to 43% tumor reduction at low drug dosage (0.56 mg/kg). Advantage of cetuximab-guided ANANAS with respect to the ADC goes beyond the increase in drug-to-antibody ratio. Even if further studies are needed, we propose that NP tethering could expand application of the anti-EGFR antibody to a wider number of cancer patients including the KRAS-mutated ones, currently suffering from poor prognosis.

The ISOLPHARM (ISOL technique for radioPHARMaceuticals) project is dedicated to the development of high purity radiopharmaceuticals exploiting the radionuclides producible with the future Selective Production of Exotic Species (SPES) Isotope Separation On-Line (ISOL) facility at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (INFN-LNL). At SPES, a proton beam (up to 70 MeV) extracted from a cyclotron will directly impinge a primary target, where the produced isotopes are released thanks to the high working temperatures (2000 °C), ionized, extracted and accelerated, and finally, after mass separation, only the desired nuclei are collected on a secondary target, free from isotopic contaminants that decrease their specific activity. A case study for such project is the evaluation of the feasibility of the ISOL production of 64 Cu and 67 Cu using a zirconium germanide target, currently under development. The producible activities of 64 Cu and 67 Cu were calculated by means of the Monte Carlo code FLUKA, whereas dedicated off-line tests with stable beams were performed at LNL to evaluate the capability to ionize and recover isotopically pure copper.

The diffusion coefficient (also known as diffusivity) of an active pharmaceutical ingredient (API) is a fundamental physicochemical parameter that affects passive diffusion through biological barriers and, as a consequence, bioavailability and biodistribution. However, this parameter is often neglected, and it is quite difficult to find diffusion coefficients of small molecules of pharmaceutical relevance in the literature. The available methods to measure diffusion coefficients of drugs all suffer from limitations that range from poor sensitivity to high selectivity of the measurements or the need for dedicated instrumentation. In this work, a simple but reliable method based on time-resolved concentration measurements by UV-visible spectroscopy in an unstirred aqueous environment was developed. This method is based on spectroscopic measurement of the variation of the local concentration of a substance during spontaneous migration of molecules, followed by standard mathematical treatment of the data in order to solve Fick's law of diffusion. This method is extremely sensitive and results in highly reproducible data. The technique was also employed to verify the influence of the environmental characteristics (i.e., ionic strength and presence of complexing agents) on the diffusivity. The method can be employed in any research laboratory equipped with a standard UV-visible spectrophotometer and could become a useful and straightforward tool in order to characterize diffusion coefficients in physiological conditions and help to better understand the drug permeability process.