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ObjectivesRadiopharmaceuticals, since the discovery of the first medical application of radioactive isotope, have been essential therapeutics for the diagnosis and treatment of numerous diseases. Since the Directive 2001/83/EC entered in force, European regulatory authorities have established a harmonised framework to set quality requirements for the industrial production of radiopharmaceuticals. However, little is known about the harmonisation of extemporaneous preparation of radiopharmaceutical preparations (EPRPs) among European countries. In this context, this study aims to provide an overview of the national regulatory framework on the production of EPRPs of five European countries (i.e. UK, Spain, France, Germany and Italy).MethodsFive different national regulatory frameworks were compared based on the results of a literature search on electronic databases (i.e. PubMed, Google scholar).Key findingsUnlike industrially produced radiopharmaceuticals, the results highlighted that the regulatory framework on EPRPs is still not fully harmonised at the European level and many provisions are regulated by local national laws. Similarities and differences exist among the European countries, both regarding quality standards and educational courses the operators involved in the preparation of EPRPs have to attend.ConclusionsThe regulatory framework on the EPRPs is still not harmonised at the European level affecting the access to therapies of European citizens who are not equally guaranteed when an extemporaneous radiopharmaceutical has to be prepared to meet their needs.

The rising costs of new medicinal products are a challenge to the economic sustainability of national healthcare systems in ensuring patients' access to therapies. European Union (EU) and US legislators have provided regulatory pathways aimed at simplifying Marketing Authorization (MA) applications for new medicinal products in cases when safety and efficacy profiles can be derived from the data of already-marketed products. In this review, we discuss the different regulatory pathways towards the MA of new medicinal products containing old drug substances and intended to improve the therapeutic value of a treatment, to obtain a new therapeutic indication (drug repositioning), or to ensure the same therapeutic value of a reference product at lower costs.

Purpose To analyse the pattern of use and cost of antihypertensive drugs in new users in an Italian population, and explore the patient/treatment factors associated with the risk of therapy discontinuation. Patients and methods In this retrospective study, information was collected from a population-based electronic primary-care database. Persistence with medication use 1 year from therapy initiation was evaluated for each user using the gap method. Each new user was classified according to his/her pattern of use as: "continuer", "discontinuer" "switching" or "add-on". A Cox regression model was used to analyse the factors influencing therapy discontinuation. Primary-care costs comprised specialists' visits, diagnostic procedures and pharmacologic therapies. Results Among 14,999 subjects included in persistence analyses, 55.1% of cases initially started on monotherapy were classified as discontinuers vs 36.5% of cases taking combination therapy (42.3% vs 32.7%, respectively, for free and fixed combinations, P < 0.01). Old age, high cardiovascular risk and being in receipt of fixed-combination therapy were associated with greater persistence. Overall, the primary-care cost/person/year of hypertension management was ~€95.3 (IQR, 144.9). The monotherapy cost was €88 per patient (IQR, 132.9), and that for combination therapy was €151±148.3. The median cost/patient with a fixed combination was lower than that for a free combination (€98.4 (IQR, 155.3) and €154.9 (IQR, 182.6), respectively). Conclusion The initial type of therapy prescribed influences persistence. Prescribing fixed combinations might be a good choice as initial therapy.

Lysozyme is particularly attractive for the local treatment of oral pathologies related to microbiological infections. However, the requirement of a prolonged release is difficult to achieve because of saliva swallowing and of the protein denaturation which can occur during production and storage of a dosage form. This work demonstrates the feasibility to prepare lysozyme mucoadhesive tablets by freeze-drying. Tablets were prepared by using alginate (ALG) physically “cross-linked” with calcium ion and different grades of hydroxypropyl methylcellulose (HPMC) (i.e., E5, E50, or K100). The tablets were characterized in terms of swelling or erosion behavior, in vitro mucoadhesive properties, lysozyme activity (Micrococcus lysodeikticus), drug release and ability to inactivate Staphylococcus aureus. The formulations prepared with HPMC K100 were discarded because of the fast erosion. All other formulations allowed a sustained release over at least 6 h. Independently of composition, lysozyme activity (78,311 ± 1873 Units/mg) significantly decreased in the case of tablets containing 5% and 10% w/w of protein (55,000 Units/mg and 33,000 Units/mg, respectively). Conversely, no modifications occurred in the case of tablets containing 1% w/w lysozyme. The formulation prepared by ALG/HPMC E5 7/3 ratio was efficacious against S. aureus. After 3 months of storage at 5 ± 3°C, no significant decrease in lysozyme activity was observed.

Tattoo prevalence has been increasing in the last 25 years, but specific regulations on tattoo inks are still missing. In the European Union, no supranational regulation is available and only few national provisions cover them. In the United States, tattoo inks are classified as cosmetics but are not approved for injection into the dermis. Health risks for consumers may derive from microbiological contamination and the presence of toxic substances or nanomaterials. However, current regulations and non-binding recommendations, where present, only address the microbiological and chemical risks, completely overlooking nanotoxicity. The aim of this paper is to promote awareness of the risks associated with tattoo inks and the nanomaterials contained therein. In particular, the need for a harmonised regulation or, at least, a set of minimal requirements is highlighted to improve the safety of tattoo inks and market surveillance by regulatory authorities.

The experience gained with biosimilars has made it clear that copies of complex drugs are more challenging to produce and put on the market than generics. In the case of so-called nonbiological complex drugs (NBCDs), the complexity can arise either from a complex active substance or by other factors, such as formulation or route of delivery. Regulatory policies in the USA and the EU for the marketing of NBCD copies are reviewed, using glatiramer acetate copies as a case study. In the USA, they are approved and marketed as generics (although needing additional data), and so they are interchangeable with the originator. In the EU, they are managed with a hybrid application, and their interchangeability and substitution are established by individual member states.

Graphical abstract, Medicine shortages have been spreading in European countries. In many cases, the unavailability of medicinal products has a substantial impact on the capability of National Healthcare Systems in ensuring the continuity of care. Shortages originate from multifactorial causes. In particular, they can be due to supply-related factors (e.g., manufacturing issues, regulatory issues, logistics, distribution) and demand-related ones (e.g., fluctuating drug demand, parallel market, tendering, price and reimbursement policies). However, some extraordinary geopolitical events (e.g., Brexit) may also affect medicines’ availability. The capability of European Regulatory Authorities and other stakeholders, which are involved in the pharmaceutical distribution chain and the healthcare assistance services, to define suitable problem-solving strategies has been limited for years by the fragmentation of the European regulatory framework, starting from the lack of a univocal definition of a medicine shortage. Only in 2019, the EMA and HMA joint task force released the first harmonized “shortage” definition in the European Economic Area (EEA) and guidance on public communication. This manuscript aims to review the current European regulatory framework on medicine shortages. To support the activities of regulators, manufacturers and other healthcare professionals, an algorithm was also proposed to be used as a harmonized procedure to determine the shortage/unavailability impact on public health and to rationalize the problem-solving strategies adopted in all different settings.

Transdermal patches and medicated plasters are designed to sustain efficacious systemic or loco-regional drug concentrations, respectively. In both cases, drug skin permeation is a critical attribute from the early stage of the pharmaceutical development. In 2014, the EMA introduced the "Guideline on the quality of transdermal patches", in which the importance of equivalence of drug fluxes in in vitro skin permeation study was particularly emphasized to generic or abridged applications for the marketing authorization or manage dossier variations during the product cycle life. Moving from experimental data, this work provides information on the set-up of such studies and the statistical evaluation of obtained fluxes. In particular, the impact of the inter-sample variability on the equivalence assessment was deeply investigated by using formulation pairs containing propranolol, diclofenac or nitroglycerine. The main outputs of the work were attributable to the definition of the acceptability interval and number of replicates to be performed. As an example, the equivalence of two propranolol patches (flux variability lower than 25%) can be assessed using six replicas and a confidence limit within the 0.8–1.25 range (α = 0.05; power 90%). In contrast, the equivalence of diclofenac plasters, which exhibit a variability near the 50%, can be demonstrated increasing the number of replicas (i.e., 20 skin samples) for each formulation and widening the acceptance range according to the statistical approach proposed in the work.

Orodispersible dosage forms have a growing presence in the pharmaceutical market because their administration can improve the bioavailability of some drugs and their prescription can ameliorate patient adherence and/or compliance. Here, we review the main features of orodispersible tablets, including oral lyophilisates, and orodispersible films along with their main production technologies. We summarize the bioavailability data and critically discussed their potential to improve patient adherence and/or compliance. We revisit this information in light of both the European Union (EU) and US regulatory frameworks, focusing on the differences in the definitions of such dosage forms and the requirements for marketing authorization.

The work aimed to evaluate the feasibility to design hyaluronic acid (HA) decorated flexible liposomes to enhance the skin penetration of nifedipine. Egg phosphatidylcholine (e-PC) based transfersomes (Tween 80) and transethosomes (ethanol) were prepared. HA was reacted with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (HA-DPPE) and two molar ratios (0.5 and 3%) of conjugate with respect to e-PC were tested. The presence of HA significantly increased the packing order of the bilayer (as verified by differential scanning calorimetry), reducing both the encapsulation efficiency and the flexibility of the decorated liposomes in a dose-dependent manner. In fact, at the highest HA content the constant of deformability (K, N/mm) increased and the carriers remained on the skin surface after topical application. The stiffening effect of HA was counterbalanced by the addition of ethanol as fluidizing agent that allowed to maintain the highest HA concentration, meanwhile reducing the K value of the vesicles. HA-transethosomes allowed a suitable nifedipine permeation (J ∼ 30 ng/cm2/h) and significantly improved the drug penetration, favouring the formation of a drug depot in the epidermis. These data suggest the potentialities of HA-transethosomes as drug delivery systems intended for the treatment of cutaneous pathologies and underline the importance of studying the effect of surface functionalization on carrier deformability to rationalize the design of such systems.

Barrier creams (BC) are marketed as cosmetic products or locally-applied medical devices to protect skin against damages induced by chemical agents or physical insults. However, the determination of the BC effectiveness is still a matter of discussion at both the clinical and the regulatory level. In this context, this work aimed at the development of a reliable, reproducible and easy-to-perform experimental protocol for the evaluation of BC performances. Preliminarily, an in vivo method based on the measurement of trans-epidermal water loss had been matter of investigation and was discarded: it required too much time and was not robust and sensitive enough. In vitro, reduction of the permeation of caffeine (used as a model of irritant), through an epidermal membrane mounted on a Franz cell or through a reconstructed 3D human epidermis model, was evaluated. Six BC among oil in water (O/W) or water in oil (W/O) creams were investigated with respect to the petrolatum, which is an efficient impermeable barrier against hydrophilic molecules. Despite minor differences, both methods could rate the effectiveness of the tested products in preventing caffeine exposure. Both methods enable to evaluate and quantify the BC effectiveness in a simple and fast manner. Their application may help regulatory agencies to prevent the marketing of ineffective products for the benefit of consumers.

Purpose To analyse the pattern of use and cost of antihypertensive drugs in new users in an Italian population, and explore the patient/treatment factors associated with the risk of therapy discontinuation. Patients and methods In this retrospective study, information was collected from a population-based electronic primary-care database. Persistence with medication use 1 year from therapy initiation was evaluated for each user using the gap method. Each new user was classified according to his/her pattern of use as: “continuer”, “discontinuer” “switching” or “add-on”. A Cox regression model was used to analyse the factors influencing therapy discontinuation. Primary-care costs comprised specialists’ visits, diagnostic procedures and pharmacologic therapies. Results Among 14,999 subjects included in persistence analyses, 55.1% of cases initially started on monotherapy were classified as discontinuers vs 36.5% of cases taking combination therapy (42.3% vs 32.7%, respectively, for free and fixed combinations, P < 0.01). Old age, high cardiovascular risk and being in receipt of fixed-combination therapy were associated with greater persistence. Overall, the primary-care cost/person/year of hypertension management was ~€95.3 (IQR, 144.9). The monotherapy cost was €88 per patient (IQR, 132.9), and that for combination therapy was €151±148.3. The median cost/patient with a fixed combination was lower than that for a free combination (€98.4 (IQR, 155.3) and €154.9 (IQR, 182.6), respectively). Conclusion The initial type of therapy prescribed influences persistence. Prescribing fixed combinations might be a good choice as initial therapy.

Umberto Maria Musazzi,1 Paolo Rocco,1 Cinzia Brunelli,2,3 Luisa Bisaglia,4 Augusto Caraceni,2,3 Paola Minghetti1 1Department of Pharmaceutical Sciences, University of Milan, Milan, Italy; 2Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy; 3European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 4Department of Statistical Sciences, University of Padua, Padua, Italy Purpose: In Italy, where the adoption of opioid analgesics in pain management has been historically poor, an increase in opioids consumption occurred between 2000 and 2015. The aim of this study is to assess, through specific time series analyses for trend changes, the impact of different intervening factors – such as the availability of new drugs, the observance of clinical guidelines, changes in prescription regulations, and in reimbursement policies – on opioids sales to community pharmacies in Italy, focusing on the time period 2000–2010. Materials and methods: Five opioids were considered: codeine, tramadol, buprenorphine, morphine, and fentanyl. The analysis is based on sales data collected at wholesale distributors. For each one of the five drugs, time series of the number of Defined Daily Doses per thousand inhabitants per day in the period 2000–2010 were analyzed, and an estimation of breakpoints was performed using segmented linear regression. Results: Drug sales underwent a sharp increase in 2000–2010, although on different scales. Segmented regression analysis highlighted different potential breakpoints, corresponding to either a significant change in value and/or in slope. Sales of the five opioids were affected by at least one relevant event, often due to a synergy of regulatory, marketing, and technological factors. The effect of reimbursement changes has proved important. Conclusion: Between 2000 and 2010, regulatory, technological, and reimbursement changes significantly influenced opioid sales to community pharmacies in Italy. The sales of relatively new drug products seem to be less influenced by changes in reimbursement and regulatory policies than that of more established products, suggesting that physicians are more comfortable with “old” drugs, since their clinical use is supported by established clinical guidelines and protocols. Keywords: opioids sales, community pharmacy, reimbursement policy, legislation changes, breakpoint estimation

Background/Aim: Topical β-blockers have recently been proposed as a valid alternative to oral drugs for treating cutaneous infantile haemangiomas, but clinical results in the literature are inconsistent due to the empirical choice of topical preparations. The current investigation aimed to rationalize the selection of a semi-solid vehicle for a locally applied drug product containing 1% w/w propranolol hydrochloride (PR-Cl). Methods: A hydrophobic ointment of PR-Cl, two lipophilic creams, and a hydrophilic cream were prepared. In vitro release and skin permeation studies through human epidermis and full-thickness skin were performed by Franz diffusion cells. Results: The overall results highlighted that PR-Cl was able to permeate the human epidermis, and its penetration pattern was strongly influenced by the composition of the semi-solid vehicle. PR-Cl release and permeation from lipophilic vehicles were extremely limited and influenced by their composition. Best results were obtained by using the hydrophilic cream. Furthermore, the retention study evidenced that epidermis acted as a reservoir, releasing the PR-Cl accumulated after preparation removal. Conclusion: The 1% w/w PR-Cl cream resulted the most suitable formulation for improving drug permeation through the human epidermis. On the contrary, the negligible permeation profile through full-thickness skin pointed out that PR-Cl cannot diffuse significantly to reach the deeper layers of human skin.

One of the most critical quality attributes of orodispersible films (ODFs) is related to the development of dosage forms with tensile properties suitable for the packaging and patient's handling. Aiming to develop a strategy to reinforce the tensile properties, the current work reported the feasibility to improve the tensile strength of maltodextrins (MDX) based ODFs by adding an amorphous water insoluble nanofiller, namely polyvinylacetate (PVAc). The possible interactions between components investigated by DSC and ATR-FTIR spectroscopy revealed that MDX and PVAc were immiscible; even if, the presence of plasticizers permitted the homogeneous dispersion of PVAc in the film until the 10% w/w concentration was reached. As a consequence, PVAc nanoparticles was found to be an effective reinforcing agent only at the concentrations of 3 and 5% w/w. In this optimal range, the tensile strength increased at least 1.5 fold and the elastic modulus increased at least 4 times.

Supersaturated systems have attracted interest to enhance the skin penetration because of the low cost and reduced risks of irritation with respect to other approaches. The mechanism is simply based on the increased drug driving force for transit out of the dosage form and penetrate the stratum corneum. Supersaturated systems can be obtained by preparation of solvent/non-solvent mixtures; or mixtures containing a skin penetrating solvent or a volatile solvent, and quenching. All methods are described to obtain solutions or semisolid preparations; meanwhile the solvent evaporation and quenching can be used in the transdermal patch production. The adopted formulative strategies can increase the drug concentration in the vehicle 5-fold the solubility and the corresponding increment of the thermodynamic activity determines a significant increase of the drug flux through the skin, according to the Fick's law. The main limitation of supersaturated systems is related to their thermodynamic instability that, leading to drug crystallization in the vehicle, affects the drug skin penetration. Among the possible strategies to avoid or retard this issue the use of polymeric materials appears the most efficacious. However, the crystallization of a drug during storage and/or application on the skin is driven by so many factors that the stability of supersaturated systems is unpredictable. This paper offers a comprehensive review of the literature with the aim to underline the "pros and cons" of the application of supersaturation in transdermal delivery in the light of the theoretical aspects.

Objectives Community pharmacists are the most accessible healthcare professionals. They interact with a large number of patients who often show emotional concern. Their stressful and complex role is widely acknowledged, nonetheless research on their personal life is practically non-existent. Thus, we set out to qualitatively explore the emotional perceptions of pharmacists. Methods Twenty experienced pharmacists were interviewed by a psychologist and a pharmacist. Data were analysed using an interpretative phenomenological analysis and coded using NVivo qualitative data analysis software. Key findings Interviewed pharmacists admitted to different types of difficulties, mostly arising from a series of small, standalone episodes. Their stories describe intrinsic difficulties with their practice, rather than personal experiences. This study reveals the complexity of a community pharmacists' role – divided into health and hygiene advice, counselling and empathic relationships, and entrepreneurship. An important obstacle is the integration and concomitant implementation of these components. Endogenous factors such as personal experiences, personality and academic background, and exogenous factors such as social status of the patient population, legal and administrative issues and location, all affect pharmacists' ability to cope with their role. Conclusions Improving health care can be obtained by incorporating community pharmacists into the healthcare team. Technical training is important in order to improve relationship skills and personal coping strategies. Further studies are recommended to provide a simple tool for measuring aspects of the personal and emotional aspects (inner life) of a community pharmacist.

The protection rights of low molecular weight heparins (LMWHs) are expired or are expiring, so the extent and nature of the studies required to obtain a market authorization for LMWH copies represents a hot topic. FDA classifies LMWHs as semisynthetic drugs and their copies as generics whereas the EMA views them as biological medicines and consequently their copies as biosimilars. Consequently, FDA requires only in vivo pharmacodynamic studies, while EMA requires also clinical trials. The current work reviews the chemical composition and therapeutic indications of LMWHs available in the EU and USA markets to discuss the two different approaches. Because LMWHs show a high intrinsic variability and a complete characterization is not viable, a conservative approach is desirable.

A study on urinary metabolites of methylprednisolone acetate (MPA) has been performed by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) in precursor ion scanning (PIS) and neutral loss (NL) modes. Patients suffering from joint inflammation have been treated with Depo-Medrol® (MPA marketed suspension, 40 mg) intra-articularly (IA) and after a wash-out period, intramuscularly (IM) at the same dose. Urine samples have been collected after both the administration routes. Metabolites were identified in PIS mode by setting the fragment ion at m/z 161 which is specific for MPA, methylprednisolone (MP), methylprednisolone hemisuccinate, and in NL mode by selecting the losses of 54, 72, 176 and 194 Da. The MP-related structure of each target ion detected in both the MS modes was then confirmed by MS/MS acquisitions, and by accurate mass experiments. By using this approach, 13 MPA metabolites (M1-M13) have been identified, nine already reported in the literature and four unknown and for which the chemical structures have been proposed. No differences in the metabolic pattern of MPA when administered IM or IA were observed. The relative abundances of metabolites compared with the internal standard (MP-D2) were monitored by multiple reaction monitoring analysis for 19 days after both the administration routes.

The work aimed at studying a new mucoadhesive prolonged release tablet containing 24μg clobetasol-17 propionate (CP) suitable for the management of oral lichen planus. Low swellable dosage forms were designed by combining a mucoadhesive polymer, i.e. poly(sodium methacrylate, methylmethacrylate), with hydroxypropylmethylcellulose and MgCl2. This formulation was selected to modify the tablet erosion rate in order to obtain a release of CP over a 6-h period. A double-blind, controlled study was performed using three groups of patient (n=16) who received three applications-a-day over 4weeks of the developed CP tablets (group CP-T), placebo tablets (group CP-P) or commercial CP ointment for cutaneous application (123μg/application) extemporary mixed with Orabase™ (group CP-O). At the end of the study, pain and ulceration resolved in 13/16 and 11/16 patients of group CP-T and group CP-O, respectively. In the group CP-O, a transient acute hyperaemic candidosis (n=2) and taste alteration (n=4) were also observed. No changes in clinical signs of patients in the group CP-P were evident. The application of mucoadhesive tablet containing 24μg CP 3 times a day appeared to be effective, avoiding the side effects of the generally used treatment. © 2010 Elsevier B.V. The work aimed at studying a new mucoadhesive prolonged release tablet containing 24μg clobetasol-17 propionate (CP) suitable for the management of oral lichen planus. Low swellable dosage forms were designed by combining a mucoadhesive polymer, i.e. poly(sodium methacrylate, methylmethacrylate), with hydroxypropylmethylcellulose and MgCl2. This formulation was selected to modify the tablet erosion rate in order to obtain a release of CP over a 6-h period. A double-blind, controlled study was performed using three groups of patient (n=16) who received three applications-a-day over 4weeks of the developed CP tablets (group CP-T), placebo tablets (group CP-P) or commercial CP ointment for cutaneous application (123μg/application) extemporary mixed with Orabase™ (group CP-O). At the end of the study, pain and ulceration resolved in 13/16 and 11/16 patients of group CP-T and group CP-O, respectively. In the group CP-O, a transient acute hyperaemic candidosis (n=2) and taste alteration (n=4) were also observed. No changes in clinical signs of patients in the group CP-P were evident. The application of mucoadhesive tablet containing 24μg CP 3 times a day appeared to be effective, avoiding the side effects of the generally used treatment. © 2010 Elsevier B.V.

Objectives Authorized medicinal products placed on the market do not cover all therapeutic needs. In order to meet the patient's legitimate right, a physician can prescribe other pharmacological treatments in other ways: off-label prescriptions, compounded medicinal products, compassionate use of medicinal products and medicinal products authorized in foreign countries. This is a critical review of the actual regulations which govern these alternatives, with particular attention to the Italian situation. Key findings and summary The legality of prescribing and dispensing approved drugs or devices for uses not included in their official labelling is sometimes a cause for concern and confusion. The public administration should always safeguard patients' rights and health, evaluating the appropriateness of medical prescriptions. Off-label use should be based on sound scientific evidence, expert medical judgement and published literature. In its attempt to avoid misuse, the public administration should not limit prescribing activity by issuing rigid the rules to be followed. The physician and the pharmacist have to be trained to assess the risks associated with a single therapy and/or absence of therapy to evaluate the best practice case by case.

Objective: Media are a main source of medical information for the public, as well as for decision makers. This scenario demands a good selection of stories and correct medical reporting. Design: Our study aimed to analyze if journalistic guidelines or similar documents were already available and whether they provided satisfactory advice for appropriate communication in the field, and to detail recommendations which could become a reference working document. Methodology: Sources for this paper were obtained from PubMed and from websites (and related links) of organizations known to be working in the area of health reporting. Documents providing recommendations for the activity were analyzed and compared through a scheme including nine macro-categories relevant to the selection, verification and building of the story, considering scientific and journalistic issues. The scheme was derived from the most complete document.We then compiled a comprehensive list of recommendations merging the contents of the documents considered and our professional experience. Results: Nine existing guidelines and similar documents representing the worldwide situation were compared. All the documents examined provided interesting indications. Some of these indications shared the basic principles of mainstream journalism (reliability and independence of sources); others were more specific, such as the understanding of the scientific method and its jargon, the need to avoid extrapolations and to understand the difference between in vitro and animal studies and clinical trials, statistical parameters, and so on. Most of the topics specific for health communication are concepts which can be grasped only with an adequate scientific background and continuing education.The nature and level of the details provided by these documents vary considerably and in most cases can be fully understood only by experienced journalists with a relevant background. Discussion: Our proposal provides a useful tool listing nearly 70 recommendations ranging from the education of journalists, to all the aspects of selection, understanding and translating of medical and drug information deriving from scientific reports. It is intended for a journalist with a biomedical background, and therefore highlights critical issues without providing detailed descriptions. The proposal endeavors to answer to the main criticisms of medical journalism, particularly the use of sources, the verification of clinical value, the need to follow up on the story. Our work focuses on the prerequisite for a medical journalist to acquire the knowledge that enables him to assess the results of pharmacological and medical research in order to accurately and reliably convey his message to a lay reader. The strength of our working paper derives from the preliminary ‘benchmarking’ of existing documents, as suggested in the literature, but even more so from the concerted effort of the authors, who represent the key stakeholders of the system (researchers, academic teachers, medical journalists and publishers). Conclusion: Our work identifies the major issues entailed in correct health reporting, and constitutes a step forward in overcoming existing barriers between scientists and journalists. The aim is to encourage the mediation of ‘public-centred’ information, which limits the false hopes and expectations that may arise due to communication problems between the two worlds.

The effects of two contra-ions, namely benzoate (Bz) and oleate (Ol), on the in vitro human skin permeability of propranolol racemate (RS-PR) or S-enantiomer (S-PR) were studied. Saline solution (SS) or mineral oil (MO) were selected as vehicles. The MO increased the permeability coefficient (K(p)) of PR-Bz (pK(p) approximately 4) of about four times with respect to SS (pK(p) approximately 8) probably due to the ion pair formation. The steady-state flux of S-enantiomers resulted about twofold higher than that of racemates according to their lower melting temperatures with the exception of (S)-PR-Ol and (RS)-PR-Ol vehicled in SS which not resulted statistically different. This anomalous result could be explained considering the behavior of (RS)-PR-Ol or (S)-PR-Ol in aqueous solutions: these salts formed ion pairs which associated to form aggregates up to a concentration of 20 microg/mL as verified by light scattering. Therefore, their effective concentrations in SS resulted similar and justified the overlapped skin permeation profiles. All three considered variables, namely counterion, vehicle, and chirality, resulted mutually interfering on and deeply influenced the passive diffusion process of PR.

This work aimed to evaluate the flexibility of a novel pyrolytic carbon coated drug-eluting stent platform, which presents the peculiarity of deep sculptures realized on the stent's outer surface (reservoirs). Tacrolimus (TCR) or TCR/excipient mixtures were loaded into the reservoirs, and their permanence into stent's reservoirs was verified by an in vitro short-time release test in human blood. Moreover, the impact of the excipients on the TCR physical state and surface morphology of the reservoirs and the release kinetics were studied. The reservoirs resulted homogeneously filled. Upon exposure to blood, no loss of materials from reservoirs was observed, and the drug release after 15 min was negligible in all cases. The loading procedure caused the drug amorphization and, AFM revealed that the surfaces were smooth and homogeneous with the exception of the TCR/poloxamer 188 mixture where spatial oriented crystals were evident. Poly(N-vinyl pyrrolidone) improved the in vitro TCR release rate constants (K). Poly(methylmethacrylate) (PMM) significantly reduced the K value both in vitro and in vivo. Indeed, the in vivo drug concentrations in rabbit artery wall significantly decreased, decreasing the TCR/PMM ratio. The characteristics of the stent strut resulted suitable to load material with different physicochemical characteristics.

Nitroflurbiprofen, NFP, a practically insoluble liquid drug, was microencapsulated in hydrophilic micromatrices made of poly(N-vinylpyrrolidone) (PVP), or polyaminomethacrylate (PAMA), or binary blends of polymers thereof. The PAMA/PVP miscibility was assessed both in the solid state (DSC and ATF-FTIR spectroscopy) and in solution by viscometric measurements. The in vitro NFP release test was carried out in over saturation condition to discriminate the increase of NFP apparent solubility (supersaturation degree, SD). Drug/polymer/polymer/water interactions were studied in silico by molecular dynamic (MD) simulations. PAMA and PVP resulted miscible only in aqueous solution. The release of NFP from microparticles occurred according to a non-monotonic pattern due to the formation of instable supersaturated systems and the drug separation in the dissolution medium. After 5 min, the SD was at least 3. The use of PVP/PAMA micromatrices reduced the instability of the supersaturated solutions. MD simulations evidenced that water molecules play a key role in the PAMA/PVP compatibilization process and in stabilization of NFP supersaturated systems by means of H-bond. The docking analyses here find a novel and successful application to predict the different ability of a drug to interact with polymeric blends in solution.

The present feasibility study was designed to obtain a monolayer patch containing oxybutynin (OXY) avoiding chemical permeation enhancers. The highest flux was obtained with a polydimethylsiloxane matrix patch. Because OXY crystals were detected in the matrix within a week, two amino methylmethacrylate copolymers (Eudragit E or Eudragit RS) were used as OXY crystallization inhibitors. A preliminary in vivo study indicated that flux from the stabilized patches had to be increased about 30-40%. This goal was reached by occlusion with a polyethylene layer.