Search

Résumé La notion de dispositif médical recouvre de multiples produits, de nombreuses technologies, des applications cliniques très diverses et implique en France des acteurs différents en nombre croissant disposant parfois d’un monopole. Les textes réglementaires français sont par conséquent souvent éparpillés tandis que le droit communautaire est encore en développement. Dans ce contexte complexe, le pharmacien français a toutefois un rôle pivot. Ce rôle est bien établi depuis 1992 pour la dispensation des dispositifs médicaux stériles à l’hôpital et a été plus généralement renforcé face au patient depuis 2002. En pratique, les pharmaciens sont donc confrontés à des situations diverses qui mettent en question le champ de leur exercice et leur responsabilité. En l’absence en France de « bonnes pratiques de dispensation » telles qu’il en existe pour les préparations ou les fabrications, cet article propose un état des lieux de la réglementation actuellement applicable concernant la dispensation des dispositifs médicaux et vise à apporter des réponses d’ordre réglementaire aux pharmaciens face à des situations atypiques ou de récents changements dans leurs pratiques professionnelles. The concept of medical device covers multiple products, multiple technologies, wide range of clinical applications and involves different actors in France in growing numbers sometimes with a monopoly. The French regulations are therefore often scattered while Community law is still developing. In this complex context, the French pharmacist however has a pivotal role. This role is well established since 1992 for the delivery of sterile medical devices in the hospital and was generally strengthened against the patient since 2002. In practice, pharmacists are faced with different situations that call into question the scope of their practice and responsibility. In the absence in France of “good dispensing practices” as they exist for preparations or fabrications, this article provides an overview of the current regulatory dispensation concerning medical devices. This review aims to provide answers to regulatory pharmacists facing atypical situations or recent changes in their professional practices. [ABSTRACT FROM AUTHOR]

Despite the development of new antifungal, amphotericin B remains one of the most effective agents in the treatment of systemic fungal infections. Many patients exhibit nevertheless intolerance to amphotericin B at higher dosages and parenteral formulations present unlike per os ones, associated risks and high care cost. Free amphotericin B per os showed however an apparently poor absorption. In this study, we evaluate the potential of amphotericin B liposomes formulated with vegetal ceramides for oral administration. Ceramides, one of the constituents of cellular cytoplasmic membranes, constitute an important element in the construction and stability of their lipid bilayer. To fulfill this objective, vegetal ceramides, composed essentially of glucosylceramides, were firstly incorporated in various liposome preparations, entrapping or not amphotericin B, in comparison with phosphatidylcholine liposomes. Then, these preparations were introduced in an “Artificial-Stomach–Duodenum” model to improve their stability for oral administration. The formulation of amphotericin B liposomes containing ceramides presented a mean hydrodynamic size of about 200 nm. We showed also that cholesterol and phospholipids are required to prevent drug leakage and to obtain lamellar structure respectively. In “Artificial-Stomach–Duodenum” model, ceramides conferred to liposomes better membrane stability. In addition, ceramides did not alter their drug encapsulation yield being by 75%. This could be explained by the fact that ceramides as we proved, limited the detergent effect of bile salts on liposome membranes. [ABSTRACT FROM AUTHOR]

In neonates as well as in adults having swallowing difficulty, oral medication is given through a nasogastric tube making liquid formulations preferable. In this study, we present the high potential of nanometric emulsions formulated by spontaneous surfactant diffusion, as extemporaneous formulations of hydrophobic drug. Spironolactone used as hydrophobic drug model, was incorporated in oil before formulation at a concentration of 13.5 mg/g oil. Then, all formulations were evaluated from pharmacotechnical and clinical standpoints, for their use in hospital or community pharmacy. The strength of this new liquid formulation lies on the simplicity, efficiency and reproducibility of their low energy process as on clinical aspects: high dose uniformity, facility to be administered through in nasogastric tube without any retention and a stability of 2 months at least compatible for an extemporaneous use. Moreover, this emulsion presented spironolactone content of 3.75 mg/ml among the most concentrated formulations published. [ABSTRACT FROM AUTHOR]

This pioneer study in the domain of blood pool contrast media formulation presents the influence of poly- ɛ-caprolactone-monomethoxy poly(ethylene glycol) (PCL-mPEG) and oils on the formulation of polymeric nanoparticles by emulsion-solvent diffusion. The nature of the oil used had no influence on the encapsulation rate, even if particles were formulated with a mix of PCL/PCL-mPEG. It did, however, influence the particle size and polydispersity, with macroglycerides appearing to be the lipid structure best suited to obtain the smallest monodisperse particles. When we used PCL-mPEG to form a PEG-hydrated layer to surround the nanoparticles, its tension active property had a favorable effect on particle size and polydispersity. We also showed the strong deleterious effect on particle size and polydispersity when the polymer proportion was increased to over 1% (w/v) in the pre-emulsion organic phase. Conversely, increasing the oil proportion in this organic phase simply resulted in a slight to insignificant deleterious effect on size and polydispersity, enabling the oil proportion to be enhanced up to 3% (w/v). Finally, we showed the favorable combined effect of oil iodination and the presence of PCL-mPEG on particles formulated by emulsion-solvent diffusion leading to the preparation of smaller polymeric iodine-containing particles. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4150-4158, 2013 [ABSTRACT FROM AUTHOR]

Purpose: Synthesis and formulation of iodinated PCL-mPEG nanocapsules as new original blood pool contrast agents for computed tomography. Methods: PCL-mPEG was synthesized and formulated following the emulsion-solvent diffusion process, in the form of iodinated nanocapsules. Physico-chemical characterization of such nano-materials was performed by DLS and transmission electron microscopy. A stability study of the nanocapsules suspension was followed-up to 3 month. Blood biocompatibility was performed. Finally, the nanocapsules suspension radiopacity was evaluated in vitro then in vivo in mice as micro-CT contrast agent. Results: In this study, the iodine concentration in nanocapsules suspension was about 70 mgI/mL. Besides, these nanocarriers appeared non-toxic, and stable in suspension. In vivo, i.v. administration of 10 μL/g of mouse body weight of theses nano-particles induced a vascular contrast enhancement of 168 HU and a half-life in blood of 4.2 +/− 0.5 h. Elimination route of these particles appears mainly performed by the liver, without sequestration in spleen and lymph nodes confirming their stealth properties. Conclusions: This study proposes the first example of iodinated biodegradable polymeric blood pool contrast agent, able to induce an exploitable contrast enhancement. The main advantage of polymeric system compared to lipid ones, lies in their stability and handling, e.g. towards drying for storage. [ABSTRACT FROM AUTHOR]

Abstract: This study presents new important aspects in the design of contrast agents for X-ray preclinical imaging. The first one is a new simple formulation of long circulating contrast agents, formulated from a commercial iodinated oil, and resulting in CT contrast agents containing more than twice the iodine concentration commercial contrast agents. The second point is a methodological aspect, utilizing tangential filtration for reducing the residual surfactants in the bulk phase and serving as well for concentrating droplets (and iodine) in the suspension. The last point is a more general aspect regarding the influence of the free surfactant on the pharmacokinetics and biodistribution of the nano-emulsion droplets on mice. We showed that cross-flow filtration is efficient for concentrating the droplets and reducing the concentration of free surfactant from 10wt.% to 1wt.%, without any changes in the nano-emulsion droplet morphologies or surface properties. We also showed that the presence of free surfactant has a significant impact on the elimination way of the nano-emulsion droplets, shared between liver and kidneys. The purified nano-emulsions are preferentially eliminated by the kidneys in contrast to raw nano-emulsions, predominantly eliminated by the liver. In practice, for two similar suspensions, half-life decreases from 4.1±1.10h to 2.5±0.77h before and after purification. Since the design and development of long circulating systems are critical in numerous domains, and not for preclinical CT imaging, this study presents important results in that field, taken under a formulation and technical point of view. [Copyright &y& Elsevier]

Abstract: Over the past decade, France has experienced two major reforms of its health system. Reform constitutes of the law of March the 4th 2002 has upset the relationship between health professionals and patients by introducing into the Public Health Code (CSP) a set of provisions on the right of patients and users of the health system (first legislative and regulatory part of the CSP). Reform of July, the 22nd 2009 at amending the relationships between different health professionals by encouraging them to work more through multiple channels (multidisciplinary meeting, personalized patient education…). Furthermore, this reform ended the division between the hospital, that of “city” and the medico-social environment. Consequently, drug regulation has been largely modified from the pivotal role of the pharmacist among health professionals. Nevertheless, the publication of Good Dispensing Practices (BPD) announced in the CSP are still not published. Thus waiting for the publication of these BPD, it seemed appropriate to produce a summary as complete as possible on the regulations related to pharmaceutical dispensing. [Copyright &y& Elsevier]

Abstract: The in vivo X-ray micro-computed tomography (micro-CT) is a very powerful and non-invasive tool used to establish high-resolution images with isotropic voxels in typical scan times ranging from minutes to tenths of minutes. This preclinical imaging technology is primarily adapted to visualize bones. X-ray imaging of soft tissues is made possible by using opaque compounds, providing contrast through tissue vascularization. Thus, using control agents with a long-lasting time in the blood, active or passive targeting of soft tissue is made possible in small animals. In this respect, the use of hydrophilic iodinated X-ray contrast media remains limited due to their rapid blood clearance, albeit at a slightly slower pace in humans as compared with rodents. The development of an iodinated contrast medium with increased vascular residence time is thus necessary. This is precisely the scope of the present paper, which will review and compare in detail the different vectors used as long-circulating iodinated contrast agents for micro-CT, i.e. liposomes, nano-emulsions, micelles, dendrimers and other polymeric particles. The discussion is focused, for each of these nanoparticulate systems, on their method of formulation and production, their stability properties, encapsulation properties, release properties, pharmacokinetics, and toxicology. The different aspects relative to the adaptation of these properties and physico-chemical characteristics for blood pool contrast agents aimed at angiographic micro-CT applications are also discussed. The aim of this review is to propose an overview into the formulation and properties of iodinated micro-CT contrast agents for preclinical applications. [Copyright &y& Elsevier]

Abstract: The pharmacist working in the dispensary, in PUI or in other dispensation structures, is exposed to several types of legal actions for negligence and/or damage. Like all others, the pharmacist is subject to common law allowing her to seek civil or criminal liability. Also as a member of an organized profession in professional, the pharmacist is also subject to an ethics designed to seek its moral responsibility to his peer''s pharmacists. For a decade, the pharmacist has acquired through its pivotal role between the different health professionals, new possibilities for action (therapeutic education, status of matching pharmacist, pharmacist referent status of residential homes for elderly dependents…). This leads to increasing research responsibility of the practitioner during actions in justices. Of the large number and scattered texts that regulate the service of dispensing pharmaceuticals, the pharmacist often has difficulty in understanding the scope and limits of its responsibilities in a dispensation. It therefore seemed appropriate to produce a summary as complete as possible civil liability, criminal and disciplinary related to the pharmacist dispensing the drug. [Copyright &y& Elsevier]

Purpose: The coronavirus disease 2019 (COVID-19) pandemic reshaped the usual risk: benefit equilibrium that became a trade-off between the infection exposure risk for the patient (and for staff) and the risk associated with delaying or cancelling the nuclear medicine examination. This study aimed at quantifying the impact of the first COVID-19 lockdown in France on nuclear medicine examination volume together with volume of examination cancellation and non-attendance. Methods: We retrospectively assessed the volume of planned examinations from 1 month before to 1 month after the first lockdown in French high-volume nuclear medicine departments (NMD) sharing the same information management system including both university hospitals, UH (n = 7), and cancer centres, CC (n = 2). Results: The study enrolled 31,628 consecutive patients referred for a nuclear medicine examination performed or not (NMEP or NMEnP). The total volume of NMEP significantly dropped by 43.4% between the 4 weeks before and after the starting of the lockdown. The comparison of the percentage of NMEP and NMEnP between UH and CC is significantly different (p < 0.001). The percentage of NMEP during the study was 67.9% in UH vs 84.7% in CC. Percentages of NMEnP in UH and CC were due respectively to cancellation by the patient (14.9 vs 7.4%), cancellation by the NMD (9.5 vs 3.4%), cancellation by the referring physician (5.1 vs 4.4%) and non-attender patients (2.7 vs 0.2%). Conclusion: The study underlines the public health issue caused by COVID-19 above the pandemic itself and should be useful in preparing for potential resource utilisation and staffing requirements. [ABSTRACT FROM AUTHOR]

Abstract: Inorganic nanomaterials based on heavy elements represent a new class of contrast agents for X-ray computed tomography (CT). Recent advances have shown that these materials are highly suited for CT imaging due to their high density and X-ray absorption capabilities. In this contribution, we demonstrated that tungsten oxide (WO3) nanoparticles coated by poly-ε-caprolactone (PCL) can be used as efficient contrast agent for CT imaging. The obtained particles were characterized by electron microscopy (TEM and SEM), and dynamic light scattering (DLS). We also validated their use for enhanced in vivo imaging, since these nanoparticles were observed to display high X-ray attenuation properties and circulation time (up to 3 h), permitting blood pool imaging. [Copyright &y& Elsevier]

Abstract: Micro-computed tomography (micro-CT) is an emerging imaging modality, due to the low cost of the imagers as well as their efficiency in establishing high-resolution (1–100 μm) three-dimensional images of small laboratory animals and facilitating rapid, structural and functional in vivo visualization. However use of a contrast agent is absolutely necessary when imaging soft tissues. The main limitation of micro-CT is the low efficiency and toxicity of the commercially available blood pool contrast agents. This study proposes new, efficient and non-toxic contrast agents for micro-CT imaging. This formulation consists of iodinated vitamin E (α-tocopheryl 2,3,5-triiodobenzoate) as an oily phase, formulated as liquid nano-emulsion droplets (by low-energy nano-emulsification), surrounded by a hairy PEG layer to confer stealth properties. The originality and strength of these new contrast agents lie not only in their outstanding contrasting properties, biocompatibility and low toxicity, but also in the simplicity of their fabrication: one-step synthesis of highly iodinated oil (iodine constitutes 41.7% of the oil molecule weight) and its spontaneous emulsification. After i.v. administration in mice (8.5% of blood volume), the product shows stealth properties towards the immune system and thus acts as an efficient blood pool contrast agent (t 1/2 = 9.0 h), exhibiting blood clearance following mono-exponential decay. A gradual accumulation predominantly due to hepatocyte uptake is observed and measured in the liver, establishing a strong hepatic contrast, persistent for more than four months. To summarize, in the current range of available or developed contrast agents for preclinical X-ray imaging, this agent appears to be one of the most efficient. [Copyright &y& Elsevier]

• Dosimetry for SIRT is becoming of paramount importance to achieve the best outcome. • Computer aided voxel-based dosimetry is different from conventional dosimetry. • Tumor overlap by SIRT and tumoral dosimetry are related to the overall survival. • Voxel-based dosimetry should be included in management of SIRT patients. Selective Internal Radiation Therapy (SIRT) is used for the treatment of hepatic tumors. The aim of this retrospective study was to compare two dosimetric approaches based on 99mTc-MAA SPECT/CT and 90Y PET/CT, using Simplicit90Y™ versus the supplier suggested method of activity calculation. A total of 19 patients underwent 21 SIRT after baseline angiography and 99mTc-MAA SPECT/CT, followed by 90Y PET/CT. Overlap between 99mTc-MAA and 90Y-microspheres was quantified with different thresholds isocontours. The perfused volume and tumor absorbed dose were estimated using Simplicit90Y™ based on SPECT/CT and PET/CT, then compared with the supplier suggested method. These data were related to overall survival to evaluate their prognostic impact. The overlap between PET/CT and SPECT/CT was dependent on thresholds, decreasing with an increasing threshold. The overlap between the 99mTc-MAA and 90Y-microspheres biodistributions versus the tumor distribution on morphological imaging was suboptimal, in particular for small tumor volume. The tumor absorbed dose estimated after 90Y PET/CT was not different from tumor absorbed dose estimated after SPECT/CT. The Perfused lobe absorbed dose was significantly lower while the volume of the perfused lobe was significantly higher when estimated by Simplicit90Y™ compared to the supplier suggested conventional approach. A statistical parameter based on overlap between tumor and 90Y-microspheres distribution as well as tumoral dosimetry was significantly related to the overall survival. Post-treatment imaging remains paramount to estimate the irradiation dosimetry, due to an imperfect overlap. The perfused volume could be estimated from functional imaging, given its impact on dosimetry. Finally, survival seems related to tumoral overlap and dosimetry. [ABSTRACT FROM AUTHOR]