63 research outputs found

    A consensus research agenda for optimising nasal drug delivery

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    Nasal drug delivery has specific challenges which are distinct from oral inhalation, alongside which it is often considered. The next generation of nasal products will be required to deliver new classes of molecule, e.g. vaccines, biologics and drugs with action in the brain or sinuses, to local and systemic therapeutic targets. Innovations and new tools/knowledge are required to design products to deliver these therapeutic agents to the right target at the right time in the right patients. We report the outcomes of an expert meeting convened to consider gaps in knowledge and unmet research needs in terms of (i) formulation and devices, (ii) meaningful product characterization and modeling, (iii) opportunities to modify absorption and clearance. Important research questions were identified in the areas of device and formulation innovation, critical quality attributes for different nasal products, development of nasal casts for drug deposition studies, improved experimental models, the use of simulations and nasal delivery in special populations. We offer these questions as a stimulus to research and suggest that they might be addressed most effectively by collaborative research endeavors

    CEDAR Electrodynamics Thermosphere Ionosphere (ETI) Challenge for systematic assessment of ionosphere/thermosphere models: Electron density, neutral density, NmF2, and hmF2 using space based observations

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    In an effort to quantitatively assess the current capabilities of Ionosphere/Thermosphere (IT) models, an IT model validation study using metrics was performed. This study is a main part of the CEDAR Electrodynamics Thermosphere Ionosphere (ETI) Challenge, which was initiated at the CEDAR workshop in 2009 to better comprehend strengths and weaknesses of models in predicting the IT system, and to trace improvements in ionospheric/thermospheric specification and forecast. For the challenge, two strong geomagnetic storms, four moderate storms, and three quiet time intervals were selected. For the selected events, we obtained four scores (i.e., RMS error, prediction efficiency, ratio of the maximum change in amplitudes, and ratio of the maximum amplitudes) to compare the performance of models in reproducing the selected physical parameters such as vertical drifts, electron and neutral densities, NmF2, and hmF2. In this paper, we present the results from comparing modeled values against space-based measurements including NmF2 and hmF2 from the CHAMP and COSMIC satellites, and electron and neutral densities at the CHAMP satellite locations. It is found that the accuracy of models varies with the metrics used, latitude and geomagnetic activity level

    CEDARâ GEM Challenge for Systematic Assessment of Ionosphere/Thermosphere Models in Predicting TEC During the 2006 December Storm Event

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    In order to assess current modeling capability of reproducing storm impacts on total electron content (TEC), we considered quantities such as TEC, TEC changes compared to quiet time values, and the maximum value of the TEC and TEC changes during a storm. We compared the quantities obtained from ionospheric models against groundâ based GPS TEC measurements during the 2006 AGU storm event (14â 15 December 2006) in the selected eight longitude sectors. We used 15 simulations obtained from eight ionospheric models, including empirical, physicsâ based, coupled ionosphereâ thermosphere, and data assimilation models. To quantitatively evaluate performance of the models in TEC prediction during the storm, we calculated skill scores such as RMS error, Normalized RMS error (NRMSE), ratio of the modeled to observed maximum increase (Yield), and the difference between the modeled peak time and observed peak time. Furthermore, to investigate latitudinal dependence of the performance of the models, the skill scores were calculated for five latitude regions. Our study shows that RMSE of TEC and TEC changes of the model simulations range from about 3 TECU (total electron content unit, 1 TECU = 1016 el mâ 2) (in high latitudes) to about 13 TECU (in low latitudes), which is larger than latitudinal average GPS TEC error of about 2 TECU. Most model simulations predict TEC better than TEC changes in terms of NRMSE and the difference in peak time, while the opposite holds true in terms of Yield. Model performance strongly depends on the quantities considered, the type of metrics used, and the latitude considered.Key PointsTEC and TEC changes during a storm predicted by ionosphere models were compared with groundâ based GPS TEC measurementsSkill scores (e.g., RMSE, NRMSE, and Yields) were calculated for five latitude regions in the selected eight longitude sectorsModel performance strongly depends on the quantities considered, the type of metrics used, and the latitude consideredPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139943/1/swe20516.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139943/2/swe20516_am.pd

    Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.

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    Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend <sup>®</sup> excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies

    Quantitative estimates of relationships between geomagnetic activity and equatorial spread-F as determined by TID occurrence levels

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    Using a world-wide set of stations for 15 years, quantitative estimates of changes to equatorial spread-F (ESF) occurrence rates obtained from ionogram scalings, have been determined for a range of geomagnetic activity (GA) levels, as well as for four different levels of solar activity. Average occurrence rates were used as a reference. The percentage changes vary significantly depending on these subdivisions. For example for very high GA the inverse association is recorded by a change of -33% for R-z greater than or equal to 150, and -10% for R-z < 50. Using data for 9 years for the equatorial station, Huancayo, these measurements of ESF which indicate the presence of TIDs, have also been investigated by somewhat similar analyses. Additional parameters were used which involved the local times of GA, with the ESF being examined separately for occurrence pre-midnight (PM) and after-midnight (AM). Again the negative changes were most pronounced for high GA in R-z-max years (-21%). This result is for PM ESF for GA at a local time of 1700. There were increased ESF levels (+31%) for AM ESF in R-z-min years for high GA around 2300 LT. This additional knowledge of the influence of GA on ESF occurrence involving not only percentage changes, but these values for a range of parameter levels, may be useful if ever short-term forecasts are needed. There is some discussion on comparisons which can be made between ESF results obtained by coherent scatter from incoherent-scatter equipment and those obtained by ionosondes
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