In this study, we suggest optimizing the methodology to determine the Cohesion Index (Icd) in order to avoid mistaken characterizations due to powder bulk density. For this purpose, five different ...excipients, with different bulk densities and of different chemical nature, were compressed at different heights. Their compression and their tablet characterization enable establishing a powder weight for compression in accordance with its bulk density. Therefore, the resulting tablet will have a height within a defined range of heights where it has no critical effects on its hardness. Then, the impact of this optimization is shown in a formula development, one of the main SeDeM's applications. A mathematical equation was used to calculate the theoretical amount of excipient to formulate the API according to both methodologies. The compression results demonstrate that the characterization with the NM-Icd is more accurate than the previous one while preserving its simplicity.
Starting from late May 2012, the Emilia region (Northern Italy) was severely shaken by an intense seismic sequence, originated from a ML 5.9 earthquake on May 20th, at a hypocentral depth of 6.3km, ...with thrust-type focal mechanism. In the following days, the seismic rate remained high, counting 50 ML≥2.0 earthquakes a day, on average. Seismicity spreads along a 30km east–west elongated area, in the Po river alluvial plain, in the nearby of the cities Ferrara and Modena. Nine days after the first shock, another destructive thrust-type earthquake (ML 5.8) hit the area to the west, causing further damage and fatalities. Aftershocks following this second destructive event extended along the same east-westerly trend for further 20km to the west, thus illuminating an area of about 50km in length, on the whole. After the first shock struck, on May 20th, a dense network of temporary seismic stations, in addition to the permanent ones, was deployed in the meizoseismal area, leading to a sensible improvement of the earthquake monitoring capability there. A combined dataset, including three-component seismic waveforms recorded by both permanent and temporary stations, has been analyzed in order to obtain an appropriate 1-D velocity model for earthquake location in the study area. Here we describe the main seismological characteristics of this seismic sequence and, relying on refined earthquakes location, we make inferences on the geometry of the thrust system responsible for the two strongest shocks.
•First complete analysis of the 2012 Emilia mainshocks–aftershocks seismic sequence.•New catalog of the seismic sequence including data from temporary stations•Sensible improvement in terms of the activated fault system geometry definition•The different dip of the activated fault segments is highlighted and discussed.•Basic information are provided for further specific studies and hazard scenarios.
The Semi-solid Control Diagram (SSCD) is a new tool designed for the study of different excipients and different semi-solid dosage forms. It can be used to review and evaluate different formulations ...and/or batches and facilitate the selection of one of them that will present the most suitable galenic characteristics for topical application. It is also useful to track stability studies by comparing the diagrams, which allows to measure the impact of subjecting the formulation to different conditions and times to be examined. In this study, the Semi-solid Control Diagram (SSCD) is used as an instrument for studying and evaluating semi-solid pharmaceutical dosage forms, by comparing several different semisolid preparations (lipogels). With these results, the tool is validated and the best formulation has been discriminated from the others.
This theoretical study seeks to critically review the use of excipients in the paediatric population. This study is based on the rules and recommendations of European and American drug regulatory ...agencies. On the one hand, this review describes the most frequent excipients used in paediatric medicine formulations, identifying the compounds that scientific literature has marked as potentially harmful regarding the side effects generated after exposure. On the other hand, this review also highlights the importance of carrying out safety -checks on the excipients, which, in most cases, are linked to toxicity studies. An excipient in the compilation of paediatric population databases is expected to target safety and toxicity, as in the STEP database. Finally, a promising pharmaceutical form for child population, ODT (Orally Disintegrating Tablets), will be studied.
•Accurate 3D locations of the Emilia 2012 seismic sequence in Italy.•Geometry of thrust system buried beneath the Quaternary sediments of the Po Valley.•The different dip of the thrusts, steep or ...flat, led to the arc-like shape of the front.•Heterogeneity of the basement drives the structuration of the front.
The evolution of the Apennines thrust-and-fold belt is related to heterogeneous process of subduction and continental delamination that generates extension within the mountain range and compression on the outer front of the Adria lithosphere. While normal faulting earthquakes diffusely occur along the mountain chain, the sparse and poor seismicity in the compressional front does not permit to resolve the ambiguity that still exists about which structure accommodates the few mm/yr of convergence observed by geodetic data. In this study, we illustrate the 2012 Emilia seismic sequence that is the most significant series of moderate-to-large earthquakes developed during the past decades on the compressional front of the Apennines. Accurately located aftershocks, along with P-wave and Vp/Vs tomographic models, clearly reveal the geometry of the thrust system, buried beneath the Quaternary sediments of the Po Valley. The seismic sequence ruptured two distinct adjacent thrust faults, whose different dip, steep or flat, accounts for the development of the arc-like shape of the compressional front. The first shock of May 20 (Mw 6.0) developed on the middle Ferrara thrust that has a southward dip of about 30°. The second shock of May 29 (Mw 5.8) ruptured the Mirandola thrust that we define as a steep dipping (50–60°) pre-existing (Permo-Triassic) basement normal fault inverted during compression. The overall geometry of the fault system is controlled by heterogeneity of the basement inherited from the older extension. We also observe that the rupture directivity during the two main-shocks and the aftershocks concentration correlate with low Poisson ratio volumes, probably indicating that portions of the fault have experienced intense micro-damage.
In the years between 2011 and 2014, at the edge between the Apennines collapsing chain and the subducting Calabrian arc, intense seismic swarms occurred in the Pollino mountain belt. In this key ...region, <2.5 mm/yr of NE-trending extension is accommodated on an intricate network of normal faults, having almost the same direction as the mountain belt. The long-lasting seismic release consisted of different swarm episodes, where the strongest event coinciding with a
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5.0 shock occurred in October 2012. This latter comes after a
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four nucleated in May 2012 and followed by aseismic slip episodes. In this study, we present accurate relocations for ∼6,000 earthquakes and shear-wave splitting analysis for ∼22,600 event-station pairs. The seismicity distribution delineates two main clusters around the major shocks: in the north-western area, where the
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5.0 occurred, the hypocenters are localized in a ball-shaped volume of seismicity without defining any planar distribution, whilst in the eastern area, where the
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4.3 nucleates, the hypocenters define several faults of a complex system of thrusts and back-thrusts. This different behavior is also imaged by the anisotropic parameters results: a strong variability of fast directions is observed in the western sector, while stable orientations are visible in the eastern cluster. This tectonic system possibly formed as a positive flower structure but as of today, it accommodates stress on normal faults. The deep structure imaged by refined locations is overall consistent with the complex fault system recently mapped at the surface and with patterns of crustal anisotropy depicting fractures alignment at depth. The possible reactivation of inherited structures supports the important role of the Pollino fault as a composite wrench fault system along which, in the lower Pleistocene, the southward retreat of the ionian slab was accommodated; in this contest, the inversion of the faults kinematics indicates a probable southward shift of the slab edge. This interpretation may help to comprehend the physical mechanisms behind the seismic swarms of the region and defining the seismic hazard of the Pollino range: nowadays a region of high seismic hazard although no strong earthquakes are present in the historical record.
Prospectively planned designs of experiments (DoEs) offer a valuable approach to preventing collinearity issues that can result in statistical confusion, leading to misinterpretation and reducing the ...predictability of statistical models. However, it is also possible to develop models using historical data, provided that certain guidelines are followed to enhance and ensure proper statistical modeling. This article presents a methodology for constructing a design space using process data, while avoiding the common pitfalls associated with retrospective data analysis. For this study, data from a real wet granulation process were collected to pragmatically illustrate all the concepts and methods developed in this article.
Although some methods for measuring bioadhesion/mucoadhesion have been proposed, a standardized method is not yet available. This is expected to hinder systematic comparisons of results across ...studies. This study aimed to design a single/systematic in vitro method for measuring bioadhesion/mucoadhesion that is applicable to various pharmaceutical dosage forms. To this end, we measured the peak force and work of adhesion of minitablets, pellets, and a bioadhesive emulsion using a texture analyzer. Porcine tissue was used to simulate human stomach/skin conditions. The results of these formulations were then compared to those for formulations without the bioadhesive product. We conducted a case study to assess the stability of a bioadhesive emulsion. The results for the two parameters assessed were contact time = 60 s and contact force = 0.5 N at a detachment speed of 0.1 mm/s. Significant differences were observed between the bioadhesive and control formulations, thus demonstrating the adhesive capacity of the bioadhesive formulations. In this way, a systematic method for assessing the bioadhesive capacity of pharmaceutical dosage forms was developed. The method proposed here may enable comparisons of results across studies, i.e., results obtained using the same and different pharmaceutical formulations (in terms of their bioadhesion/mucoadhesion capacity). This method may also facilitate the selection of potentially suitable formulations and adhesive products (in terms of bioadhesive properties).
Carvedilol (CARV) is an ‘off-label’ β-blocker drug to treat cardiovascular diseases in children. Since CARV is nearly insoluble in water, only CARV solid forms are commercialized. Usually, CARV ...tablets are manipulated to prepare an extemporaneous liquid formulation for children in hospitals. We studied CARV to improve its aqueous solubility and develop an oral solution. In this study, we assessed the solubility and preliminary stability of CARV in different pH media. Using malic acid as a solubility enhancer had satisfactory results. We studied the chemical, physical, and microbiological stability of 1 mg/mL CARV–malic acid solution. A design of experiment (DoE) was used to optimize the CARV solution’s preparation parameters. A 1 mg/mL CARV solution containing malic acid was stable for up to 12 months at 25 °C and 30 °C and 6 months at 40 °C. An equation associating malic acid with CARV concentrations was obtained using DoE. Microbiological data showed that the use of methylparaben was not necessary for this period of time. We successfully developed an aqueous CARV solution suitable for paediatrics and proven to be stable over a 12-month period.
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The production of 3D printed pharmaceuticals has thrived in recent years, as it allows the generation of customised medications in small batches. This is particularly helpful for ...patients who need specific doses or formulations, such as children. Compounding pharmacies seek alternatives to conventional solid oral doses, opting for oral liquid formulations. However, ensuring quality and stability, especially for pH-sensitive APIs like omeprazole, remains a challenge. This paper presents the application of semi-solid extrusion 3D printing technology to develop patient-tailored medicinal gummies, with an eye-catching appearances, serving as an innovative omeprazole pharmaceutical form for paediatric use. The study compares 3D printing hydrogels with dissolved omeprazole to hydrogels loaded with gastro-resistant omeprazole pellets, a ground-breaking approach.. Gastro-resistance and dissolution profiles were studied using different methods for better comparison and to emphasize the significance of the assay's methodology. Both developed formulas exhibit proper rheology, good printability, and meet content and mass uniformity standards. However, the high gastro-resistance and suitable release profile of 3D printed chewable semi-solid doses with enteric pellets highlight this as an effective strategy to address the challenge of paediatric medication.
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