Printfills: 3D printed systems combining fused deposition modeling and injection volume filling. Application to colon-specific drug delivery

Three-dimensional printing has become a feasible manufacturing technique for pharmaceutical products providing cheap and accurate freeform systems with a great potential for personalized-dose drugs. Fused Deposition Modeling (FDM) highlights among other 3D technologies due to its low cost and easy to operate but, until now, it has the drawbacks of the low drug loaded and the impossibility to print thermosensitive drugs. So, intermediate processes such as hot melt extrusion are frequently associated with FDM. Here, pharmaceutical dosage forms have been manufactured for the first time with a 3D printer combining two different printing technologies: FDM and injection volume filling (IVF), performing customized extruded scaffolds in which a liquid or semisolid system can be injected at room temperature. A model drug and a pH-sensitive polymer were successfully incorporated during the construction of the extruded backbone of the systems, called printfills (printed systems filled with a liquid or semisolid). SEM microphotographs of printfills show the sealing of the structure in the perimeter and the homogeneity of the colonic film formed in the upper side. Thus, the addition of the pH-sensitive polymer does not need an additional process in a fluidized bed or coating pan. Results from drug release studies performed at different pH confirm the ability of printfills for colon-specific drug delivery. Therefore, IVF technology complements FDM, solving its main limitations providing an easy, automatized and versatile technology to manufacture tailored drug delivery platforms, avoiding other intermediate processes.Ministerio de Economía y Competitividad (MAT2016-77345-C3-3-P

Critical points for predicting 3D printable filaments behaviour

Fractal dimension has been employed for the first time to provide key information about the behaviour of extruded filaments. High drug loaded filaments made of thermoplastic polyurethane and anhydrous theophylline (10–70% w/w of drug content) have been obtained by using a single screw extruder. Fractal analysis was carried out based on the measures of the perimeter of the filaments at different magnification levels, using the box-counting technique approach. The fractal dimension values showed a critical point at 37.8% w/w of drug, which agrees with the behaviour of the printability of the filaments by FDM. The drug percolation threshold derived from drug release results was also in agreement with this critical point. Thus, both approaches concur in the estimation of a critical point around 38% w/w of drug, where printability and dissolution behaviour dramatically change. Therefore, the Fractal Dimension analysis could be considered as a non-destructive, non-expensive and fast method for estimating a crucial parameter for FDM 3D printing as is printability of the filament.MCIN/AEI RTI2018-095041-B-C3

Assessment of the Extrusion Process and Printability of Suspension-Type Drug-Loaded AffinisolTM Filaments for 3D Printing

Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim of this work was to evaluate the extrusion process and the physical appearance of filaments made of a hydrophilic polymer and a non-molten model drug. Metformin was used as model drug and Affinisol™ 15LV as the main carrier. Drug-loaded filaments were obtained by using a single-screw extruder and, subsequently, their printability was tested. Blends containing up to a 60% and 50% drug load with 5% and 7.5% of auxiliary excipients, respectively, were successfully extruded. Between the obtained filaments, those containing up to 50% of the drug were suitable for use in FDM 3D printing. The studied parameters, including residence time, flow speed, brittleness, and fractal dimension, reflect a critical point in the extrusion process at between 30–40% drug load. This finding could be essential for understanding the behaviour of filaments containing a non-molten component

3D printed drug delivery systems based on natural products

In the last few years, the employment of 3D printing technologies in the manufacture of drug delivery systems has increased, due to the advantages that they offer for personalized medicine. Thus, the possibility of producing sophisticated and tailor-made structures loaded with drugs intended for tissue engineering and optimizing the drug dose is particularly interesting in the case of pediatric and geriatric population. Natural products provide a wide range of advantages for their application as pharmaceutical excipients, as well as in scaffolds purposed for tissue engineering prepared by 3D printing technologies. The ability of biopolymers to form hydrogels is exploited in pressure assisted microsyringe and inkjet techniques, resulting in suitable porous matrices for the printing of living cells, as well as thermolabile drugs. In this review, we analyze the 3D printing technologies employed for the preparation of drug delivery systems based on natural products. Moreover, the 3D printed drug delivery systems containing natural products are described, highlighting the advantages offered by these types of excipients.Ministerio de Ciencia, Innovación y Universidades RTI2018-095041-B-C3

Impact of moderate coronary atherosclerosis on long-term left ventricular remodeling after aortic valve replacement

Background: The role of coronary atherosclerosis (CA+) in ventricular remodeling after aortic valve replacement (AVR) for isolated aortic stenosis (AS) is not well defined. We sought to evaluate the impact of not revascularized moderate coronary atherosclerosis in long-term left ventricular (LV) remodeling after AVR. Methods: We assessed by coronariography the coronary artery disease in 66 patients referred for AVR and evaluated morphological and functional LV data by echocardiography both preoperatively and postoperatively (3 ± 1.2 years). Results: In patients without coronary atherosclerosis, hypertrophy regression was more intense and the absolute reverse remodeling was higher in LV mass index (–55.8 ± 36 g/m2 vs –28.4 ± 34 g/m2, p = 0.004), reduction of LV dimensions (LV end-diastolic diameter [LVEDD]: –4.1 ± 7.4 mm vs –2.2 ± 8.3 mm, p = 0.04), and regression of wall thickness (interventricular septum [IVS]: –3.3 ± 2.6 mm vs –1.6 ± 2.2 mm, p = 0.01; and posterior wall thickness [PWT]: –2.1 ± 2.1 mm vs 0.6 ± 2.1 mm, p = 0.012). Conclusions: After AVR for AS, not revascularized moderate coronary atherosclerosis determines a long-term lesser degree of LV hypertrophy regression and a worse absolute reverse remodeling of LV mass index, LVEDD, IVS and PWT. (Cardiol J 2011; 18, 3: 277–281

Image matching algorithms in stereo vision using address-event- representation: a theoretical study and evaluation of the different algorithms

Image processing in digital computer systems usually considers the visual information as a sequence of frames. These frames are from cameras that capture reality for a short period of time. They are renewed and transmitted at a rate of 25-30 fps (typical real-time scenario). Digital video processing has to process each frame in order to obtain a filter result or detect a feature on the input. In stereo vision, existing algorithms use frames from two digital cameras and process them pixel by pixel until it is found a pattern match in a section of both stereo frames. Spike-based processing is a relatively new approach that implements the processing by manipulating spikes one by one at the time they are transmitted, like a human brain. The mammal nervous system is able to solve much more complex problems, such as visual recognition by manipulating neuron’s spikes. The spike-based philosophy for visual information processing based on the neuro-inspired Address-Event- Representation (AER) is achieving nowadays very high performances. In this work we study the existing digital stereo matching algorithms and how do they work. After that, we propose an AER stereo matching algorithm using some of the principles shown in digital stereo methodsMinisterio de Ciencia e Innovación TEC2009-10639-C04-02 (VULCANO)European Union (UE) FP7-248582 (CARDIAC

Sustained benefit of left ventricular remodelling after valve replacement for aortic stenosis

Background: Valve replacement for aortic stenosis (AS) determines negative ventricular remodelling. We used cross sectional and Doppler echocardiography to check how rapidly it occurs and to assess if these changes are sustained over time. Methods: We evaluated in 34 patients subjected to aortic valve replacement for AS morphological and functional (ejection fraction and E:A ratio) left ventricular data by echocardiography prior to surgery and 2 postoperative studies: early after surgery (pQ1) and at mid-term evolution (pQ2). Results: Left ventricular mass index was reduced at pQ1 (from 152 &#177; 47 g/m2 to 113 &#177; 31 g/m2; p < 0.01) as well as end-diastolic (from 51.3 mm to 48.3 mm; p < 0.03), end-systolic (from 32.2 mm to 29.4 mm; p < 0.02), interventricular septum (from 12.9 mm to 10.3 mm; p < 0.01), and posterior wall (from 12.5 mm to 11 mm; p < 0.01) dimensions. Left ventricular ejection fraction (from 61.2% to 65.2%; p < 0.04) and E:A ratio (from 0.94 to 0.98; p < 0.01) increased significantly at pQ1. There were no significant differences in measurements between pQ1 and pQ2. Conclusions: Aortic valve replacement surgery leads to a rapid negative left ventricular remodelling during the first 7 months, including a decrease in myocardial hypertrophy and an improvement in systolic and diastolic function. These beneficial hemodynamic changes are sustained for at least 3 years

Wpływ umiarkowanej miażdżycy tętnic wieńcowych na przebudowę lewej komory serca u chorych po wymianie zastawki aortalnej

Wstęp: Znaczenie miażdżycy tętnic wieńcowych (CA+) w procesie przebudowy lewej komory po wymianie zastawki aortalnej (AVR) z powodu izolowanej stenozy aortalnej (AS) jest wciąż przedmiotem badań. Celem pracy była ocena wpływu niepoddanych rewaskularyzacji umiarkowanych zmian miażdżycowych tętnic wieńcowych na odległy proces remodelingu lewej komory serca (LV) po AVR. Metody: Za pomocą koronarografii oceniono stopień nasilenia choroby wieńcowej u 66 pacjentów zakwalifikowanych do AVR i pozyskano dane echokardiograficzne dotyczące budowy i funkcji LV zarówno przed-, jak i pooperacyjnie (3 &#177; 1,2 roku). Wyniki: U pacjentów bez miażdżycy tętnic wieńcowych ustąpienie przerostu i całkowite odwrócenie remodelingu były większe niż w grupie chorych z miażdżycą, gdy porównano indeks masy LV (&#8211;55,8 &#177; 36 g/m2 v. &#8211;28,4 &#177; 34 g/m2; p = 0,004). Ponadto w grupie osób bez choroby wieńcowej obserwowano istotne zmniejszenie wymiarów LV [wymiar końcoworozkurczowy LV (LVEDD): &#8211;4,1 &#177; 7,4 mm v. &#8211;2,2 &#177; 8,3 mm; p = 0,04] oraz grubości ścian [przegrody międzykomorowej (IVS): &#8211;3,3 &#177; 2,6 mm v. &#8211;1,6 &#177; 2,2 mm; p = 0,01; i ściany tylnej (PWT): &#8211;2,1 &#177; 2,1 mm v. 0,6 &#177; 2,1 mm; p = 0,012]. Wnioski: Brak rewaskularyzacji umiarkowanych zmian miażdżycowych w nasierdziowych tętnicach wieńcowych u pacjentów poddanych AVR z powodu AS prowadzi w odległej obserwacji do zwolnienia procesu regresji przerostu lewej komory i zaburzenia odwrócenia remodelingu w analizie następujących parametrów: indeksu masy LV, LVEDD, IVS i PTW. (Folia Cardiologica Excerpta 2011; 6, 3: 162&#8211;167

Virtualización de la tutoría académica en alumnos de nuevo ingreso de magisterio

Se presenta un estudio evaluativo que trata de optimizar la tutoría académica centrada en la evaluación auténtica que se orienta hacia la construcción transversal de un proyecto profesional del estudiante de nuevo ingreso en el grado en magisterio. Se aborda un proceso hacia la virtualización de las tutorías académicas analizando las necesidades del estudiante, los requisitos competenciales de estudiantes y docentes universitarios y las buenas prácticas. An evaluative study is presented that tries to optimize the academic tutoring focused on the authentic evaluation that is oriented towards the transversal construction of a professional project of the new student of degree in primary education teaching. A process towards the virtualization of the academic tutorials is approached, analyzing the needs of the student, the competence requirements of students and university professors and the good practices