Development of a biorelevant dynamic model of human proximal colon: a tool for designing colon – specific drug delivery systems

A novel Dynamic Colon Model (DCM) that represents the anatomy and physiology of the human proximal colon was developed. Analysis of the hydrodynamics was performed using Positron Emission Particle Tracking (PEPT) system and Positron Emission Tomography (PET). The pressures generated by the wall motion of the DCM tube compared with the available published in vivo data. The hydrodynamics in USP 2 dissolution apparatus were also assessed using Particle Image Velocimetry (PIV) and Planar Induced Fluorescence (PLIF). Areal distribution and individual striation methods showed high mixedness level close to tip. PEPT experiments were performed using particles of different buoyancy. Use of different particles gave different results in terms of velocities and residence times within the DCM tube. PET images showed that antegrade propagating waves of amplitude lower than the minimum threshold used in vivo studies were associated with flow episodes. In addition, flow episodes can occur which are not related to the wall motion. Dissolution profiles of theophylline, a high water soluble drug, released from a hydrophilic matrix obtained at viscous shear thinning media, mimicking the dewatering process in the human colon. The novel DCM provides a realistic colonic environment, enabling biorelevant in vitro assessment of the in vivo performance of dosage forms

Development of a biorelevant dynamic model of human proximal colon: a tool for designing colon – specific drug delivery systems

A novel Dynamic Colon Model (DCM) that represents the anatomy and physiology of the human proximal colon was developed. Analysis of the hydrodynamics was performed using Positron Emission Particle Tracking (PEPT) system and Positron Emission Tomography (PET). The pressures generated by the wall motion of the DCM tube compared with the available published in vivo data. The hydrodynamics in USP 2 dissolution apparatus were also assessed using Particle Image Velocimetry (PIV) and Planar Induced Fluorescence (PLIF). Areal distribution and individual striation methods showed high mixedness level close to tip. PEPT experiments were performed using particles of different buoyancy. Use of different particles gave different results in terms of velocities and residence times within the DCM tube. PET images showed that antegrade propagating waves of amplitude lower than the minimum threshold used in vivo studies were associated with flow episodes. In addition, flow episodes can occur which are not related to the wall motion. Dissolution profiles of theophylline, a high water soluble drug, released from a hydrophilic matrix obtained at viscous shear thinning media, mimicking the dewatering process in the human colon. The novel DCM provides a realistic colonic environment, enabling biorelevant in vitro assessment of the in vivo performance of dosage forms

In vitro models to evaluate ingestible devices:present status and current trends

Orally ingestible medical devices offer significant opportunity in the diagnosis and treatment of gastrointestinal conditions. Their development necessitates the use of models that simulate the gastrointestinal environment on both a macro and micro scale. An evolution in scientific technology has enabled a wide range of in vitro, ex vivo and in vivo models to be developed that replicate the gastrointestinal tract. This review describes the landscape of the existing range of in vitro tools that are available to characterize ingestible devices. Models are presented with details on their benefits and limitations with regards to the evaluation of ingestible devices and examples of their use in the evaluation of such devices is presented where available. The multitude of models available provides a suite of tools that can be used in the evaluation of ingestible devices that should be selected on the functionality of the device and the mechanism of its function

Ο ρόλος των Κέντρων Εξυπηρέτησης Πολιτών στη Δημόσια Διοίκηση, στην Ελλάδα και το εξωτερικό

Τα τελευταία έτη η ανάγκη επιτάχυνσης της διαδικασίας εκσυγχρονισμού του κράτους και της δημόσιας διοίκησης είναι επιτακτική περισσότερο από ποτέ. Σύμμαχος στην προσπάθεια αυτή είναι η ηλεκτρονική διακυβέρνηση, η αξιοποίηση δηλαδή των Τεχνολογιών Πληροφορικής και Επικοινωνιών (ΤΠΕ) στις δημόσιες υπηρεσίες, σε συνδυασμό με τις οργανωτικές αλλαγές και τις νέες δεξιότητες του προσωπικού. Μία από τις πιο αντιπροσωπευτικές, σήμερα, υπηρεσίες άσκησης Ηλεκτρονικής Δημόσιας Διοίκησης αποτελούν τα Κέντρα Εξυπηρέτησης Πολιτών (ΚΕΠ). Σκοπός της παρούσας διπλωματικής εργασίας είναι η αποτύπωση του βαθμού συμβολής του θεσμού των ΚΕΠ στην αποδοτικότητα και την αποτελεσματικότητα του δημοσίου τομέα. Ερευνάται η ύπαρξη και ο τρόπος λειτουργίας αντίστοιχων Υπηρεσιών Μιας Στάσης (One Stop Shop) και Ψηφιακών Δημοσίων Υπηρεσιών σε ευρωπαϊκό επίπεδο. Επιπρόσθετα, αξιολογούνται και συγκρίνονται οι επιδόσεις τους. Πιο συγκεκριμένα, στην εργασία αρχικά γίνεται αναφορά στην προσαρμογή της Δημόσιας Διοίκησης στις αρχές και τους κανόνες της Διοίκησης Ολικής Ποιότητας, καθώς και τη χρήση τεχνικών βελτίωσης της ποιότητας. Στη συνέχεια επιχειρείται η ιστορική αναδρομή των βασικότερων ευρωπαϊκών στρατηγικών και δράσεων για την ανάπτυξη της ηλεκτρονικής διακυβέρνησης. Επιπλέον περιγράφονται τα σημαντικότερα προγράμματα και δράσεις εφαρμογής της Ηλεκτρονικής Διακυβέρνησης στην Ελλάδα. Ακολουθεί η αναλυτική παρουσίαση της εξέλιξης του θεσμού των ΚΕΠ, των χαρακτηριστικών και αρμοδιοτήτων του, καθώς επίσης της λειτουργίας του ως Ενιαία Κέντρα Εξυπηρέτησης (ΕΚΕ). Επιπροσθέτως, αναδεικνύονται τα πλεονεκτήματα της εν λόγω υπηρεσίας και επισημαίνονται οι αδυναμίες. Στην κατεύθυνση αυτή, παρατίθενται διεθνή παραδείγματα καλών πρακτικών Ηλεκτρονικής Διακυβέρνησης στη Δημόσια Διοίκηση και συγκρίνονται οι επιδόσεις χωρών σε ευρωπαϊκό και εθνικό επίπεδο με τη χρήση κατάλληλων δεικτών. Η διατριβή ολοκληρώνεται με την εξαγωγή συμπερασμάτων και τη διατύπωση σχετικών προτάσεων. Η μεθοδολογία που ακολουθήθηκε περιλαμβάνει βιβλιογραφική έρευνα, μελέτη και σχολιασμό άρθρων, εκθέσεων και νομοθεσίας, ανάλυση SWOT, σύγκριση δεικτών και αναζήτηση ηλεκτρονικών δημοσιεύσεων στο διαδίκτυο. Η έρευνα, η παρουσίαση και η σύγκριση βέλτιστων πρακτικών εφαρμογής ηλεκτρονικής διακυβέρνησης στηρίχθηκε στη χρήση πινάκων και διαγραμμάτων και τη σύνδεση με επίσημες διαδικτυακές πύλες.The last few years the need to accelerate the modernization of the state and public administration is more urgent than ever. This effort is reinforced by e-Government which makes use of Information and Communication Technology (ICT) in Public Services and combines the organizational changes and the staff’s new skills. Νowadays, the Citizens Service Centres (CSC) represents mostly the implementation of Electronic Public Administration. Τhe aim of this thesis is to show up the CSC’s importance to the productivity and effectiveness of the public sector. In this direction, the way that equivalent services (One Stop Shop) and Digital Public Services operate is being searched thoroughly on European level, while their progress is being estimated and compared to each other. In particular, the adaptation of Public Administration to the principles and rules of Total Quality Management and the use of quality improvement tools, initially stated in the thesis. Afterwards, a historical overview of European strategies and actions for the development of the e-Government is attempted, together with a description of the most significant programs and actions of e-Government in Greece. Τhe development of the institution of the CSC, its features and competences, as well as its operation as Points of Single Contact (PSC) are expanded in detail while the advantages and its drawbacks are pointed out. International examples of best practices of e-Governance in Public Administration are shown alongside and the progress of countries is compared on European and National level by means of indicators. Τhe thesis is completed by presenting conclusions and submitting appropriate proposals. The methodology followed includes bibliographic research, study and comment on articles, essays and legislation, SWOT Analysis, comparison of indicators and search for electronic publications on the internet. Tables and charts as well as the connection to formal internet portals have been used to research, present and compare the practices of the implementation of Electronic Administration

Dissolution profile of theophylline modified release tablets, using a biorelevant Dynamic Colon Model (DCM)

AbstractThe human proximal colon has been considered a favourable site to deliver drugs for local and systemic treatments. However, modified dosage forms face a complex and dynamically changing colonic environment. Therefore, it has been realized that in addition to the use of biorelevant media, the hydrodynamics also need to be reproduced to create a powerful in vitro dissolution model to enable in vivo performance of the dosage forms to be predicted.A novel biorelevant Dynamic Colon Model (DCM) has been developed which provides a realistic environment in terms of the architecture of the smooth muscle, the physical pressures and the motility patterns occurring in the proximal human colon. Measurements of pressure inside the DCM tube confirmed a direct association between the magnitude of the pressure signal with the occlusion rate of the membrane and the viscosity of the fluid.The dissolution profile and the distribution of the highly soluble drug, theophylline, were assessed by collecting samples at different locations along the DCM tube. Differences in the release rates of the drug were observed which were affected by the sampling point location, the viscosity of the fluid and the mixing within the DCM tube. Images of the overall convective motion of the fluid inside the DCM tube obtained using Positron Emission Tomography enabled relation of the distribution of the tracer to likely areas of high and low concentrations of the theophylline drug.This information provides improved understanding of how extensive phenomena such as supersaturation and precipitation of the drug may be during the passage of the dosage form through the proximal colon

Use of PLIF to assess the mixing performance of small volume USP 2 apparatus in shear thinning media

AbstractPlanar Laser Induced Fluorescence (PLIF) was used to assess mixing in small volume USP 2 dissolution apparatus for a range of viscous fluids which mimic gastrointestinal media, especially in the fed state. The release into the media from a specially prepared tablet containing Rhodamine 6G dye was tracked in time and the areal distribution method developed by Alberini et al. (2014a) was implemented to characterise the mixing performance. The distributions of the individual striations for selected mixing levels were also presented. These findings illustrate the poor mixing performance of the apparatus resulting in high variance of the dissolution data when working with viscous media. Analysis of data using CoV gives misleading results for the mixing performance of the small volume USP 2 dissolution apparatus. The results showed that the best mixing was mainly located above the blade and close to the wall, i.e. in the region where intensive motion takes place. This work presents important guidelines and precautions for choosing the proper sampling point for a wide range of liquid viscosities to minimize the variability of the dissolution data

Corporate Income Tax Compliance Costs and their Determinants: Evidence from Greece

This paper examines the corporate income tax compliance costs and their determinants by analyzing survey and financial statements data from firms operating in Greece. We find that corporate tax compliance costs are of considerable size and vary with several firm-specific characteristics, including the firm’s size, its age, the sector in which it operates, its location and its legal form. The paper intends to raise awareness regarding the impact of tax compliance costs, especially for countries, such as Greece, that were significantly affected by the economic and financial crisis

Explaining Corporate Effective Tax Rates Before and During the Financial Crisis: Evidence from Greece

This paper examines the determinants of the variability in corporate effective tax rates before and after the beginning of the financial crisis in Greece. Analyzing firm-level data for the period between 2000 - 2014, we find strong evidence that specific firm characteristics including firm size, financial leverage, capital and inventory intensity influence the level of corporate effective tax rates. Our results also indicate that corporate effective tax rates and their association with the firm-specific characteristics were significantly influenced in the sub-period after the beginning of the financial crisis. Our findings may have important implications both for policy makers and firms

Explaining Corporate Effective Tax Rates Before and During the Financial Crisis: Evidence from Greece

This paper examines the determinants of the variability in corporate effective tax rates before and after the beginning of the financial crisis in Greece. Analyzing firm-level data for the period between 2000 - 2014, we find strong evidence that specific firm characteristics including firm size, financial leverage, capital and inventory intensity influence the level of corporate effective tax rates. Our results also indicate that corporate effective tax rates and their association with the firm-specific characteristics were significantly influenced in the sub-period after the beginning of the financial crisis. Our findings may have important implications both for policy makers and firms