Conceptualisation, Development, Fabrication and In Vivo Validation of a Novel Disintegration Tester for Orally Disintegrating Tablets

Disintegration time is the key critical quality attribute for a tablet classed as an Orally Disintegrating Tablet (ODT). The currently accepted in vitro testing regimen for ODTs is the standard United States Pharmacopeia (USP) test for disintegration of immediate release tablets, which requires a large volume along with repeated submergence of the dosage form within the disintegration medium. The aim of this study was to develop an in vivo relevant ODT disintegration test that mimicked the environment of the oral cavity, including lower volume of disintegration medium, with relevant temperature and humidity that represent the conditions of the mouth. The results showed that the newly developed Aston test was able to differentiate between different ODTs with small disintegration time windows, as well as between immediate release tablets and ODTs. The Aston test provided higher correlations between ODT properties and disintegration time compared to the USP test method and most significantly, resulted in a linear in vitro/in vivo correlation (IVIVC) (R 2 value of 0.98) compared with a "hockey stick" profile of the USP test. This study therefore concluded that the newly developed Aston test is an accurate, repeatable, relevant and robust test method for assessing ODT disintegration time which will provide the pharmaceutical industry and regulatory authorities across the world with a pragmatic ODT testing regime

Formulation and Bioequivalence Testing of Fixed-Dose Combination Orally Disintegrating Tablets for the Treatment of Tuberculosis in the Paediatric Population

Tuberculosis (TB) is believed to affect around 10 million people worldwide. Treatment for TB includes isoniazid and rifampicin, with fixed-dose combination (FDC) recommended for improved patient compliance. Similarly, orally disintegrating tablets (ODTs) are an increasingly popular dosage form that aid compliance since they do not require swallowing. In this study ODTs of isoniazid and rifampicin, either as discrete or FDC doses, were formulated and bioequivalence between single and combination doses compared using in vitro and in silico approaches. Dissolution profiles were compared using FDA advised difference (f 1) and similarity (f 2) testing in biorelevant media. Rifampicin release from FDCs decreased by approximately 15% in fed-state media (failed f 1 and f 2), which was attributed to enhanced rifampicin degradation in the presence of isoniazid at lower pH. Apparent permeability (P app) values derived from Caco-2 transport studies were included alongside dissolution results into a physiologically based pharmacokinetic (PBPK) model, to simulate in vivo bioavailability in healthy subjects. Models showed no difference in bioavailability between formulations or dosing (fasted or fed) state, despite the failures in dissolution-based bioequivalence testing, highlighting shortcomings in f 1 and f 2 assessment and the strength of PBPK models

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Corrélation des conditions de production et des propriétés physicochimiques de la cellulose microcristalline avec sa fonctionnalité en compression directe

Grâce à ses propriétés uniques permettant d’augmenter la dureté et l’intégrité des comprimés, la cellulose microcristalline (MCC) est un des excipients les plus importants en compression directe. La compression directe reste le procédé le plus économe pour produire de grandes quantités de comprimés, cependant son efficacité dépend directement de la qualité et des propriétés des matières premières. Comme préconisé par les principes du « quality-by-design » (QbD), il est nécessaire de comprendre et de contrôler la variabilité des excipients afin de développer et de produire des formes médicamenteuses solides de qualité.Le but premier de cette étude est de déterminer et comprendre la variabilité des propriétés physicochimiques de la MCC et des conditions de fabrication des deux sites de production de FMC Health and Nutrition, à savoir Cork (Irlande) et Newark, DE (USA). A cette fin, un nombre total de 84 échantillons de MCC 102 et de 75 échantillons de MCC 101 ont été récoltés dans un premier temps par les deux sites de productions et ont ensuite été caractérisés de manière approfondie. Les propriétés physicochimiques des échantillons provenant de Cork et de Newark étaient comparables à celles décrites par des centaines de certificats d’analyse ainsi qu’aux valeurs mesurées à partir de milliers d’échantillons prélevés en fin de production. Cependant la teneur en eau des échantillons récoltés par Newark était plus élevée, suggérant une adsorption de l’humidité plus importante que les échantillons typiquement prélevés pour le control qualité. Une distinction entre les deux sites de production a pu être établie sur base des conditions d’hydrolyse et de certaines propriétés physicochimiques de leurs MCC, comme par exemple la densité vrac des MCC 101 et la granulométrie des MCC 102.La répétabilité et la reproductibilité de la mesure de comprimabilité ont été confirmées grâce à une étude Gauge R&R et à la compression de dix MCC en triplicata par trois opérateurs. La reproductibilité des mesures de comprimabilité et d’écoulement a également été établie par l’évaluation de celluloses de références durant toute la durée de cette étude.Les études de comprimabilité de la MCC ont confirmé l’importance de plusieurs paramètres critiques précédemment identifiés, à savoir la granulométrie et la teneur en eau. Ce travail a également démontré l’importance de la densité des MCC sur leur comprimabilité, et en particulier de la densité tassée pour la MCC 102 et de la densité vrac pour la MCC 101. Les causes principales de la variation de la comprimabilité des MCC ont pour origine les variations du type de pulpes utilisées, de la température de séchage et des conditions d’hydrolyse.Les études d’écoulement ont mis en évidence l’importance de la granulométrie des MCC. L’indice de compressibilité a permis d’identifier des différences entre l’écoulement des MCC 102 originaires de Cork ou de Newark. D’autres caractéristiques comme la teneur en eau, le degré de polymérisation et la conductivité ont également influencé l’indice de compressibilité. L’uniformité du poids des comprimés produits sur une presse excentrique a été corrélée avec la densité vraie et la conductivité des dispersions de MCC 102 ainsi qu’avec la densité vrac des MCC 101. La variation des propriétés d’écoulement des MCC est due principalement à l’utilisation de plusieurs atomiseurs et de plusieurs sortes de pulpes.Pour conclure, une corrélation statistiquement significative a été établie entre l’indice de compressibilité et le paramètre a de Kawakita, un des descripteurs de compressibilité les plus importants

Uses of collaborative platforms, a comprehensive study : the case of BlaBlaCar

International audienceOur researches focus on users of collaborative platforms, including BlaBlaCar. Our hypothesis is that the qualitative method of the ideal type used in sociology can provide more conclusive results than quantitative economic analysis. We determined two ideal types as defined by sociologist Max Weber and compared our results with a recent quantitative economic study. It turns out that the qualitative approach allows a deeper and more comprehensive approach of collaborative platforms and takes a better account of social and ecological aspects. It is likely to provide decision-makers with a wider insight on major issues of collaborative platforms for their users

Superoverlay Deployment in Grid-enabled Image Processing

SuperOverlays are image pyramid constructs for use in visualisation of client side imagery in the Google Earth (GE) virtual globe viewer. SuperOverlays combine portable image formats, such as JPEG, PNG or TIFF, with geographical metadata tagging in KML files. This has the fortunate sideeffect that SuperOverlays can be easily served via standard web servers. Furthermore, it is relatively simple to programmatically access relevant parts of the SuperOverlay via their URI. This, then, allows the use of SuperOverlays in image processing, which can optionally be supported with a grid computing set-up. Presenting image processing output is facilitated by collecting grid node outputs in a SuperOverlay structure. In this paper, we demonstrate the use of a texture algorithm with SPOT-5 optical satellite data for benchmarking of the grid-enabled SuperOverlay processing against current practice single platform CPU processing. We discuss the impact of our solution on the feasibility for an image processing service configuration that can run in a client-server environment, possibly using GE as a user interface.JRC.DG.G.2-Global security and crisis managemen

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Van Elslander, AntoninVan Elslander, AntoninVan Elslander, AntoninVan Elslander, AntoninVan Elslander, AntoninVan Elslander, AntoninVan Elslander, AntoninVan Elslander, Antoni

Distributed Geospatial Data Processing Functionality to Support Collaborative and Rapid Emergency Response

This paper presents a novel approach to integrate the latest generation very high-resolution earth observation imagery into the operational workflow of geospatial information support for emergency response actions. The core concept behind this approach is the implementation of an image pyramid structure that allows each image tile to be addressed separately.We propose a novel way to collate geospatial feature data from distributed sources and integrate them in visualization and image processing. The system components enable rapid collaborative mapping, support for in situ data collection, customized on-demand image processing, and geospatial data queries and near instantaneous map visualization. We adapt functional software modules that are available in the public and open source domain. The approach is demonstrated with a test case in a rapid damage assessment scenario using very high-resolution optical satellite QuickBird and IKONOS imagery over Southern Lebanon from 2006.JRC.G.2-Global security and crisis managemen