76,893 research outputs found

    Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

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    The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties

    Unobserved Heterogeneity in Multiple-Spell Multiple-States Duration Models

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    In survival analysis a large literature using frailty models, or models with unobserved heterogeneity, exist. In the growing literate on multiple spell multiple states duration models, or multistate models, modeling this issue is only at its infant phase. Ignoring unobserved heteogeneity can, however, produce incorrect results. This paper presents how unobserved heterogeneity can be incorporated into multistate models, with an emphasis on semi-Markov multistate models with a mixed proportional hazard structure. First, the aspects of frailty modeling in univariate (proportional hazard, Cox) duration models are addressed and some important models with unobserved heterogeneity are discussed. Second, the domain is extended to modeling of parallel/clustered multivariate duration data with unobserved heterogeneity. The implications of choosing shared or correlated unobserved heterogeneity is highlighted. The relevant differences with recurrent events data is covered next. They include the choice of the time scale and risk set which both have important implications for the way unobserved heterogeneity influence the model. Multistate duration models can have both parallel and recurrent events. Incorporating unobserved heterogeneity in multistate models, therefore, brings all the previously addressed issues together. Although some estimation procedures are covered the emphasis is on conceptual issues. The importance of including unobserved heterogeneity in multistate duration models is illustrated with data on labour market and migration dynamics of recent immigrants to The Netherlands.multiple spell multiple state duration, mixed proportional hazard, multistate model, unobserved heterogeneity, frailty

    A Practical Method to Estimate Information Content in the Context of 4D-Var Data Assimilation. I: Methodology

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    Data assimilation obtains improved estimates of the state of a physical system by combining imperfect model results with sparse and noisy observations of reality. Not all observations used in data assimilation are equally valuable. The ability to characterize the usefulness of different data points is important for analyzing the effectiveness of the assimilation system, for data pruning, and for the design of future sensor systems. This paper focuses on the four dimensional variational (4D-Var) data assimilation framework. Metrics from information theory are used to quantify the contribution of observations to decreasing the uncertainty with which the system state is known. We establish an interesting relationship between different information-theoretic metrics and the variational cost function/gradient under Gaussian linear assumptions. Based on this insight we derive an ensemble-based computational procedure to estimate the information content of various observations in the context of 4D-Var. The approach is illustrated on linear and nonlinear test problems. In the companion paper [Singh et al.(2011)] the methodology is applied to a global chemical data assimilation problem
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