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A Dynamic Distributed-parameter Modeling Approach for Performance Monitoring of Oral Drug Delivery Systems
No full textRepresenting more than 50% of a worldwide pharmaceutical market of US$ 400 billions, oral drug delivery systems become naturally the focus of many studies. For almost half a century scientists have attempted to develop a theoretical model capable of predicting oral drug absorption in humans. From steady state or quasi-equilibrium models to complex and computationally intractable dynamic modeling approaches, numerous research efforts tried to address the problem of interest. Surprisingly though, no simple insightful first-principle-based dynamic modeling approaches have been reported in the literature. It is the purpose of the present work to provide a simple dynamic distributed-parameter modeling approach for performance monitoring of oral drug delivery systems.
As a consequence of the complexity of the gastrointestinal tract, drug oral bioavailability is influenced by many different parameters. These parameters range from the compound’s physicochemical properties, the physiological factors of the environment to other factors inherent in the drug form itself known as encapsulation factors. Physicochemical properties account for parameters such as drug stability, solubility or diffusivity. Furthermore, the environment, namely the gastrointestinal tract, influences the drug delivery process to the body with its pH, intestinal transit time and the different transport mechanisms that take place.
From a chemical engineering point of view, the human body’s anatomy can be analyzed and conceptually realized as a transport-reaction chemical system. Within the proposed modeling framework, the stomach is modeled as a non-ideal continuous-stirred tank reactor (CSTR) and the small intestine is the place where convection-diffusion occurs. The governing transport equations have been solved at steady state conditions in a small intestine represented by the lumen surrounded by its wall. The present work however develops a systematic dynamic first-principle-based distributed-parameter modeling framework where the time-dependent convection-diffusion-reaction model equations are analytically solved, offering the concentration profile in the small intestine lumen and in the wall from the moment the drug is administered until the complete absorption or disintegration of the drug particles.
Once the modeling work is performed, a thorough and insightful sensitivity analysis can be conducted in order to assess the impact of the different process parameters on drug bioavailability
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Membrane Reactor Modeling for Hydrogen Production through Methane Steam Reforming
No full textA mathematical modeling framework for the methane steam reforming reaction operating in steady state has been developed. Performances are compared between the classic catalytic packed bed reactor and a Pd-based catalytic membrane reactor.
Isothermal simulations on MATLAB © has first been conducted and show a higher performance of the membrane reactor over the packed bed reactor. Methane conversion of 1 can be reached for lower temperatures than used with industrial PBR, and better performances are shown for an increase in the operating pressure. Optimum conditions were defined for Temperature (500-600 Celsius), reaction side pressure (16-40 bars), membrane thickness (1-7 micrometers), steam/methane ratio (3-4), reactor length (5-10 meters) and permeate sweep ratio (20 or more). This model was validated by multiple recognized sources.
Adiabatic simulations were conducted in order to develop a mathematical model base for non-isothermal simulations. The membrane reactor is again showing a higher conversion of methane compared to the packed bed reactor, however the heat loss due to the membrane and the hydrogen leaving through the tube is decreasing the performances of the MR over the PBR compared to the isothermal case. Results show also that most of the reaction occurs at the very beginning of the reactor
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Transport-reaction Modeling of the Impedance Response of a Fuel Cell
No full textElectrochemical impedance spectroscopy (EIS) is a technique consisting of the application of a small perturbing current or voltage to an electrochemical system and measuring the response of the system. The response of the system can be described through the notion of impedance, Z, which is defined as the transfer function between the voltage and the current signal. By describing the impedance, one can gain insight into the interpretation of EIS experiments for the measurement of fundamental physical properties (eg diffusion coefficients).
The impedance responses of electrochemical systems have been described in the past as an arrangement of ideal equivalent-circuit elements. Simple lumped-parameter circuits and more complex finite-transmission-line circuits have been used in the past, but the disadvantage of this approach is the difficulty in interpreting the equivalent-circuit parameters in terms of fundamental properties. It is then interesting to determine impedance by describing mathematically the fundamental physical processes that govern the response of the system.
By describing and predicting analytically the impedance response induced by the perturbing current signal, one can: (i) gain considerable insight into the electrochemical process of interest, (ii) make explicit use of the modeling approach to address operational issues such as process design optimization, monitoring, diagnostics and control, and (iii) offer an interpretation to carefully designed EIS experiments for the measurement of fundamental physical properties such as diffusion coefficients or surface of active catalyst
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Nonlinear controller synthesis for complex chemical and biochemical reaction systems
No full textThe present research study is comprised of two main parts.
The first part aims at the development of a systematic system-theoretic framework that allows the derivation of optimal chemotherapy protocols for HIV patients. The proposed framework is conceptually aligned with a notion of continuous-time model predictive control of nonlinear dynamical systems, and results in an optimal way to control viral replication, while maintaining low antiretroviral drug toxicity levels. This study is particularly important because it naturally integrates powerful system-theoretic techniques into a clinically challenging problem with worldwide implications, namely the one of developing chemotherapy patterns for HIV patients that are effective and do not induce adverse side-effects.
The second part introduces a new digital controller design methodology for nonlinear (bio)chemical processes, that reflects contemporary necessities in the practical implementation of advanced process control strategies via digital computer-based algorithms. The proposed methodology relies on the derivation of an accurate sampled-data representation of the process, and the subsequent formulation and solution to a nonlinear digital controller synthesis problem. In particular, for the latter two distinct approaches are followed that are both based on the methodological principles of Lyapunov design and rely on a short-horizon model-based prediction and optimization of the rate of ""energy dissipation"" of the system, as it is realized through the time derivative of an appropriately selected Lyapunov function. First, the Lyapunov function is computed by solving the discrete Lyapunov matrix equation. In the second approach however, it is computed by solving a Zubov-like functional equation based on the system's drift vector field. Finally, two examples of a chemical and a biological reactor that both exhibit nonlinear behavior illustrate the main features of the proposed digital controller design method
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Adsorption Studies of Hazardous Air Pollutants in Microporous Adsorbents using Statistical Mechanical and Molecular Simulation Techniques
No full textThe primary goal of the research studies conducted was to apply statistical mechanical and computer simulation methods to describe the equilibrium behavior of hazardous dipolar/quadru-polar single-gases and mixtures confined in micro porous adsorbents. Statistical mechanical models capable of handling the energetic heterogeneity by complex electrostatic interactions between adsorbate–adsorbent and adsorbate-adsorbate electrostatic interactions were developed and studied. The heterogeneous pore shape and size of different adsorbents were taken into account by two different approaches described in the following paragraphs.
Under certain conditions, the use of Mean Field Perturbation Theories (MFPTs) is more attractive than Monte-Carlo (MC) simulations because of the enhanced physical insights that they offer, as well as very low computational times required. Existing literature shows that the applications of MFPTs for studying adsorption of polar molecules were limited due to the orientation dependency of the intermolecular potentials for electrostatic interactions, that in turn poses the challenging problem of seeking analytical expressions for the various thermodynamic functions involved. Furthermore, other existing approaches of accounting for complex electrostatic interactions through hydrogen bonding have limitations due to the requirement of parameter estimation related to radial distribution functions and the critical orientation values of molecules for hydrogen bonds, which are generally obtained through MC simulations and X-ray scattering techniques.
In the first stage of research efforts, an attempt was made to express angle-dependent intermolecular potentials in the form of angle-independent intermolecular potential terms by employing statistical averaging methods. In particular, the permanent dipole-dipole and permanent dipole-induced dipole intermolecular potentials were expressed as angle-averaged intermolecular potentials. Then, angle-averaged intermolecular potentials were used to predict water isotherms in nano-slit pores. Furthermore, the angle-averaged intermolecular potentials were used for a binary mixture of polar molecules (water-methanol) to predict the adsorption behavior in nano-slit pores. However, significant limitations of MFPTs arise when they are used for the study of adsorption in zeolites that exhibit irregular shaped cavities with surface heterogeneities. The latter certainly represent a future meaningful research direction. It should be pointed out, that the mean field approach allows us to predict equilibrium sorption properties in homogeneous adsorbents like graphitic carbon (slit), carbon nano tubes (cylinder) and highly siliceous faujasites (spherical) as they have regular shaped cavities. The applications of such kinds of theory remained limited due to the (generally) unknown distribution of functional sites on adsorbents of interests (mainly activated carbons and zeolites) and their locations in the adsorbent framework.
The second stage of research efforts focused on models capable of incorporating surface heterogeneities and addressing complex pore geometries. The models developed relied on Grand Canonical Monte-Carlo (GCMC) simulations. In particular, two types of GCMC simulations were carried out, namely molecular and atomistic MC simulations. Both techniques were applied to simulate sorption isotherms on zeolites and activated carbon to remove mercury chloride (quadrupole), hydrogen cyanide (HCN, dipole) and methyl ethyl ketone (MEK, dipole) from air.
The molecular based MC technique utilized molecular properties of the molecules namely dipole, quadrupole moments, molecular polarizability and molecule size (kinetic diameter). The molecule was considered to be a spherical shaped particle. The dispersion interactions were calculated using Vaan der Waals equation and electrostatic interactions were quantified through the multi-pole expansion method. This approach was used to simulate adsorption of HgCl2, HCN and MEK in zeolite NaX and activated carbon with functional sites namely carbonyl, hydroxyl and carboxyls. Simulation results indicated that HgCl2 sorption could be attributed to charge-induced dipole interactions for activated carbon, suggesting that sorbents with more number surface charges can be useful except for the case of carbonyls in which quadrupole moments plays a crucial role in reducing sorbent capacities, in turn implying that relative positions of positively and negatively charged cations are indeed important. However, for zeolite NaX, performance characteristics were primarily attributed to charge-quadrupole interactions and dispersion interactions. Moreover, zeolite-NaX performance characteristics for capturing HCN and MEK were attributed to dipole-Na interactions due to the relatively large dipole moments of the molecules under consideration. In the case of activated carbon, HCN sorption was governed by mainly charge-dipole and charge-induced dipole interactions, and hence, carbons with carboxyls seemed to perform better than hydroxyls and carbonyls. MEK sorption was influenced by dispersion interactions (due to the large polarizability of MEK) and charge-dipole interactions, which makes carbon with carbonyls more efficient rather than carbons with hydroxyls having the same charge densities. However, application of the aforementioned molecular approaches was limited to sorbents with regular shape cavities having some surface heterogeneity such as activated carbons. Finally, in order to account for sorbents with irregular shaped cavities, such as silicalite and mordenite, one needs to use atomistic MC simulations.
The atomistic MC technique utilizes appropriate atomic sizes and charges for the molecules under consideration to quantify intermolecular forces among the adsorbate molecules and the atoms of the zeolite framework as well as activated carbon. The dispersion interactions were calculated using the Van-Der Waals equation and electrostatic interactions were quantified through a standard Coulombic equation. The bond distances among atoms were kept fixed but variations in angular movement and dihedral/torsional movements were considered, and appropriate harmonic potentials were used to account for angle bending and torsional effects. The sorption performance was evaluated for mordenite, silicalite and zeolite beta for a Si/Al ratio of 47-197 for both an HCN and MEK system. The results of HCN/MEK sorption suggested that silicalite has greater capacity than that of mordenites .In the case of MEK Zeolite beta with sodium cations, performance was better than that of mordenites and silicalites. Sorption of HCN in silicalite was observed in straight and zigzag channels, and mainly attributable to hydrogen bonding among HCN molecules. The increase in sodium cations however decreases the capacity of silicalite, zeolite beta and mordenite slightly. The sorption of MEK in mordenite was mainly observed in an 12- and 8-member ring channel. It was found that an increase in sodium cations did not increase the sorption capacity of mordenite significantly as most of the cations in mordenite were located in an 8-member ring channel where MEK molecules can not be accommodated properly due to steric effects. However, the sorption of MEK in zeolite beta seemed to be influenced by the presence of sodium cations as most of the cations are at the intersection of two 12 member rings which provide sufficient space to orient MEK molecules at the intersection and maximize electrostatic interactions. The sorption of MEK in silicalite exhibited similar trends as in the case of mordenite, as all cations were at the intersection of straight and zigzag channels . Finally, in the last Section of the Thesis, a comparative assessment was made of all three approaches in terms of their significance in applications and the ease in applying them
Unresolved Issues Regarding Homework Assignments in Cognitive and Behavioural Therapies: An Expert Panel Discussion at AACBT
No full textThis article presents a panel discussion on the integration of homework assignments into cognitive behaviour therapy sessions. The panel comprised experts in research and practice who had been invited as keynote presenters for the 32nd National Conference for the Australian Association of Cognitive and Behaviour Therapy. Experts responded to questions about the definition of homework, the mechanism by which homework produces its effects, and the relative importance of homework adherence for effective therapy. Interwoven through the discussion was an emphasis on a collaborative approach to homework, as well as specific recommendations for the integration of homework into sessions. Selected case illustrations were also discussed
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Automatic processes in eating behavior : understanding and overcoming food cue-reactivity
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