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Belton, Alexander C. R. "A matrix formulation of quantum stochastic calculus." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301800.
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We develop the theory of chaos spaces and chaos matrices. A chaos space is a Hilbert space with a fixed, countably-infinite, direct-sum decomposition. A chaos matrix between two chaos spaces is a doubly-infinite matrix of bounded operators which respects this decomposition. We study operators represented by such matrices, particularly with respect to self-adjointness. This theory is used to re-formulate the quantum stochastic calculus of Hudson and Parthasarathy. Integrals of chaos-matrix processes are defined using the Hitsuda-Skorokhod integral and Malliavin gradient,following Lindsay and Belavkin. A new way of defining adaptedness is developed and the consequent quantum product Ito formula is used to provide a genuine functional Ito formula for polynomials in a large class of unbounded processes, which include the Poisson process and Brownian motion. A new type of adaptedness, known as $\Omega$-adaptedness, is defined. We show that quantum stochastic integrals of $\Omega$-adapted processes are well-behaved; for instance, bounded processes have bounded integrals. We solve the appropriate modification of the evolution equation of Hudson and Parthasarathy: $U(t)=I+\int_{0}^{t}E(s)\mathrm{d}\Lambda(s)+F(s)\mathrm{d} A(s)+ G(s)U(s)\mathrm{d} A^{\dagger}(s)+H(s)U(s)\mathrm{d} s, $ where the coefficients are time-dependent, bounded, $\Omega$-adapted processes acting on the whole Fock space. We show that the usual conditions on the coefficients, viz. $(E,F,G,H)=(W-I,L,-WL^{*},iK+\mbox{$\frac{1}{2}$}LL^{*})$ where $W$ is unitary and $K$ self-adjoint, are necessary and sufficient conditions for the solution to be unitary. This is a very striking result when compared to the adapted case.
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Benkaddour, Ilham. "Matrix Formulation of Fractional Supersymmetry and q-Deformation." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-53038.
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Sivess, Andrew Gregory. "Chebyshev polynomial based finite element stiffness matrix formulation." Diss., Connect to online resource, 2005. http://wwwlib.umi.com/cr/colorado/fullcit?p1427762.
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Wallin, Marina. "Multiple electromagnetic scattering by spheres using the T-matrix formulation." Thesis, Umeå universitet, Institutionen för fysik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-105606.
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Low observable technology is used in order to prevent detection, or to delay detection. Radar cross section is an important parameter in aircraft survivability since it measures how detectable an object is with radar. To find the radar cross section Maxwell's equations are solved numerically in the time-domain using a finite difference scheme. This numerical method called Finite Difference Time Domain is very suitable for structures including complex materials. However, this numerical method needs to be verified for large scale simulations, due to numerical dispersion errors. Therefore it is desirable to verify the accuracy of the numerical simulations. In this project, the analytical solution to the multiple scattering by two spheres is implemented using the T-matrix formulation. The analytical solution to the scattering problem is first validated with the analytical Mie-series solution then compared to the Finite Difference Time Domain implementation. The results imply that the difference between the numerical and analytical solution is larger for higher frequencies and larger computational volumes.<br>Smygteknik används för att förhindra detektering, eller för att fördröja detektion av ett flygplan. Radarmålarea är en viktig parameter för skyddsprestanda hos flygplan eftersom den mäter hur detekterbar ett föremål är med radar. För att hitta radarmålarean löses Maxwells ekvationer numeriskt i tidsdomänen med hjälp av ett finit differensschema. Den numeriska metoden som kallas Finita differensmetoden i tidsdomän, är mycket lämplig för strukturer med komplexa material. Den numeriska metoden behöver valideras för storskaliga simuleringar eftersom det förekommer felaktigheter på grund av den numeriska dispersionen. Därför är det önskvärt att kontrollera riktigheten av de numeriska simuleringarna. I detta projekt, är den analytiska lösningen till multipelspridning av två sfärer implementerad med hjälp av T-matrismetoden. Den analytiska lösningen på spridningsproblemet valideras först mot den analytiska Mie-serielösningen och sedan jämförs den med resultatet av simuleringarna med Finita differensmetoden i tidsdomän. Resultaten antyder att skillnaden mellan den numeriska och analytiska lösningen är större för högre frekvenser och större beräkningsvolymer.
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Arjun, Jessica. "The development and assessment of both a separate, once-daily modified release matrix formulation of metoprolol tartrate and a combination formulation with hydrochlorothiazide." Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1003220.
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The use of controlled release dosage forms has increased significantly in recent years as they result in increased patient compliance and higher therapeutic efficiency. This research focused on the development of a once daily dosage form that could be used for the treatment of hypertension. Both a separate sustained release dosage of metoprolol tartrate and a combination dosage form that included both an immediate release hydrochlorothiazide and a sustained release metoprolol component, were developed and evaluated. A matrix tablet, consisting of an ethylcellulose ranulation of metoprolol tartrate compressed into a hydrophilic hydroxypropyl methylcellulose polymer matrix, effectively sustained metoprolol release over a 22-hour experimental period. A multiparticulate combination dosage form that consisted of six coated mini matrix tablets of metoprolol and a powder blend of hydrochlorothiazide packed into a gelatin capsule, displayed zero order release kinetics for metoprolol release over 22 hours (r2=0.9946). The release of hydrochlorothiazide was found to be comparable to that of a commercially available product tested. Differential Scanning Calorimetry was used to identify possible incompatibilities between MPTA and excipients initially, and long term stability testing was used to assess to behaviour of the dosage form. Dissolution testing of the dosage forms was performed using USP Apparatus III, which was found to be more discriminating between the batches assessed. Dissolution curves were evaluated for similarity and difference using f1 and f2 fit factors. Samples were analyzed using a high performance liquid chromatographic method that was developed and validated for the simultaneous determination of the compounds of interest. Various factors influencing drug release from the developed dosage forms were assessed and recommendations for further optimization of the formulation are made. Factors evaluated included the quantity of granulating fluid, matrix polymer content, drug load and process variables, including drying time and compression force. The influence of various coating levels on drug release was assessed and none of the levels assessed were found to adequately retarded drug release over a 22-hour period. Combinations of tablets coated to different levels allowed for the successful development of a sustained release metoprolol component, which could be included into the combination dosage form.
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Novikov, Alexey. "Path integral formulation of dissipative quantum dynamics." Doctoral thesis, [S.l. : s.n.], 2005. http://archiv.tu-chemnitz.de/pub/2005/0050.
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Fischer, André [Verfasser]. "Matrix model formulation of LS-covariant noncommutative quantum field theories on Minkowski spacetime / André Fischer." Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover, 2011. http://d-nb.info/1011399016/34.
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Cheboyina, Sreekhar. "Design and development of a novel freeze pelletization technique : formulation, characterization and evaluation of matrix pellets /." Full text available from ProQuest UM Digital Dissertations, 2006. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1260798651&SrchMode=1&sid=4&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1193083907&clientId=22256.
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Grund, Julia [Verfasser]. "Formulation and evaluation of water-insoluble matrix drug delivery systems and modelling of drug release / Julia Grund." Berlin : Freie Universität Berlin, 2013. http://d-nb.info/1037343158/34.
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Tsoi, Eric W. "Formulation Development of a Polymer-Drug Matrix with a Controlled Release Profile for the Treatment of Glaucoma." DigitalCommons@CalPoly, 2013. https://digitalcommons.calpoly.edu/theses/1134.
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Glaucoma is the leading cause of blindness in the United States accounting for 9-12% of all cases of blindness. Currently, the front line treatment for glaucoma are prostaglandins that may have to be taken up to several times a day. Even with proper treatment, roughly 11% of the patients using the treatment are non-compliant and lose their vision. In this project, ForSight Laboratories has developed a pharmaceutical drug delivering implant with the capability of sustaining long-term release of a prostaglandin as a new way to treat the condition. This project reports the product development of a polymer drug matrix with a controlled release in order to better treat glaucoma. Accompanying product development, a mathematical model was created in order to strengthen the understanding of the dosage profile and to predict long term dosages.
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Boudendouna, Abdel Hakim. "Méthodologie de la formulation d’une forme orale solide à libération prolongée." Thesis, Toulouse, INPT, 2010. http://www.theses.fr/2010INPT0052/document.
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L'objectif de ce travail a été l'utilisation d'une méthodologie de formulation des formes à libération prolongée. Le choix de «matrices hydrophiles» a été fait en raison de l'intérêt et de l'importance des travaux qui lui sont consacrés, mais surtout en raison de la possibilité d'utilisation de la technologie simple de fabrication des comprimés par compression directe.Le principe actif choisi est le diclofenac de sodium, un anti-inflammatoire largement utilisé dont la molécule est tombée dans le domaine public. Utilisé à raison de 100 mg par comprimé. La première partie bibliographique résume l'intérêt des formes à libération prolongée, décrit les différentes formes galéniques existantes pour la voie orale et fait le point sur les formules et les propriétés des agents matriciels hydrophiles parmi les plus utilisés, notamment les éthers de celluloses, hydroxypropymethylcellulose (METOLOSES®) (1). Dans la partie expérimentale, nous avons réalisé les différentes étapes nécessaires au développement d'une forme à libération prolongée qui correspondant aux étapes classiques de pré-formulation, formulation et optimisation. Dans une première étape d'essais préliminaires nous avons étudiés le comportement d'un point de vue pharmacotechnique des matières premières utilisés seuls et en mélange. Ce qui a permis de faire des orientations en ce qui concerne les différents types de METOLOSES, la nature du diluant, et leurs concentrations. Dans une deuxième étape, nous avons réalisé un premier plan d'expériences de criblage des facteurs, qui permet de déterminer le poids de chacun et leurs éventuelles interactions. Ce qui nous a permis de conclure sur l'effet des différents facteurs en formulation. Dans une troisième étape, nous avons réalisé un deuxième plan d'expériences d'optimisation de la formulation en utilisant un plan composite centré constitué de 9 expériences ce qui a permis de sélectionner une zone de formules optimales. Enfin, la réalisation d'une formule optimale nous a permis de confirmer les résultats obtenus dans les travaux de développement et dont l'objectif été une libération sur 12 heures<br>The objective of this work was the use of a formulation methodology of prolonged release dosage forms. The choice of “hydrophilic matrices” was done because of the interest and the numbered works which is devoted to it, but also for the use of a simple manufacture technology by direct compression. The selected active pharmaceutical ingredient is one of the most largely used nonsteroidial anti-inflammatory drug, the sodium diclofenac which is out of patent and used at 100 Mg per tablet. The first bibliographical part summarizes the interest of the prolonged release dosage forms, described the existing oral dosage forms and gives a progress report on the formulas and the properties of hydrophilic matrices agents among most used, in particular the cellulose ethers, hydroxypropymethylcellulose (METOLOSES®) (1). In the experimental part, we carried out the various steps necessary to the development of a prolonged release dosage form which correspond to the traditional steps of pre-formulation, formulation and optimization. In a first step of pharmaceutics preliminary tests we studied the behavior of raw materials used alone and in mixture. What made orientations with regard to the various types of METOLOSES, the nature of diluents, and their concentrations. In a second step, we carried out a first screening factors experimental design, which enabled us to conclude on the effect of the various factors in formulation. In a third step, we carried out a second optimization experimental design using a centered composite plan consisted of 9 experiments which lead us to define a space design of optimal formulas. Lastly, the manufacture of a formula from the design space enabled us to confirm the results to development work and for which the objective was a sustained release over 12 hours
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Ghorbel, Olfa. "Formulation et mise en oeuvre d’un élément continu de plaque sandwich et de plaque multicouche." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLC020/document.
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Cette thèse traite du développement d’un élément continu de plaques orthotropes, sandwichs et multicouches. La démarche consiste dans un premier temps à établir la matrice de raideur dynamique de plaques orthotropes pour des conditions aux limites naturelles à partir d’une reformulation des éléments de plaques isotropes développés au laboratoire QUARTZ (EA7393). La démarche est basée d’une part sur la décomposition des conditions aux limites libres décrite par Gorman et d’autre part sur la résolution des équations de mouvement en se basant sur les développements en séries de Levy. La matrice de raideur dynamique est ensuite obtenue par projection des déplacements et des efforts de frontières sur des bases fonctionnelles compatibles avec les opérations d’assemblage. Dans un second temps, la formulation des éléments sandwichs et multicouches est décrite par superposition des plaques orthotropes précédemment développées.Les formulations présentées prennent en compte les vibrations de flexion et les vibrations dans le plan, dites vibrations de membrane. La validation de ces éléments est menée par une confrontation systématique de réponses harmoniques non amorties avec celles obtenues par diverses modélisations éléments finis<br>This thesis deals with the development of a continuous element for orthotropic, sandwich and multilayer plates. This approach is based essentially on the construction of the dynamic stiffness matrix of orthotropic plates using natural boundary conditions from a reformulation of the isotropic plate elements developed in the QUARTZ laboratory (EA 7393). In order to develop the dynamic stiffness matrix of the studied element we resort on the first hand to the decomposition of free boundary conditions described by Gorman, on the second hand to the resolution of the equations of motion by using Levy series expansions. The dynamic stiffness matrix is then obtained by projecting movements and frontier efforts on functional bases compatible with assembly operations. Finally the continuous sandwich and multilayer plate element is described by superposition of continuous orthotropic plates element previously developed.The formulations presented takes into account the bending vibration and the vibration in the plane, called membrane vibration. The validation of all obtained results is conducted by a systematic comparison of undamped harmonic responses with those obtained by various finite element models
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Sugishita, Sotaro. "Construction of a new model generating three-dimensional random volumes:Towards a formulation of membrane theory." 京都大学 (Kyoto University), 2016. http://hdl.handle.net/2433/215308.
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Charton, Christophe. "Matrices expérimentales à usage odontologique : formulation, élaboration, caractérisation et leurs influences sur les contraintes de contraction." Thesis, Vandoeuvre-les-Nancy, INPL, 2009. http://www.theses.fr/2009INPL023N/document.
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Les résines composites à base de polymères diméthacrylates sont des biomatériaux fréquemment employés en dentisterie où la matrice est synthétisée in vivo par photopolymérisation en chaîne radicalaire. En Odontologie Conservatrice, la contraction volumique dont cette matrice est le siège au cours de sa synthèse est un inconvénient majeur. Elle est, en effet, à l’origine de contraintes physiques souvent néfastes et mal contrôlées dès lors que le matériau, collé aux murs cavitaires, est élaboré en milieu confiné. Aucune étude n'a permis à ce jour d’analyser de manière approfondie ce phénomène de contraintes de contraction au regard des conditions opératoires de la synthèse de la matrice. Le but de ce travail est donc d'isoler la problématique des contraintes internes en orientant exclusivement l’étude vers l'analyse de la matrice. En élaborant des prototypes à base de Bis-GMA et d’UEDMA et après caractérisation de certaines propriétés physico-chimiques, rhéologiques et thermodynamiques des mélanges de ces comonomères et des copolymères résultants, ce travail a permis de contribuer à une meilleure compréhension de la phénoménologie de la relaxation viscoélastique qui gouverne la dissipation des contraintes de contraction<br>Composite materials containing polymers are biomaterials frequently employed in dentistry where the matrix is synthesized in vivo by photocured radical chain. In Operative Dentistry, the resulting shrinkage strain produced during the synthesis of this matrix is a major disadvantage. It is, indeed, at the origin of often harmful and badly controlled physical stresses since the material, stuck to the cavity walls, is elaborated in confined surroundings. No study to date allowed analyzing thoroughly this phenomenon of contraction taking into consideration the operating conditions of the synthesis of the matrix. The goal of this work is thus to exclusively isolate the set of problems of the internal stresses by directing the study towards the matrix analysis. By elaborating prototypes based on Bis-GMA and UEDMA and after characterization of certain physicochemical, rheological and thermodynamic properties of mixtures of these comonomers and of the resulting copolymers, this work made it possible to contribute to a better understanding of the phenomenology of the viscoelastic relaxation which governs the dissipation of the shrinkage stress
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Junnarkar, Gunjan Harshad. "Effect of selected adjuvants on metronidazole release from poly(ortho ester) matrix and computer optimization of the formulation." Scholarly Commons, 1995. https://scholarlycommons.pacific.edu/uop_etds/2782.
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In the present study, a 8 x 4 mm biodegradable device was formulated using poly(ortho ester) and metronidazole for treatment of periodontitis. Investigation focussed upon determination of formulation parameters in the form of drug (metronidazole) and adjuvant concentrations (oleic acid and palmitic acid) and device thickness necessary to achieve constant release of 0.6 μg/hr over a period of 7 days and complete degradation of the device over a period of 11 to 13 days. Presence of oleic or palmitic acid influenced the release and erosion profile considerably. Thickness of the device did not have significant influence on the drug release. The DSC and NMR studies indicated absence of interaction between drug and polymer. Computer optimization studies indicate that the optimum formulation for 7 day constant drug delivery and disappearance in 13 days should contain 0.28% w/w of oleic acid and 5.26% w/w of metronidazole at the thickness of 400-450 or 500-550 μm. This is in close agreement with the optimum formulation which was obtained with the experimental data.
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Nino, Ruiz Elias David. "Efficient formulation and implementation of ensemble based methods in data assimilation." Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/64438.
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Ensemble-based methods have gained widespread popularity in the field of data assimilation. An ensemble of model realizations encapsulates information about the error correlations driven by the physics and the dynamics of the numerical model. This information can be used to obtain improved estimates of the state of non-linear dynamical systems such as the atmosphere and/or the ocean. This work develops efficient ensemble-based methods for data assimilation.
A major bottleneck in ensemble Kalman filter (EnKF) implementations is the solution of a linear system at each analysis step. To alleviate it an EnKF implementation based on an iterative Sherman Morrison formula is proposed. The rank deficiency of the ensemble covariance matrix is exploited in order to efficiently compute the analysis increments during the assimilation process. The computational effort of the proposed method is comparable to those of the best EnKF implementations found in the current literature. The stability analysis of the new algorithm is theoretically proven based on the positiveness of the data error covariance matrix.
In order to improve the background error covariance matrices in ensemble-based data assimilation we explore the use of shrinkage covariance matrix estimators from ensembles. The resulting filter has attractive features in terms of both memory usage and computational complexity. Numerical results show that it performs better that traditional EnKF formulations.
In geophysical applications the correlations between errors corresponding to distant model components decreases rapidly with the distance. We propose a new and efficient implementation of the EnKF based on a modified Cholesky decomposition for inverse covariance matrix estimation. This approach exploits the conditional independence of background errors between distant model components with regard to a predefined radius of influence. Consequently, sparse estimators of the inverse background error covariance matrix can be obtained. This implies huge memory savings during the assimilation process under realistic weather forecast scenarios. Rigorous error bounds for the resulting estimator in the context of data assimilation are theoretically proved. The conclusion is that the resulting estimator converges to the true inverse background error covariance matrix when the ensemble size is of the order of the logarithm of the number of model components.
We explore high-performance implementations of the proposed EnKF algorithms. When the observational operator can be locally approximated for different regions of the domain, efficient parallel implementations of the EnKF formulations presented in this dissertation can be obtained. The parallel computation of the analysis increments is performed making use of domain decomposition. Local analysis increments are computed on (possibly) different processors. Once all local analysis increments have been computed they are mapped back onto the global domain to recover the global analysis. Tests performed with an atmospheric general circulation model at a T-63 resolution, and varying the number of processors from 96 to 2,048, reveal that the assimilation time can be decreased multiple fold for all the proposed EnKF formulations.Ensemble-based methods can be used to reformulate strong constraint four dimensional variational data assimilation such as to avoid the construction of adjoint models, which can be complicated for operational models. We propose a trust region approach based on ensembles in which the analysis increments are computed onto the space of an ensemble of snapshots. The quality of the resulting increments in the ensemble space is compared against the gains in the full space. Decisions on whether accept or reject solutions rely on trust region updating formulas. Results based on a atmospheric general circulation model with a T-42 resolution reveal that this methodology can improve the analysis accuracy.<br>Ph. D.
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Chen, Tzu Fu. "Relationship between formulation and noise of phenolic resin matrix friction lining tested in acoustic chamber on automotive brake dynamometer /." Available to subscribers only, 2008. http://proquest.umi.com/pqdweb?did=1674101271&sid=2&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Thesis (M.S.)--Southern Illinois University Carbondale, 2008.<br>"Department of Mechanical Engineering and Energy Processes." Keywords: Automobile brake linings, Brake noise, Brake squeal. Includes bibliographical references (p. 130-135). Also available online.
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Chen, TzuFu. "Relationship Between Formulation and Noise of Phenolic Resin Matrix Friction Lining Tested in Acoustic Chamber on Automotive Brake Dynamometer." OpenSIUC, 2008. https://opensiuc.lib.siu.edu/theses/482.
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The main objective of this research is to address the relationship between formulation of friction lining materials and their propensity to friction induced noise generation. The basic idea was formulated earlier by Dr. Filip, who showed that the friction layer plays the relevant role when noise is observed during braking. It was shown that when newly formed patches (parts of the friction layer) exhibit a large difference in the coefficient of friction, brake lining is stretched and released repeatedly, which leads to significant vibrations and corresponding noise when coupled with the vibration mode of the system. Farhang ,on the other hand, demonstrated that noise can be related to specific surface roughness parameters and when properties of friction lining and friction layer (such as compressibility, stiffness and modulus of elasticity) fit into certain specific value ranges, noisy behavior occurs. This research will address the braking related to friction induced noise in relation to the properties of the bulk lining material and the character and properties of the friction layer. The friction tests will be performed using the CAFS-developed (Szary and Lee) real time noise measurement system compatible with the major part of SAEJ2521 standard (note that the system does not allow for reliable measurement of frequencies lower than 900 Hz). The mechanical properties of fourteen samples will be investigated. Of the fourteen samples, friction layer of three of the samples will be investigated by several analytical techniques developed by Dr. Filip [1]. They include polarized light microscopy, scanning and transmission electron microscopy equipped with energy dispersive microanalysis, and X-ray diffraction. This research summarizes data from the J2521 dynamometer test of the Dodge Caravan samples exhibiting specific compressibility, porosity and hardness. Also, this research provides the results of friction surface analysis by SEM with energy dispersive microanalysis, light microscopy, surface roughness, and X ray diffraction. Of the fourteen samples, Bendix has the largest occurrence of noisy braking. Based on techniques developed by Dr. Filip, the characteristics of the friction layer strongly influence brake noise propensity. The friction layer characteristics are dependent on brake formulation. As predicted, "noisy stop" and "quiet stop" samples exhibit completely different friction surfaces.
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Earnest, Arul. "Addressing issues in sparseness, ecological bias and formulation of the adjacency matrix in Bayesian spatio-temporal analysis of disease counts." Thesis, Queensland University of Technology, 2010. https://eprints.qut.edu.au/31842/1/Arul_Earnest_Thesis.pdf.
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The main objective of this PhD was to further develop Bayesian spatio-temporal models (specifically the Conditional Autoregressive (CAR) class of models), for the analysis of sparse disease outcomes such as birth defects. The motivation for the thesis arose from problems encountered when analyzing a large birth defect registry in New South Wales. The specific components and related research objectives of the thesis were developed from gaps in the literature on current formulations of the CAR model, and health service planning requirements. Data from a large probabilistically-linked database from 1990 to 2004, consisting of fields from two separate registries: the Birth Defect Registry (BDR) and Midwives Data Collection (MDC) were used in the analyses in this thesis.
The main objective was split into smaller goals. The first goal was to determine how the specification of the neighbourhood weight matrix will affect the smoothing properties of the CAR model, and this is the focus of chapter 6. Secondly, I hoped to evaluate the usefulness of incorporating a zero-inflated Poisson (ZIP) component as well as a shared-component model in terms of modeling a sparse outcome, and this is carried out in chapter 7. The third goal was to identify optimal sampling and sample size schemes designed to select individual level data for a hybrid ecological spatial model, and this is done in chapter 8. Finally, I wanted to put together the earlier improvements to the CAR model, and along with demographic projections, provide forecasts for birth defects at the SLA level. Chapter 9 describes how this is done.
For the first objective, I examined a series of neighbourhood weight matrices, and showed how smoothing the relative risk estimates according to similarity by an important covariate (i.e. maternal age) helped improve the model’s ability to recover the underlying risk, as compared to the traditional adjacency (specifically the Queen) method of applying weights.
Next, to address the sparseness and excess zeros commonly encountered in the analysis of rare outcomes such as birth defects, I compared a few models, including an extension of the usual Poisson model to encompass excess zeros in the data. This was achieved via a mixture model, which also encompassed the shared component model to improve on the estimation of sparse counts through borrowing strength across a shared component (e.g. latent risk factor/s) with the referent outcome (caesarean section was used in this example). Using the Deviance Information Criteria (DIC), I showed how the proposed model performed better than the usual models, but only when both outcomes shared a strong spatial correlation.
The next objective involved identifying the optimal sampling and sample size strategy for incorporating individual-level data with areal covariates in a hybrid study design. I performed extensive simulation studies, evaluating thirteen different sampling schemes along with variations in sample size. This was done in the context of an ecological regression model that incorporated spatial correlation in the outcomes, as well as accommodating both individual and areal measures of covariates. Using the Average Mean Squared Error (AMSE), I showed how a simple random sample of 20% of the SLAs, followed by selecting all cases in the SLAs chosen, along with an equal number of controls, provided the lowest AMSE.
The final objective involved combining the improved spatio-temporal CAR model with population (i.e. women) forecasts, to provide 30-year annual estimates of birth defects at the Statistical Local Area (SLA) level in New South Wales, Australia. The projections were illustrated using sixteen different SLAs, representing the various areal measures of socio-economic status and remoteness. A sensitivity analysis of the assumptions used in the projection was also undertaken.
By the end of the thesis, I will show how challenges in the spatial analysis of rare diseases such as birth defects can be addressed, by specifically formulating the neighbourhood weight matrix to smooth according to a key covariate (i.e. maternal age), incorporating a ZIP component to model excess zeros in outcomes and borrowing strength from a referent outcome (i.e. caesarean counts). An efficient strategy to sample individual-level data and sample size considerations for rare disease will also be presented. Finally, projections in birth defect categories at the SLA level will be made.
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Seidenberger, Tanja Verfasser], Karsten [Akademischer Betreuer] [Mäder, Jürgen Akademischer Betreuer] Siepmann, and Reinhard H. H. [Akademischer Betreuer] [Neubert. "Sucrose ester stearates, amphiphilic matrix systems for the formulation of sustained release preparations / Tanja Seidenberger. Betreuer: Karsten Mäder ; Jürgen Siepmann ; Reinhard Neubert." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2011. http://d-nb.info/1025136012/34.
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Zhi, Kaining. "Formulation and Fabrication of a Novel Subcutaneous Implant for the Zero-Order Release of Selected Protein and Small Molecule Drugs." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/482373.
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Pharmaceutical Sciences<br>Ph.D.<br>Diabetes is a leading cause of death and disability in the United States. Diabetes requires a lifetime medical treatment. Some diabetes drugs could be taken orally, while others require daily injection or inhalation to maximize bioavailability and minimize toxicity. Parenteral delivery is a group of delivery routes which bypass human gastrointestinal track. Among all the parenteral methods, we chose subcutaneous implant based on its fast act and high patient compliance. When using subcutaneous implant, drug release needs to be strictly controlled. There are three major groups of controlled release methods. Solvent controlled system is already used as osmotic implant. Matrix controlled system is used in Zoladex® implant to treat cancer. Membrane controlled systems is widely used in coating tablets, but not that popular as an implant. Based on the research reported by previous scientists, we decided to build a hybrid system using both matrix and membrane control to delivery human insulin and other small molecule drugs. Subcutaneous environment is different from human GI track. It has less tolerance for external materials so many polymers cannot be used. From the FDA safe excipient database, we selected albumin as our primary polymer and gelatin as secondary choice. In our preliminary insulin diffusion study, we successfully found that insulin mixed with albumin provided a slower diffusion rate compared with control. In addition, we added zinc chloride, a metal salt that can precipitate albumin. The insulin diffusion rate is further reduced. The preliminary study proved that matrix control using albumin is definitely feasible and we might add zinc chloride as another factor. In order to fabricate an implant with appropriate size, we use lyophilisation technology to produce uniformly mixed matrix. Apart from albumin and human insulin, we added sucrose as protectant and plasticizer. The fine powder after freeze-dry was pressed as a form of tablet. The tablets were sealed in Falcon® cell culture insert. Cell culture insert provide a cylinder shape and 0.3 cm2 surface area for drug release. Insulin release study provided a zero order kinetics from prototypes with zinc chloride or 0.4 micron pore size membrane. Caffeine was used as a model drug to investigate the releasing mechanism. Three pore size membranes (0.4, 3 and 8 micron) were tested with same formulation. While 0.4 micron prototypes provided the slowest release, 3 micron ones surprisingly released caffeine faster than 8 micron implants. We calculated the porosity with pore size and concluded that the percentage of open area on a membrane is the key point to control caffeine release. 0.4 micron membranes were used for future research. We increased the percentage of albumin in our excipient, and achieved a slower caffeine release. However, the zero order release could only last for 3 days. After we replaced sucrose with gelatin, a 5 day zero order release of caffeine was achieved. With all the results, we proposed our “Three Phase” drug release mechanism controlled by both membrane and matrix. Seven other small molecule drugs were tested using our prototype. Cloudy suspension was observed with slightly soluble drugs. We updated our “Three Phase” drug release mechanism with the influence of drug solubility. Data shows that releasing rate with same formulation and membrane follows the solubility in pH 7.4. This result proves that our prototype might be used for different drugs based on their solubility. Finally, with all the information of our prototype, we decided to build a “smart insulin implant” with dose adjustment. We proposed an electrical controlled implant with different porosity membranes. Solenoid was used as the mechanical arm to control membrane porosity. 3-D printing technology was used to produce the first real prototype of our implant. Finally, insulin implant with clinically effective insulin release rate was achieved.<br>Temple University--Theses
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Nguyen, Minh Tuan. "Contribution à la formulation symétrique du couplage équations intégrales - éléments finis : application à la géotechnique." Phd thesis, Université Paris-Est, 2010. http://tel.archives-ouvertes.fr/tel-00607258.
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Un des outils numériques les plus utilisés en ingénierie est la méthode des éléments finis, qui peut être mise en o euvre grâce à l'utilisation de nombreux codes de calcul. Toutefois, une difficulté apparaît lors de l'utilisation de la méthode des éléments finis, spécialement en géotechnique, lorsque la structure étudiée est en interaction avec un domaine de dimensions infinies. L'usage courant en ingénierie est alors de réaliser les calculs sur des domaines bornés, mais la définition de la frontière de tels domaines bornés pose de sérieux problèmes. Pour traiter convenablement les problèmes comportant des frontières à l'infini, l'utilisation d'éléments discrets "infinis" est maintenant souvent délaissée au profit de la méthode des équations intégrales ou "méthode des éléments de frontière" qui permet de résoudre un système d'équations aux dérivées partielles linéaire dans un domaine infini en ne maillant que la frontière du domaine à distance finie. La mise en oeuvre du couplage entre la méthode des éléments finis et la méthode des éléments de frontière apparaît donc comme particulièrement intéressante car elle permet de bénéficier de la flexibilité des codes de calcul par éléments finis tout en permettant de représenter les domaines infinis à l'aide de la méthode des éléments de frontière. La méthode est basée sur la construction de la "matrice de raideur" du domaine infini grâce à l'utilisation de la méthode des équations intégrales. Il suffit alors d'assembler la matrice de raideur du domaine infini avec la matrice de raideur du domaine fini représenté par éléments finis. L'utilisation de la méthode la plus simple de traitement des équations intégrales, dite méthode de " collocation " conduit à une matrice de raideur non-symétrique. Par ailleurs, la méthode dite "Singular Galerkin" conduit à une formulation symétrique, mais au prix du calcul d'intégrales hypersingulières. La thèse porte sur une nouvelle formulation permettant d'obtenir une matrice de raideur symétrique sans intégrales hypersingulières, dans le cas de problèmes plans. Quelques applications numériques sont abordées pour des problèmes courants rencontrés en géotechnique
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Bouchikhi, Aurélie. "Contribution à la formulation d’un béton végétal structurel à base cimentaire incorporant des co-produits / déchets de bois." Thesis, Ecole nationale supérieure Mines-Télécom Lille Douai, 2019. http://www.theses.fr/2019MTLD0009.
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Le bâtiment est un secteur particulièrement émissif en gaz à effet de serre. Pour tenter de réduire l’impact des matériaux sur l’environnement, de nombreuses recherches visent à étudier différentes alternatives pour limiter l’épuisement des ressources, la consommation d’énergie et le rejet de composés polluants. Dans ce contexte, les bétons biosourcés se positionnent comme une alternative sérieuse au béton traditionnel, avec une empreinte carbone plus faible.Cette thèse industrielle, portée par l’entreprise ALKERN, leader en France et en Belgique de produits préfabriqués en béton, a pour objectif de contribuer à la formulation d’un béton végétal incorporant des co-produits / déchets de bois structurel à impact environnemental plus faible que le Naturbloc®, un bloc actuellement sur le marché. Ce dernier produit est constitué de granulats de bois minéralisé puis introduit dans une matrice cimentaire.Ce travail s’articule en trois volets. Les bois témoin (non traité) et de référence (minéralisé) ont d’abord été caractérisés. Dans un second temps, des traitements alternatifs à la minéralisation du bois ont été testés et caractérisés, notamment au regard de leur reprise en eau et leur aptitude à relarguer ou contenir les extractibles présents dans les végétaux. Leur compatibilité avec une matrice cimentaire a également été évaluée. Il a ainsi pu être mis en évidence que la nature du substrat influence les résultats et l’interaction des granulats avec la pâte cimentaire.Enfin, le bois traité a été introduit dans la matrice cimentaire témoin et dans une matrice alternative à plus faible impact environnemental. Cette dernière a été obtenue soit par un changement de liant, soit par une adjuvantation spécifique du béton. L’ensemble des résultats montrent qu’il existe un lien direct entre les propriétés physico-chimiques des granulats et les performances mécaniques obtenues pour le béton<br>The construction industry produces a high amount of greenhouse gases. In order to reduce the impact of materials on the environment, a lot of researches are focused on the study of different alternatives to limit the exhaustion of resources, the energy consumption and the rejection of polluting compounds. In this context, bio-based concrete seem to be a serious alternative to traditional concrete, with a lower carbon footprint.The aim of this industrial thesis, supported by the company ALKERN, leader in France and in Belgium for precast concrete products, is to contribute to the formulation of structural green concrete incorporating co-products / wood waste with an environmental impact lower than the Naturbloc®, a block already available on the market. This last product is made of wood aggregates mineralized and then introduced in a cementitious matrix.This work is divided into three parts. Firstly, the control wood (untreated) and reference wood (mineralized) were characterized. Then, alternative treatments to replace cement coating of wood were tested and characterized, especially in terms of water uptake and ability to leach or hold the extractives present in vegetables back. Their compatibility with a cementitious matrix was also evaluated. The study highlights the fact that the nature of the substrate has an influence on the results and on the interaction between aggregates and cementitious paste.Finally, treated wood was introduced into a cementitious matrix and in an alternative matrix with a lower environmental impact. The latter was obtained either by change of the binder or by use of additives in bio-based concrete. All the results show the existence of a direct link between physico-chemical properties of aggregates and mechanical performances of concrete
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Jara-Almonte, J. "Extraction of eigen-pairs from beam structures using an exact element based on a continuum formulation and the finite element method." Diss., Virginia Polytechnic Institute and State University, 1985. http://hdl.handle.net/10919/54300.
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Studies of numerical methods to decouple structure and fluid interaction have reported the need for more precise approximations of higher structure eigenvalues and eigenvectors than are currently available from standard finite elements. The purpose of this study is to investigate hybrid finite element models composed of standard finite elements and exact-elements for the prediction of higher structure eigenvalues and eigenvectors.
An exact beam-element dynamic-stiffness formulation is presented for a plane Timoshenko beam with rotatory inertia. This formulation is based on a converted continuum transfer matrix and is incorporated into a typical finite element program for eigenvalue/vector problems. Hybrid models using the exact-beam element generate transcendental, nonlinear eigenvalue problems. An eigenvalue extraction technique for this problem is also implemented. Also presented is a post-processing capability to reconstruct the mode shape each of exact element at as many discrete locations along the element as desired.
The resulting code has advantages over both the standard transfer matrix method and the standard finite element method. The advantage over the transfer matrix method is that complicated structures may be modeled with the converted continuum transfer matrix without having to use branching techniques. The advantage over the finite element method is that fewer degrees of freedom are necessary to obtain good approximations for the higher eigenvalues. The reduction is achieved because the incorporation of an exact-beam-element is tantamount to the dynamic condensation of an infinity of degrees of freedom.
Numerical examples are used to illustrate the advantages of this method. First, the eigenvalues of a fixed-fixed beam are found with purely finite element models, purely exact-element models, and a closed-form solution. Comparisons show that purely exact-element models give, for all practical purposes, the same eigenvalues as a closed-form solution. Next, a Portal Arch and a Verdeel Truss structure are modeled with hybrid models, purely finite element, and purely exact-element models. The hybrid models do provide precise higher eigenvalues with fewer degrees of freedom than the purely finite element models. The purely exact-element models were the most economical for obtaining higher structure eigenvalues. The hybrid models were more costly than the purely exact-element models, but not as costly as the purely finite element models.<br>Ph. D.
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Webb, Kerri. "Matrix Formulations of Matching Problems." Thesis, University of Waterloo, 2000. http://hdl.handle.net/10012/1119.
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Finding the maximum size of a matching in an undirected graph and finding the maximum size of branching in a directed graph can be formulated as matrix rank problems. The Tutte matrix, introduced by Tutte as a representation of an undirected graph, has rank equal to the maximum number of vertices covered by a matching in the associated graph. The branching matrix, a representation of a directed graph, has rank equal to the maximum number of vertices covered by a branching in the associated graph. A mixed graph has both undirected and directed edges, and the matching forest problem for mixed graphs, introduced by Giles, is a generalization of the matching problem and the branching problem. A mixed graph can be represented by the matching forest matrix, and the rank of the matching forest matrix is related to the size of a matching forest in the associated mixed graph. The Tutte matrix and the branching matrix have indeterminate entries, and we describe algorithms that evaluate the indeterminates as rationals in such a way that the rank of the evaluated matrix is equal to the rank of the indeterminate matrix. Matroids in the context of graphs are discussed, and matroid formulations for the matching, branching, and matching forest problems are given.
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Gunduz, Aydin. "Multi-Dimensional Stiffness Characteristics of Double Row Angular Contact Ball Bearings and Their Role in Influencing Vibration Modes." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1326397623.
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Cousinet, Sylvain. "Evaluation de nouvelles matrices organiques biosourcées sans styrène pour composites SMC." Thesis, Lyon, INSA, 2013. http://www.theses.fr/2013ISAL0149.
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De par leurs bonnes propriétés mécaniques, leur faible densité, leur faible coût, et leur bel aspect de surface, les composites SMC (Sheet Molding Compound) sont des matériaux de choix pour réaliser des pièces automobiles semi-structurelles. Ces matériaux sont principalement constitués d’une résine polyester (UPR), d’un additif thermoplastique comme agent anti-retrait, de carbonate de calcium comme charge et de fibres de verre coupées comme renfort. Le contexte environnemental et socio-économique actuel encourage les constructeurs automobiles à utiliser des matériaux issus de ressources renouvelables afin de réduire l’utilisation des réserves pétrolières, et de trouver une alternative au styrène (COV, polluant atmosphérique dangereux et potentiellement cancérigène) qui est utilisé comme diluant réactif (DR) dans les UPR. L’objectif de ce travail est de développer une matrice organique biosourcée (UPR et agent anti-retrait) pour composite SMC moulable par le même procédé de mise en forme et présentant le même niveau de performance comparé à l’existant pétrosourcé. La première partie de ce travail est consacrée à l’évaluation de nouveaux diluants réactifs biosourcés (MMA, BDDMA, BDDVE, EDI, IBOMA et LMA) comme substituants du styrène sur la base des contraintes liées au procédé SMC. Les résines sélectionnées ont ensuite été polymérisées et les réseaux obtenus caractérisés. Le mécanisme de copolymérisation a été étudié et a permis de mettre en évidence l’influence de la nature chimique des insaturations et de la fonctionnalité du DR sur les propriétés finales du réseau. De par sa faible viscosité, sa faible volatilité et son point éclair élevé, le BDDMA est un bon candidat pour remplacer le styrène dans les UPR. La partie suivante est consacrée à la caractérisation d’un prépolymère polyester insaturé et de différents agents anti-retrait biosourcés. Des matrices organiques ont été formulées avec différents agents anti-retrait, puis polymérisées et caractérisées. L’influence de la nature et du taux d’agent anti-retrait sur le retrait de polymérisation et les propriétés mécaniques a été évaluée. Des essais sur composites SMC à l’échelle pilote ont été réalisés afin d’étudier les propriétés finales des composites biosourcés. La meilleure compensation du retrait est obtenue pour l’additif de plus faible Tg, c'est-à-dire le polyester saturé biosourcé. Le réseau à base de BDDMA étant très fragile, la suite de ce travail a consisté à réduire la densité de réticulation du réseau en introduisant un monométhacrylate biosourcé dans la formulation (MMA, IBOMA et LMA) afin d’améliorer les propriétés au choc du matériau. Enfin, un nouveau DR biosourcé, le lévulinate de vinyle, a été évalué comme substituant du styrène dans les UPR. Le mécanisme de copolymérisation a été mis en évidence et relié à la structure et aux propriétés finales du réseau<br>Due to their good mechanical properties, low density, low cost and good surface properties, SMC composites (Sheet Molding Compound) are suitable for manufacturing half-structural automotive parts. These materials are mainly based on a unsaturated polyester resin (UPR), thermoplastics as low profile additives, calcium carbonate as filler and chopped glass fibers. Current environmental and socio-economic concerns motivate automotive manufacturers to use bio-based materials in order to reduce the use of crude oil reserves and to find an alternative to styrene (VOC, hazardous air pollutant, potential carcinogen) which is used as reactive diluents (RD) in UPR. The aim of this work was to develop a bio-based organic matrix (UPR and low profile additive) for SMC composites with a similar processability and same level of performances compared to petroleum-based analogs. The first part of this work describes the evaluation of new bio-based reactive diluents (MMA, BDDMA, BDDVE, EDI, IBOMA and LMA) as styrene substituents for UPR, taking into account SMC process requirements. Selected resins were polymerized and the obtained networks characterized. Copolymerization mechanism was studied and allowed to highlight the influence of the chemical nature of unsaturations and the functionality of reactive diluents on network properties. Due to its low viscosity, low volatility and high flashpoint, BDDMA is a good candidate to replace styrene in UPR. Next part was dedicated to the characterization of bio-based unsaturated polyester and low profile additives. Several organic matrices were formulated with different low profile additives, then polymerized and characterized. The influence of the low profile additive nature and content on the polymerization shrinkage and mechanical properties of the material was evaluated. SMC composites were manufactured at the pilot scale and characterized in order to study the final properties of bio-based composites. The best shrinkage control is obtained with low-Tg additive (bio-based saturated polyester). Nevertheless BDDMA-based network is very brittle, so a next step of our work was to introduce a monofunctional methacrylate (MMA, IBOMA and LMA) into the matrix in order to decrease the crosslink density of the network and improve its impact resistance. The influence of the methacrylate nature and content on the structure and mechanical properties of the polyester networks was highlighted. Finally, a new bio-based RD, vinyl levulinate, was evaluated to replace styrene in UPR. Its copolymerization mechanism with UP was studied and related to the structure and mechanical properties of the network
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Lee, Jobina J. N. "Investigations into sustained-release hydrophobic matrix pellet formulations." Thesis, University of Strathclyde, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275167.
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El, fakhri Rehab M. Mohamed. "Cryomilling for formulation." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/49060/.
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The pharmaceutical industry has experienced an increase in the amount of development candidates with low aqueous solubility and accordingly poor bioavailability. In order for this problem to be solved, amorphisation is thought to be the most favourable solution. The amorphous state is higher in free energy thus higher in solubility when compared to the crystalline form. Milling and specially cryomilling is a very unique technique for providing of the crystalline to amorphous transformation since there are no heat or solvents involved. Phthalic acid, isophthalic acid and terephthalic acid, individual and pair mixtures, are crystalline organic non medicinal compounds, which have been used for the first time as model compounds to investigate whether cryogenic milling can induce crystal to amorphous transformation and if the preparation of pair mixtures could affect the recrystallization rate of the subjected materials or not. The materials were cryomilled and analysed by DSC, XRPD, and FTIR. It was found that only terephthalic acid become amorphous after cryomilling, and even after the cryomilled sample been stored for three weeks DSC thermogram still detects recrystallization exothermic along with the XRPD pattern, which shows a very broad peaks indicative of particle size reduction. Pair mixtures were also studied and analysed by DSC and XRPD. Phthalic acid/isophthalic acid, isophthalic acid/terephthalic acid, phthalic acid/terephthalic acid were cryomilled together and mixed physically after been cryomilled separately. XRPD results show that unlike the cryomilled separately mixtures, phthalic acid/ isophthalic acid, isophthalic acid/terephthalic acid, terephthalic acid/phthalic acid cryomilled together samples produces a synergistic effect in which the Bragg peaks of both phthalic acid and isophthalic acid are suppressed. It appears that co cryomilling of these pair mixtures together resulted in the production of a new material that could potentially either be two-component single phase (nano-sized co-crystal), or a new polymorphic form of either phthalic acid, isophthalic acid or terephthalic acid. Single-component of aspirin (ASP), paracetamol (PCM) and caffeine (CAFF), along with multi-component systems of paracetamol/aspirin, paracetamol/caffeine and aspirin/caffeine were milled at room temperature and by a cryomill. The milled samples were analysed using DSC, XRPD and FTIR. It was noted that there are no clear indications of crystal to amorphous transformation in all three materials. When milling aspirin at room temperature a marked reduction in the melting point was observed. Generally, a reduction in the melting point is either attributed to particle size effects, polymorphism, impurities and decomposition. In this case, the decrease in the melting point was only noticed when aspirin was milled at room temperature, so it is possible that the heat generated during the milling process resulted in chemical decomposition of aspirin to salicylic acid. Anhydrous caffeine is acknowledged to have two polymorphic forms, Form II which is considered to be stable at room temperature until ~145 °C. Form I is stable from ~145 °C to its melting point ~ 236 °C. This polymorphic transformation was detected by DSC, XRPD and hot stage microscope and it was noticed only with the as received and the room temperature milled samples. Cryomilled caffeine data showed only the presence of Form I. On the other hand, for the cryomilled multi-component systems DSC and hot stage microscope images confirmed the eutectic formation with a composition of 45:55% w/w (PCM:ASP), 50:50% (ASP:CAFF) AND 50:50% (PCM:CAFF). The obtained data were compared with room temperature milled and the theoretical values resulted from Van Laar equation. Solid pharmaceuticals represent heterogeneous systems that typically consist of one or more active pharmaceutical ingredients (APIs) and a number of excipients. Multi-component systems from mixing aspirin, paracetamol and caffeine with different excipients, which included sucrose, lactose monohydrate, xylitol and trehalose dihydrate were prepared by the use of a cryomill and were analyesd by DSC and XRPD. It was found from the XRPD data that mixing both sucrose and lactose monohydrate respectively with ASP, PCM and CAFF would produce more of a synergistic effect than xylitol and trehalose dihydrate. Cryomilling caffeine/sucrose and caffeine/lactose resulted in a production of a new XRPD trace that cannot be described in terms of a linear combination of caffeine, sucrose and lactose monohydrate. A new material was therefore formed as a result of cryomilling which has not been reported before.
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Wilkerson, Owen Tanner. "Fast, Sparse Matrix Factorization and Matrix Algebra via Random Sampling for Integral Equation Formulations in Electromagnetics." UKnowledge, 2019. https://uknowledge.uky.edu/ece_etds/147.
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Many systems designed by electrical & computer engineers rely on electromagnetic (EM) signals to transmit, receive, and extract either information or energy. In many cases, these systems are large and complex. Their accurate, cost-effective design requires high-fidelity computer modeling of the underlying EM field/material interaction problem in order to find a design with acceptable system performance. This modeling is accomplished by projecting the governing Maxwell equations onto finite dimensional subspaces, which results in a large matrix equation representation (Zx = b) of the EM problem. In the case of integral equation-based formulations of EM problems, the M-by-N system matrix, Z, is generally dense. For this reason, when treating large problems, it is necessary to use compression methods to store and manipulate Z. One such sparse representation is provided by so-called H^2 matrices. At low-to-moderate frequencies, H^2 matrices provide a controllably accurate data-sparse representation of Z.
The scale at which problems in EM are considered ``large'' is continuously being redefined to be larger. This growth of problem scale is not only happening in EM, but respectively across all other sub-fields of computational science as well. The pursuit of increasingly large problems is unwavering in all these sub-fields, and this drive has long outpaced the rate of advancements in processing and storage capabilities in computing. This has caused computational science communities to now face the computational limitations of standard linear algebraic methods that have been relied upon for decades to run quickly and efficiently on modern computing hardware. This common set of algorithms can only produce reliable results quickly and efficiently for small to mid-sized matrices that fit into the memory of the host computer. Therefore, the drive to pursue larger problems has even began to outpace the reasonable capabilities of these common numerical algorithms; the deterministic numerical linear algebra algorithms that have gotten matrix computation this far have proven to be inadequate for many problems of current interest. This has computational science communities focusing on improvements in their mathematical and software approaches in order to push further advancement. Randomized numerical linear algebra (RandNLA) is an emerging area that both academia and industry believe to be strong candidates to assist in overcoming the limitations faced when solving massive and computationally expensive problems.
This thesis presents results of recent work that uses a random sampling method (RSM) to implement algebraic operations involving multiple H^2 matrices. Significantly, this work is done in a manner that is non-invasive to an existing H^2 code base for filling and factoring H^2 matrices. The work presented thus expands the existing code's capabilities with minimal impact on existing (and well-tested) applications. In addition to this work with randomized H^2 algebra, improvements in sparse factorization methods for the compressed H^2 data structure will also be presented. The reported developments in filling and factoring H^2 data structures assist in, and allow for, the further pursuit of large and complex problems in computational EM (CEM) within simulation code bases that utilize the H^2 data structure.
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Lazzari, Alessia [Verfasser]. "Development of alcohol-resistant single- and multiple-unit matrix formulations / Alessia Lazzari." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1180023528/34.
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Phajongwiriyathorn, Wipapan. "Investigations of the physicochemical properties of waxes and wax matrix pellet formulations." Thesis, University of Strathclyde, 2008. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=21935.
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The research resulted in the development of wax matrix pellet systems using a direct warm spheronisation method for use as sustained release devices in oral drug delivery. The effect of altering process parameters on resultant pellet morphology, size distribution and in vitro dissolution performance was evaluated. Changes in the physicochemical and morphological properties of glyceryl monostearate (GMS) and glyceryl palmitostearate (GPS) used in pellet formulations following ageing were monitored by use of FT-IR spectrophotometry, differential scanning calorimetry, hot stage microscopy, X-ray powder diffraction, texture analyses, polarised light microscopy, scanning electron microscopy and dissolution testing. Use of the direct warm spheronisation process resulted in the production of the unstable α-form of GMS that slowly reverted to the stable β-polymorph upon storage at 25°C but GPS exhibited changes in crystallinity upon storage. Thermal annealing of GMS and GPS formulations at 46°C resulted in the melt-solidified GMS (α-form) more rapidly transforming to the stable β-form whereas melt-solidified GPS crystallised faster when compared to 25°C. The thermal annealing cycle at 46°C caused divergent effects in GMS and GPS pellet formulation dissolution performance with decreased drug release rates observed for GMS pellet formulations and increased drug release rates observed for GPS pellet formulations. Moreover, dissolution performance of pellet formulations after annealing was dependent on both wax and drug composition. The inclusions of excipients that stabilised the thermal properties of wax were only effective in preventing modification in pellet dissolution performance for short periods (2 weeks) post-annealing. The combined use of excipients and thermal annealing to stabilise the properties of waxes and provide consistent performance of the delivery device requires further optimisation before it can be a truly useful application for the industrial manufacture of pharmaceutical wax-based oral delivery devices.
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Zhao, Jing. "The controlled release of herbicides from matrix formulations based on biodegradable polymers." Thesis, University of Newcastle Upon Tyne, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323661.
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Ahmed, Elizabeth Hannah. "Supercritical fluid technology for gastroretentive formulations." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/27853/.
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The oral route for drug administration offers an efficient and convenient method for drug delivery. However, there is an assortment of drugs which exhibit narrow absorption windows in the upper small intestine and as a result demonstrate limited bioavailabilities. One approach in the improvement of bioavailability in these cases is to retain the delivery system proximal to the absorption window for a prolonged period of time. Although controlled release products are widely available on the market, marketed gastroretentive systems remain elusive. This work explores the manufacture and characterisation of a multi-unit gastroretentive system utilising the biocompatible polymer poly (lactic-coglycolic acid). The novel PGSS technique enables the production of PLGA particles whilst omitting the use of volatile organic solvents. Morphological and microCT analyses of the particles revealed a highly porous matrix with porosity values in the order of 30-40%. The relationship between porosity, density and in vitro floating ability for particles with sizes between 100-2000 J.1m revealed that particle size plays an important role; larger microparticles possess decreased density, higher porosity and increased buoyancy. Encapsulation of two model drugs, riboflavin and furosemide, was carried out during the processing step with high encapsulation efficiencies (80-100%) being revealed. Release of the drugs in PBS (pH7.4) was found to be sustained over a period of 24 hours with a decrease in cumulative release in simulated gastric fluid (pHl.2). The introduction of the hydrophilic polymer poly(ethylene glycol) was found to modulate release rate; PEG with a molecular weight equal of more than 3 KDa increased the rate of release in PBS media up to 20% over hrs, however this was not observed for release in SGF. A comparison of morphology prior to and following exposure to the release media confirms that the emergence of intricate porous channels on exposure to the release medium is related to an increase in release rate. In order to augment the gastroretentive potential of the system the mucoadhesive polymer, chitosan was incorporated both as a post processing surface modification and as part of the initial formulation. ToF-SIMS surface analysis confirmed the presence of chitosan at the surface of the particles in both cases. Initially the potential for the particles to interact with mucus was evaluated utilising in vitro tests. The presence of chitosan significantly improved adsorption of mucin to particles, as well as enhancing adhesion of particles to a mucus producing epithelial cell layer. The thiolated chitosan derivative chitosan-N-acetyl-cysteine demonstrated an increase in adhesion of mucin solution; however the modified chitosan resulted in a decrease in adhesion to mucus producing cell line which was considered to be a result of the mucolytic actions it may exert on the mucus layer. Oral administration of buoyant particles to a rat model improved the pharmacokinetics of the anti-hypoglycaemia drug metformin, with addition of mucoadhesive properties providing further improvement. This study demonstrates that introduction of buoyancy and mucoadhesion functionalities to particles prepared by the PGSS method could improve delivery of drugs demonstrating narrow absorption windows in the upper small intestine.
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Beech, Karen E. "Processing and formulation insights for designing quality into lyophilised biopharmaceuticals." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/33176/.
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This thesis makes an original contribution to the field of formulation development by providing new experimental data and insights into the effect of processing and formulation conditions on the quality of lyophilised biopharmaceuticals. The quality attributes of lyophilised products include: a quick reconstitution time, product elegance and protein stability, which are known to be affected by processing and formulation parameters. However, choice of formulation excipients or processing conditions often relies on previous experience rather than mechanistic insight. The motivation of this thesis was therefore to provide a greater understanding of how process variables andexcipient choice affect these quality attributes. Bovine serum albumin (BSA) and immunoglobulin G (IgG) were used as model proteins to investigate formulation conditions, which included the excipient, the lyophilisation cooling profile and duration of the annealing step. BSA was also used as a model protein to explore the effects of sucrose and arginine as lyoprotectants. Unique to this study was the investigation of arginine salts as lyoprotectants, wherein the counterions were dicarboxylic acids with increasing chain length. Two key results regarding quality attributes were observed. Firstly, characterisation of the lyophilised structure established that there was an optimal annealing time, beyond which there was an increase in primary drying time, batch heterogeneity and variable moisture content. Secondly, a relationship was found between decreasing dicarboxylic acid chain length and improved protein stability. To explain these findings, two mechanisms are proposed that account for ice crystal growth during annealing and the observed changes in protein stability at the molecular level. Significantly, this research provides insights for future formulation development studies.
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Thong, Li Ming. "Effect of formulation variables on insulin localisation within solid lipid nanoparticles." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/31206/.
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There has been a lot of interest on solid lipid nanoparticles (SLNs) as these colloidal submicron drug dosage forms present a promising frontier in drug delivery. It is possible to incorporate susceptible drugs such as protein intended for oral delivery. Here, we aim to develop an oral delivery system based on SLNs to deliver the peptide hormone, insulin using the double emulsion (W/O/W) solvent evaporation technique for formulating the SLNs. The choice of lipids was carefully selected to incorporate acceptability to biological milieu. The main purpose of the work was to formulate SLNs to achieve different localisation of insulin within the SLNs, based on the three hypothetical models proposed by Muller et al. (2000). Following that, the effect of this localisation on the propensity of the SLNs to be taken up by absorptive cells was investigated. SLNs was successfully fabricated to achieve two insulin localisation models, namely the solid solution model and the core-shell model with drug-enriched shell. The zeta potential measurements was used to indirectly indicate the appropriate insulin localisation model. The zeta potential of the unloaded SLNs, insulin-loaded SLNs and surface-adsorbed insulin SLNs were recorded as -51.7 ± 1 mV, -45.8 ± 1 mV and -40.8 ± 1 mV respectively. In vitro cell studies showed a notable difference in the Caco-2 cell lines when the cells were exposed to SLNs of the two different insulin localisation models. Thus, different effects seen on the Caco-2 cells suggests that the localisation of insulin within SLNs can potentially influence its uptake, stressing the importance of characterising drug localisation in nanoparticles, as this eventually affects drug bioavailability.
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Divry, Véronique. "Mécanismes de formation et relations structure/propriétés de films minces à matrice polymère issus de colloïdes aqueux à séchage rapide." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAE001/document.
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Les formulations des peintures à l’eau sont basées sur l’utilisation de suspensions colloïdales de particules de polymère dans l’eau (latex) et d’additifs dont principalement des pigments et des charges. La formation d’un film mince à matrice polymère par séchage d’un système colloïdal aqueux donne lieu à des phénomènes interdépendants d’une extrême complexité. Dans le cadre d’applications spécifiques, tels que le marquage routier, le séchage d’un latex formulé nécessite une minimisation des temps de séchage sans apport excessif d’énergie. Néanmoins, une fois sec, le film doit être aussi peu poreux que possible et avoir la meilleur tenue mécanique possible. L’objectif principal de cette thèse était d’identifier les paramètres clés pouvant jouer sur la vitesse de séchage d’une peinture aqueuse et de comprendre comment ces paramètres influencent les propriétés rhéologiques, les mécanismes de séchage du latex formulé et les propriétés mécaniques des films de polymères secs. Ceci dans le but d’apporter une meilleure compréhension au séchage de latex formulés ainsi qu’une aide à la formulation.Après identification des paramètres clés, des latex ont été synthétisés et formulés avec des additifs judicieusement choisis. L'influence des paramètres clés : nature du polymère, taille et distribution en taille des particules, ajout d'un agent de coalescence, d'un co-solvant, d'un agent dispersant et épaississant, de pigments et d’un agent de réticulation, a été étudiée au niveau du séchage des formulations et au niveau des propriétés mécaniques des films secs. Les études sur le séchage ont porté sur le séchage global, les mécanismes de déformation des particules et les mécanismes de séchage horizontal et vertical présent dans les latex. La vitesse de convection horizontale des particules a été mesurée par diffusion multiple de la lumière. Des comparaisons avec des modèles théoriques ont été effectuées. Les propriétés des films secs ont été comparées par analyse dynamique mécanique et par tribologie<br>Aqueous paints are made of colloidal suspensions of polymer in water (latex) and additives (mainly pigments and fillers). Latex film formation consists of complex and interdependent phenomena. In case of specific applications, such as road marking, formulated latex must dry fast without excessive supply of energy. However, once dry, the film must be as less porous as possible, with good mechanical properties. The aim of this thesis was to identify the drying key parameters and to understand their influence on the rheology, the drying mechanisms of formulated latex and the mechanical properties of the dried films. The final goal was to have a better understanding of formulated latex drying in order to improve the formulations. After identification of the drying key parameters, latexes have been synthetized and formulated with specific additives. The influence of the following drying key parameters: nature of polymer, size and size distribution of particles, addition of coalescing aid, co-solvent, dispersing and thickening agent, pigments and cross linker, was studied regarding the formulation drying and the dried films mechanical properties. The drying studies focused on the global drying rate of the formulations, the particles deformation mechanisms and the horizontal and vertical drying mechanisms observed in latexes. The particles horizontal convection rate has been measured with multiple light scattering. Comparisons have been made with theoretical models. Dried films mechanical properties have been compared with dynamic mechanical analysis and tribology
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Scoutaris, Nikolaos. "Home based formulation of personalised medicines by means of inkjet printing technique." Thesis, University of Nottingham, 2011. http://eprints.nottingham.ac.uk/13381/.
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The potential application of inkjet printing technology to produce precisely dosage care is demonstrated in this thesis. Inkjet printing technology as it offers the opportunity to deliver quantities with high accuracy can produce medicines tailored for each patient. The viability of this method was first demonstrated by using Felodipine as an active pharmaceutical ingredient polyvinyl pirrolidone (PVP) as an excipient. Felodipine is an antihypertensive drug which is poorly soluble in water and PVP is a highly soluble polymer commonly used to improve drugs' bioavailability. These were dissolved at various ratios in a mixture of ethanol and DMSO (95/5). Using a piezoelectric driven dispenser, picolitre size droplets of the solutions were dispensed onto suitable hydrophobic substrates. The dried products were characterized using AFM, localized nano-thermal analysis and high resolution vibrational spectroscopy (ATR-IR and Raman). Results indicate intimate mixing of the micro-dot API and excipient mixtures. Specifically, ATR-IR confirmed the interaction of felodipine and PVP by means of hydrogen bonding. Nanothermal analysis indicates a single glass transition point which is lowered as the API concentration increases. Finally, confocal Raman microscopy mapping on single droplets allows the visualization of the homogeneous distribution of the drug. Also, capozide has been used as a model therapeutic system which could be produced rapidly as a viable formulation using the inkjet printing technology. Capozide consists of captopril, an angiotensin converting enzyme (ACE) inhibitor and hydrochlorothiazide, a thiazide diuretic drug, in varying ratios. These active pharmaceutical ingredients (APIs) and poly(lactic-co-glycolic acid) (PLGA) were dissolved in appropriate solvents and using a piezoelectric driven dispenser and pipetting, picolitre and microlitre size droplets respectively were deposited onto hydrophobic coated glass slides. Captopril and PLGA were dissolved in chloroform, ethanol and DMSO (75/18/7). Hydrochlorothiazide (HCT) and PLGA were dissolved in acetone and DMSO (93/7). The dried products where characterised using AFM and high resolution Raman microscopy. The results showed that both capropril and HCT are phase separated with the PLGA. Also, the dissolution profiles of the final products were measured using HPLC where it has been shown that PLGA can control the release of the drug from the formulation. These results are a promising first step to produce pharmaceutical by means of inkjet printing.
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Hussain, Talib. "The application of microwave formulation and isothermal titration calorimetry for pharmaceutical compounds." Thesis, University of Huddersfield, 2014. http://eprints.hud.ac.uk/id/eprint/23397/.
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Solid dispersions are commonly used to overcome bioavailability issues of poorly water soluble drugs. Various preparation methods along with carrier systems have been used to develop solid dispersions. However, this study investigates the application of microwave heating methods in formulation development alongside associated analytical investigations. Formulations of poorly soluble drugs, namely, fenofibrate, gemfibrozil, ibuprofen, ibuprofen (+) S and phenylbutazone were prepared using a microwave technique and compared with standard formulation techniques. Mesoporous silicas and polyethylene glycol were used as excipients. Then in vitro dissolution analysis was carried out for the performance evaluation of the resultant formulations. It was found that effective products were produced as a result of microwave processing compared with the traditional techniques. Analytical techniques such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were employed to determine the solid state properties, i.e. thermal stability, crystalline state, physical appearance and chemical stability of developed formulations. The overall findings indicate that successful formulation can be achieved using microwave heating. Isothermal titration calorimetry (ITC) was used to probe the interactions of model drugs, namely, caffeine, diprophylline, etofylline, paracetamol and theophylline with excipients such as sodium dodecyl sulphate (SDS), sodium deoxycholate (NaDC) and PEG. Thermodynamic data suggests the successful use of ITC to investigate drug-excipient interactions. In summary, the potential of microwave heating in formulation development and ITC to characterise drug-excipient interactions was thoroughly investigated and both found as potential alternatives to more traditional techniques.
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Puri, Sanyogitta. "Novel functionalized polymers for nanoparticle formulations with anti cancer drugs." Thesis, University of Nottingham, 2007. http://eprints.nottingham.ac.uk/10316/.
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The chemistry and structure of Poly (glycerol adipate) facilitate its substitution with various pendant functional groups leading to modifications of the physicochemical properties of the polymer. Modified backbones then can be selected based upon the properties of the compound to be incorporated. Thus, this could be explored as a drug delivery system without many of the limitations of commercially available polymers. The aim of this study was investigate whether various polymers and drugs interact in a specific manner and whether the nature of these interactions influence the physicochemical characteristics of the particles and their drug loading and release profile. By investigating drugs belonging to various classes and with different properties it has been possible to correlate properties associated with drugs and pendant functional groups of the polymer which are ultimately responsible for the drug loading and release characteristics. For some drug polymer formulations, good loading and controlled release rates have been achieved. Compared to various conventional polymer systems reported for nanoparticle formulations, poly (glycerol adipate) polymers have also demonstrated the ability to control rate of release of highly water soluble drugs, even from the most hydrophilic polymer backbone in its unsubstituted form. From the various drug loading and release profiles it has been demonstrated that, unlike reported literature, particle size is not the primary factor influencing drug release over the relatively small range of particle sizes seen in this study. Neither is the water solubility of either the drug or the polymer alone responsible for the rapid and uncontrolled release profile from nanoparticles. Thus, Drug polymer interactions are more likely to influence drug loading and release and unlike common reports in the literature, hydrophilicity, molecular weight or concentration of polymer / drug are less likely to affect these parameters in isolation.
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Khan, Sajjad. "Formulation and characterisation of novel films for buccal mucosa drug delivery for paediatric patients." Thesis, University of Greenwich, 2015. http://gala.gre.ac.uk/14229/.
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The main aim of this project was to develop, formulate, characterise and optimise novel pre-formed thin polymer film that will deliver therapeutically relevant drugs via the buccal mucosa route of paediatric patients, using OME as model drug. The development focused on obtaining formulations with optimized drug loading, drug release and permeation, stability and low toxicity. Five different film forming polymers hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) were used initially and subsequently with polyethylene glycol (PEG 400) as plasticiser and L-arg (to stabilise OME). Polymeric gels (1% w/w) were prepared using water and ethanol (10% v/v and 20% v/v) as the casting solvents with PEG 400 at different concentrations (0 and 0.5 % w/w) and the films were obtained by drying the gels in an oven (40 °C). SA and MET films were chosen for drug loading and further investigation (OME stabilisation). These films showed a good balance between flexibility and toughness required for ease of transportation and patient handling. Drug loaded gels showed that OME was unstable, with gels turning red after 20 minutes and therefore required addition of L-arg. From the results obtained, plasticised (0.5 % w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME : L-arg ratio of 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was the formulation of choice for further investigation. Results obtained for the hydration and in vitro mucoadhesion studies showed that plasticised films had higher swelling capacity and mucoadhesivity than unplasticised films. In addition, BLK films showed higher swelling index and adhesion than DL films, whilst gelatine equilibrated with PBS showed higher values compared with simulated saliva (SS). Dissolution data from optimised DL MET films showed OME release was sustained over 1 hour. Fitting the release data to kinetic models showed that the Korsmeyer-Peppas equations best fit the dissolution data for both PBS and SS media. The permeability profile of optimised DL film using pig buccal tissue, showed that the amount of OME permeating over 2 hours was 275ug/cm2 suggesting that pig buccal membrane is generally quite permeable and also that the OME is released from the films. Application of SCF caused significant changes to the functional and physical properties of the MET films and converted the original DL MET films from a sustained release formulation (1 hour) to a rapid release system, releasing > 90% of OME within 15 minutes and the release of OME from these films followed Higuchi kinetic model. Finally, incorporation of β cyclodextrin (βCD) into DL MET films containing OME:L-arg 1:1, improved the stability of the drug over 28 days under ambient conditions compared to 14 days for the corresponding DL MET films containing only L-arg at a higher loading (OME: L-arg 1:2). The optimised formulations have potential as paediatric buccal delivery system for OME.
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Jin, Zheng. "The micro and nano scale characterization and identification of tablet formulations." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/11073/.
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The aim of this project was to characterize the surface properties of materials used in tablet formulations with sub-micron resolution by the techniques of Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), Scanning Thermal Microscopy (SThM), Nano-TA system, Differential Scanning Calorimeter (DSC), Attenuated Total Reflectance Infrared (ATR-IR), Near-Infrared Spectroscopy (NIR) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). In particular, the work aimed to develop new AFM based methodologies to advance this method both in terms of quantification and mapping. AFM was employed to investigate properties of solid materials such as surface free energy, Young’s modulus, melting point and phase transition temperatures from pharmaceutical materials in blend mixtures with the nanoscale resolution. These approaches developed here provide new tools to understand the process induced changes and stability issues in solid dosage forms such as tablets and inhalation formulations from minute amounts of materials. The surface free energy values of solid materials obtained from AFM adhesion force measurements were described in Chapter 3. The adhesion forces obtained with AFM in low relative humidity environments were used to derive the surface free energy values using the Hertzian and JKR based models. The surface free energy was proposed to be close to the so called dispersion surface free energy since the adhesion forces at low relative humidity mainly resulted from van der Waals forces in the systems studied here. The comparison of surface free energy between AFM and those derived from a contact angle method showed that the dispersion surface free energy values derived from the contact angle method were generally higher than those from AFM. For example, the surface free energy value derived from AFM adhesion force measurements for lactose monohydrate was 33.0 mJ/m2, while from contact angle method the value was 46.8 mJ/m2. Whilst in reasonable agreement, the variation was believed to result from the differences in probe substance (liquid in contact angle and solid in AFM method), scale of measurements (contact area 200 nm2 in AFM, several mm2 in contact angle) and possible polar interactions. However, the surface free energy values derived from direct solid-solid interactions in AFM adhesion force measurements may have more relevances in applications that relate to solid-solid interactions, such as in pharmaceuticals. The influence of polar interaction in AFM adhesion force measurements at low relative humidity was further investigated in Chapter 4. The techniques of colloid probe and plasma polymerized coating were employed: Plasma polymerized hexane and allylamine were coated on the surfaces of glass beads mounted on AFM cantilevers. Plasma Polymerized Hexane had only a dispersion surface free energy while plasma polymerized allylamine had both dispersion and polar surface free energy components. The differences in normalized adhesion forces between these two kinds of colloid probes can reveal the influence of polar interactions at low relative humidity in AFM adhesion force measurements. For most samples, the experimental adhesion forces with plasma polymerized allylamine colloid probes were smaller than the theoretical values calculated from dispersion interactions. The polar interactions in such conditions were repulsive so they had decreased the experimental adhesion forces. So in AFM adhesion force measurements, the polar interactions existed even at very low humidity. However the relative magnitude of polar interactions were smaller than the dispersion interactions and for silicon sample the polar interactions were negligible. In Chapter 5, properties including Young’s modulus, melting points and phase transition temperature were measured at the nanoscale with AFM, SThM and the nano-TA system. The variation of Young’s modulus with temperature, for the excipients hydroxypropylmethylcellulose (HPMC), dibasic calcium phosphate dihydrate (DCPD) was studied. The differences in Young’s modulus between DCPD and its anhydrous form were revealed with AFM measurements. The melting point and phase transition temperature were measured by nano-TA system with sub-100 nm spatial resolution. The thermal properties obtained from nano-TA system were consistent with those from bulk measurements using DSC: e.g. the dehydration of lactose monohydrate (150 ºC) was confirmed by nano-TA system and DSC measurements. In Chapter 6, the methods to derive surface free energy and thermal properties described in previous chapters were employed to spatially locate and characterize an API (AZD 3409 malate salt) and excipient (lactose monohydrate) on the surface of a model tablet at the nanoscale using AFM and the nano-TA system. The API and excipient were mixed with the ratio of 20:80. 50:50 and 80:20 w/w and compressed into discs to create the model tablets. The surfaces of model tablets were first characterized by ATR-IR, NIR and ToF-SIMS. Then AFM adhesion force measurements were carried out to map the location of each component in the mixed discs. In addition, in situ topography AFM images of the discs were recorded. At the position of force mapping, the nano-TA system was employed to correlate the thermal properties including the melting points of both materials and the dehydration of the lactose monohydrate with surface free energy information from force mapping. The surface free energy and thermal properties data were consistent with bulk measurements in previous chapters. In situ correlation between AFM force mapping (surface energy) and nano-TA system (thermal properties) at 5 differences positions on a model disc surface showed consistent identification of the two materials. This proof of principal work can be extended to more complex formulations and has the potential to be employed in early stage solid state stability testing to identify the appearance of new species at surfaces or solid-solid interfaces.
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Fridgeirsdottir, Gudrun A. "The development of a multiple linear regression model for aiding formulation development of solid dispersions." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/52176/.
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As poor solubility continues to be problem for new chemical entities (NCEs) in medicines development the use and interest in solid dispersions as a formulation-based solution has grown. Solid dispersions, where a drug is typically dispersed in a molecular state within an amorphous water-soluble polymer, present a good strategy to significantly enhance the effective drug solubility and hence bioavailability of drugs. The main drawback of this formulation strategy is the inherent instability of the amorphous form. With the right choice of polymer and manufacturing method, sufficient stability can be accomplished. However, finding the right combination of carrier and manufacturing method can be challenging, being labour, time and material costly. Therefore, a knowledge based support tool based upon a statistically significant data set to help with the formulation process would be of great value in the pharmaceutical industry. Here, 60 solid dispersion formulations were produced using ten, poorly soluble, chemically diverse APIs, three commonly used polymers and two manufacturing methods (spray drying and hot-melt extrusion). A long term stability study, up to one year, was performed on all formulations at accelerated conditions. Samples were regularly checked for the onset of crystallisation during the period, using mainly, polarised light microscopy. The stability data showed a large variance in stability between, methods, polymers and APIs. No obvious trends could be observed. Using statistical modelling, the experimental data in combination with calculated and predicted physicochemical properties of the APIs, several multiple linear regression (MLR) models were built. These had a good adjusted R2 and most showed good predictability in leave-one-out cross validations. Additionally, a validation on half of the models (eg. those based on spray-drying models) using an external dataset showed excellent predictability, with the correct ranking of formulations and accurate prediction of stability. In conclusion, this work has provided important insight into the complex correlations between the physical stability of amorphous solid dispersions and factors such as manufacturing method, carrier and properties of the API. Due to the expansive number of formulations studied here, which is far greater than previously published in the literature in a single study, more general conclusions can be drawn about these correlations than has previously been possible. This thesis has shown the potential of using well-founded statistical models in the formulation development of solid dispersion and given more insight into the complexity of these systems and how stability of these is dependent on multiple factors.
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Meunier, Louis. "Etude de formulations complexes à matrice vitrimère : application aux retardateurs de flamme." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILR079.
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L'ajout de retardateurs de flammes dans les vitrimères par voie additive représente un défi à relever pour obtenir des matériaux commercialisables. En effet, la dynamique des réactions d'échange dans de tels systèmes est complexe, et ces additifs peuvent influer sur cette dernière voire modifier sa cinétique. Dans le cadre de ces travaux de thèse, différents retardateurs de flamme (RF) ont été ajoutés à deux matrices différentes : un vitrimère PBT et un vitrimère époxy et l'influence de ces additifs sur la dynamique des échanges basée sur des réactions de transestérification étudiée. La première partie de ce travail s'est intéressé à l'effet de l'incorporation de RF lors de la synthèse du vitrimère PBT par extrusion réactive. Il a été démontré que l'utilisation de sels de phosphinate peut significativement accélérer la transestérification tout en conservant leurs propriétés retardatrices de flamme. En ce qui concerne les résines époxy, deux approches ont été suivies. La première consistait à formuler un matériau intumescent via l'ajout d'additifs dans le but d'obtenir un revêtement protecteur. Le matériau obtenu présente de bonnes performances au feu et sa recyclabilité a été mise en évidence. Dans une seconde approche, une comparaison a été établie entre un retardateur de flamme spécifique ajouté à une matrice époxy par voie réactive ou additive. Dans ce dernier cas, il a été proposé que la réactivité de l'additif a entraîné des réactions secondaires, menant à la consommation des époxydes disponibles empêchant d'obtenir un réseau fortement réticulé. Ce travail, l'un des premiers à aborder l'effet de l'ajout d'additifs retardateurs de flamme dans les vitrimères, montre que les interactions matrice/charge peuvent avoir des effets significatifs sur les réactions d'échange, et que dans le cas de la transestérification, la dynamique de ces réactions peut être affectée même si elle est maintenue<br>The addition of flame-retardant additives into vitrimers represents a challenge that has to be considered to obtain marketable materials. Indeed, the dynamics of the exchange reactions in such systems is complex and such additives may affect it or even modify its kinetics. In this work, various flame-retardant were added into two different matrices: a PBT vitrimer and an epoxy vitrimer considering the exchange dynamics within the networks based on transesterification reactions. In the first part, the effect of incorporating flame-retardant during the synthesis of PBT vitrimer through reactive extrusion was studied. It was shown that the use of phosphinate salts significantly accelerate transesterification, while their flame retardant action were maintained. As far as epoxy are concerned, two approaches were followed. The first formulation consisted of adding intumescent formulations to a vitrimer coating. The material exhibited good flame-retardancy behavior and recyclability. Secondly, a comparison was dressed between a specific flame-retardant added into an epoxy matrix through a reactive or additive pathway. In this case, the fast reactivity of the flame-retardant leads to side reactions, depleting the available epoxies and preventing the formation of a highly cross-linked network. This work, among the first one dealing with the effect of the addition of flame retardant additives in vitrimer shows that it is not a trivial topic and in the case of transesterification, the dynamic of the exchange reaction may be affected even if it is maintained
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Tremblay, Denis. "Influence des différents paramètres de formulation et optimisation des enrobés à matrice de pierre." Mémoire, École de technologie supérieure, 2001. http://espace.etsmtl.ca/843/1/TREMBLAY_Denis.pdf.
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L'orniérage est devenu un problème courant sur plusieurs chaussées. L'augmentation du trafic en nombre et en masse est de plus en plus une cause déterminante de la dégradation des pavages en enrobés bitumineux. Les enrobés conventionnels n'arrivent plus toujours à répondre à la tâche. Face à cette problématique, les enrobés à matrice de pierre sont très avantageux. Ils possèdent également d'autres caractéristiques qui les rendent intéressants, comme leur texture superficielle plus grenue.
Cette recherche vise à établir, à partir de la revue de la documentation, les caractéristiques importantes qu'on doit chercher chez les matières premières des enrobés à matrice de pierre, ainsi que les critères de performance qu'on doit viser, en fonction de l'utilisation ciblée. Autour d'une formulation de base, un programme expérimental sera développé pour étudier l'influence de cinq paramètres de formulation: le type de fibre, le dosage en fibres, la proportion de gros granulat, la proportion de particules fines et la teneur en bitume.
Les phases 2 et 3 du programme expérimental permettront d'optimiser la formulation de base en faisant varier certains paramètres jugés importants ou critiques et de valider la performance de l'enrobé optimisé. Les résultats de la détermination de la résistance à l'orniérage en laboratoire vont montrer que les enrobés à matrice de pierre possèdent une très grande résistance à la déformation par fluage et s'avèrent un choix judicieux pour combattre l'orniérage.
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Amekyeh, Hilda. "Formulation, gastrointestinal transit studies and absorption of amphotericin B-containing solid lipid nanoparticles in rats." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/33437/.
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Successful delivery of pharmaceuticals orally requires a firm understanding of how dosage forms behave during their passage through the gastrointestinal (GI) tract. In this study, the GI transit time and absorption of amphotericin B (AmB) solid lipid nanoparticles (SLN) were investigated in rats, using paracetamol (PAR) and sulphapyridine (SP) as indirect markers. A high encapsulation efficiency of 91.2% was obtained for the AmB SLNs. The SLNs were exhaustively characterised with regards to size, zeta potential (ZP), viscosity, density, migration propensity within agarose gel, in vitro drug release and morphology, to ensure similar disposition in the GI tract after simultaneous oral administration. Freeze-drying did not significantly alter the size or ZP of the AmB SLNs, and in vitro drug release from fresh and freeze-dried SLNs were identical. AmB, PAR and sulphasalazine (SSZ) (the latter being the prodrug of SP) were individually formulated into SLNs using beeswax and theobroma oil as the lipid matrix. The z-averages, polydispersity indices and ZPs of the SLNs ranged from 206.5-224.8 nm, 0.161-0.218 and |61.90|-|71.90| mV, respectively. Gel electrophoresis studies indicated a similar movement propensity among the three SLNs as their migration distances were identical (22.2-22.4 mm) within agarose gel. Scanning electron and atomic force microscopy studies revealed that all three SLNs were spherical in morphology and with similar surface characteristics. The SLNs were assessed for changes in size and surface charge on exposure to simulated GI fluids using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). On contact with the fluids, the particles had a slight increase in size due to ingress of the dissolution media. NTA results were found to be more beneficial than DLS as the latter was biased towards larger particles that were present possibly due to aggregation. After incubation in simulated gastric fluid followed by simulated intestinal fluid (mimicking gastric emptying), all the SLNs were found to be less than 350 nm in size and neutral in charge, which are optimal attributes for intestinal absorption. Time-of-flight secondary ion mass spectroscopic (ToF-SIMS) analyses revealed minimal drug amounts on the surfaces of the particles indicating that drug location was in the core of the SLNs. A developed and validated high-performance liquid chromatography (HPLC) method for simultaneous assay of the drugs in rat plasma using piroxicam as internal standard was found to be sensitive, accurate and precise, with drug recovery from plasma exceeding 92% in each case. A pilot GI transit study conducted in rats showed that the HPLC method was appropriate for the study. In the main study, the effects of food on the transit and absorption of the AmB SLNs were investigated. The presence of food slowed the transit of the SLNs in the GI tract. The gastric transit time of the AmB SLNs was estimated indirectly using PAR and was obtained as 1.71-2.25 hr. Caecal arrival time (CAT) of the AmB SLNs was estimated using SP detection in plasma as SSZ metabolism to produce SP occurs predominantly by the activity of colonic flora. In both fasted and fed states, CAT was 1.80-1.90 hr whereas transit time through the small intestine was 1.65-1.79 hr. A delayed rate of AmB absorption was observed in the fed state however, the extent of absorption was not affected by food. The percentage AmB absorption during the fasted state in the stomach, small intestine and colon were not significantly different from absorption within the respective regions in the fed state. In both states however, absorption was highest in the colon and appeared to be a summation of small intestinal absorption plus absorption proper within the colon. The study indicated that, AmB SLNs irrespective of food status were slowly but predominantly taken up via the lymphatic route and the small intestine was the most favourable site for their absorption. The data obtained indicate that it is possible to enhance the bioavailability of AmB through its incorporation into SLNs. Further enhancement of AmB bioavailability can be achieved through appropriate formulation interventions aimed at slowing transit of the SLNs in the small intestine. Finally, being a lipid-based system, the SLNs may have a potential to reduce the nephrotoxic effects of AmB.
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Snelling, Jonathon R. "Characterisation of pharmaceutical and polymer formulations by novel mass spectrometry approaches." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/55294/.
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Since its inception at the beginning of the twentieth century, the field of mass spectrometry has progressed from the realm of physics to an analytical tool that can be found in many fields of science. This is in large part due to continued development and innovation in instrument design. This thesis explores two significant areas of development in mass spectrometry in the last ten years. The first is the development of ambient ionisation techniques. These techniques require little or no sample preparation, and as a result can provide a rapid means of direct analysis. The second development is the commercialisation of ion mobility – mass spectrometry (IM-MS). This technique enables information on the shape of the analyte of interest to be obtained in addition to its mass-to-charge ratio. The technique has the potential to simplify the spectra acquired from complex mixtures and to separate out isobaric species that cannot be resolved by mass spectrometry alone. Both of these developments have been applied to two important areas of analytical science – the characterisation of pharmaceutical commercial products and synthetic polymer formulations. A modification of the extractive electrospray ionisation (EESI) technique has been developed and has been termed thermally assisted – EESI (TA-EESI). TA-EESI and the atmospheric pressure solids analysis probe (ASAP) have been coupled with IMMS. IM-MS has been used as a rapid separation technique to resolve isomeric species within complex polysorbate formulations. Recently introduced novel polymer architectures synthesised by simple methods have been studied using IM-MS experiments.
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Franciose, Randall J. "Spin and magnetism : two transfer matriz formulations of a classical Heisenberg Ring in a Magnetic Field /." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 1998. http://handle.dtic.mil/100.2/ADA349716.
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HEIMENDINGER, JOHN. "Matrices semi-solides en gelules a base d'acide acetyl-salicylique : formulation, remplissage sur machine et biodisponibilite chez l'homme." Strasbourg 1, 1987. http://www.theses.fr/1987STR15002.
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Rouy, Emmanuel. "FORMULATION D'UN GEL OXYDANT À MATRICE ORGANIQUE APPLICABLE À LA DÉCONTAMINATION NUCLÉAIRE : PROPRIÉTÉS RHÉOLOGIQUES, ACIDO-BASIQUES ET OZONOLYSE DE LA MATRICE." Phd thesis, Université Montpellier II - Sciences et Techniques du Languedoc, 2003. http://tel.archives-ouvertes.fr/tel-00006793.
Full textAbstract:
Un gel fortement acide et oxydant, à matrice purement organique, a été formulé dans l'objectif de l'appliquer sur des parois métalliques contaminées par des radioéléments. Les propriétés rhéologiques pertinentes au regard de l'application envisagée (caractère rhéofluidifiant, thixotropie, seuil d'écoulement...) ont été analysées dans différents milieux : purement aqueux, acide (HNO3 2 mol/kg), acide et cérique ( (NH4)2Ce(NO3)6 1 mol/kg). La matrice organique utilisée, le xanthane, présente pour de faibles concentrations massiques (1 à 2 %) des caractéristiques exceptionnelles dans de tels milieux, même si sa résistance à l'oxydation est limitée à quelques heures. La complexation des sites polaires du polymère par les espèces cériques nous a ensuite amené à explorer les propriétés acido-basiques du xanthane par potentiométrie et RMN du proton. Enfin, un dispositif d'ozonolyse a été mis en œuvre afin d'éliminer la matière organique résiduelle contenue dans les effluents issus du traitement décontaminant. Cette technique s'est révélé efficace en milieu acide mais limitée en milieu acide et cérique. Ce dernier aspect mérite d'être approfondi en vue d'une utilisation dans l'industrie nucléaire.