Carbamazepine (CBZ) is a first-line drug used for the treatment of partial and tonic-clonic seizures. It is also the drug of choice for use during pregnancy and recommended for the treatment of seizure disorders in children. CBZ possesses the ability to induce metabolism of drugs that are transformed in the liver and has the unique ability to induce its own metabolism by a phenomenon known as ‘auto- induction’, where its biological half-life is significantly reduced during chronic administration. Large doses of CBZ are often prescribed as daily divided doses and this often adversely affects patient compliance, with the result that therapy is ineffective. A sustained-release dosage form containing CBZ is currently marketed as Tegretol® CR and the development of a generic product would provide patients with an equivalent product with a similar dosing frequency, at a reduced cost. Therefore, the development of a polymer-based matrix tablet was undertaken to produce a sustained-release dosage form of CBZ, since these dosage forms are relatively simple and cheap to produce when compared to other, more sophisticated forms of sustained-release technology. Preformulation studies were conducted to assess moisture content of excipients and dosage forms and to identify possible incompatibilities between CBZ and potential formulation excipients. Furthermore, studies were conducted to assess the potential for polymorphic transitions to occur during manufacture. Stability testing was conducted to assess the behaviour of the dosage forms under storage conditions that the product may be exposed to. Dissolution testing was undertaken using USP Apparatus 3, which allowed for a more realistic assessment and prediction of in vivo drug release rates. Samples were analysed using a high performance liquid chromatographic method that was developed and validated for the determination of CBZ. Tablets were manufactured by wet granulation and direct compression techniques, and the resultant drug release profiles were evaluated statistically by means of the f1 and f2 difference and similarity factors. The f2 factor was incorporated as an assessment criterion in the design of an artificial neural network that was used to predict drug release profiles and formulation composition. A direct compression tablet formulation was successfully adapted from a prototype wet granulation matrix formulation and a number of formulation variables were assessed to establish their effect(s) on the dissolution rate profile of CBZ that resulted from testing of the dosage forms. The particle size grade of CBZ was also investigated and it was ascertained that fine particle size grade CBZ showed improved drug release profiles when compared to the coarse grade CBZ which was desirable, since CBZ is a highly water insoluble compound. Furthermore, the impact of the viscosity grade and proportion of rate-controlling polymer, viz., hydroxypropyl methylcellulose was also investigated for its effect on drug release rates. The lower viscosity grade was found to be more appropriate for use with CBZ. The type of anti-frictional agent used in the formulations did not appear to affect drug release from the polymeric matrix tablets, however specific compounds may have an effect on the physical characteristics of the polymeric tablets. The resultant formulations did not display zero-order drug release kinetics and a first-order mathematical model was developed to provide an additional resource for athematical analysis of dissolution profiles. An artificial neural network was designed, developed and applied to predict dissolution rate profiles for formulation. Furthermore, the network was used to predict formulation compositions that would produce drug release profiles comparable to the reference product, Tegretol® CR. The formulation composition predicted by the network to match the dissolution profile of the innovator product was manufactured and tested in vitro. The formulation was further manipulated, empirically, so as to match the in vitro dissolution rate profile of Tegretol® CR, more completely. The test tablets that were produced were tested in two health male volunteers using Tegretol® CR 400mg as the reference product. The batch used for this “proof of concept” biostudy was produced in accordance with cGMP guidelines and the protocol in accordance with ICH guidelines. The test matrix tablets revealed in vivo bioavailability profiles for CBZ, however, bioequivalence between the test and reference product could not be established. It can be concluded that the polymeric matrix CBZ tablets have the potential to be used as a twice-daily dosage form for the treatment of relevant seizure disorders.

Conventional solid dosage forms often lead to fluctuations which exceed the maximum safe therapeutic level and/or decline below the minimum effective level. It is recognised that many drugs for chronic administration should be administered on a schedule that maintains plasma drug concentration within the therapeutic window. Research in controlled release dosage forms aims at designing a system with a zero-order input (eg, ideally to deliver 8.33% of the dose per hour over a 12 hour duration), producing steady state plasma drug levels. Oral dministration of drugs prepared as a controlled release formulation is extremely popular, and has attracted the attention of pharmaceutical scientists during the last decade. This has been due to the simultaneous convergence of various factors (eg, discovery of novel polymers and devices, better understanding of formulation and physiological constraints, expiration of existing patents, prohibitive cost of developing new drug entities), involved in the development of these delivery systems. Controlled release oral products can be formulated as single or multiple unit dosage forms and the relative merits of multiple unit forms with their own rate controlling systems are well established. This work describes the development of a relatively inexpensive multiple-unit capsule dosage form of theophylline containing coated mini-tablets for drug delivery throughout the gastrointestinal tract. Preformulation studies on theophylline anhydrous included solubility and dissolution rate determinations. Techniques including X-ray powder diffraction, differential scanning colorimetry and infrared spectroscopy provided no evidence of true polymorphism after recrystallisation from various solvents. However, scanning electron micrographs showed the effects of solvent polarity and cooling rate on the size and shape of recrystallised particles. Theophylline granules were manufactured by using various binders and were film coated by fluidised bed technology with various proportions of ethylcellulose, containing varying amounts of PEG 1540. In vitro release rates were dependent upon coating thickness and the proportion of PEG, which, being water soluble, created pores in the coating during dissolution studies as observed by a scanning electron microscope. However, substantial proportions of the drug remained unreleased from the granules. In order to overcome the problems of drug retention, plain granules were used and theophylline mini-tablets (3 mm diameter, weighing 15 - 20 mg) were manufactured and film coated with various Eudragits ® and other polymeric mixtures (soluble and insoluble). In vitro dissolution profiles from samples enclosed in hard gelatin capsules were determined using the USPXXI paddle apparatus in test media at pH 1.2 (HCI), pH 5.4 and 7.4 (phosphate buffers) at 37'C. Monitoring of in vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in < 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasise the usefulness of an animal model for assessment of in vivo drug release and subsequent absorption during the development of modified release dosage forms. Mini-tablets were subjected to isothermal and cyclic stresses to reach conditions for up to 6 months at different temperatures and relative humidity. The film integrity was maintained but ageing of the coating occurred which impeded dissolution. Reduced drug release was temperature related while the effect of relative humidi% was insignific~t. Encapsulated mini-tablets (uncoated and coated with Eudragit RL and RS 2% w/w) equivalent to a 300 mg dose, were evaluated both in vitro and in vivo using beagle dogs. The pharmacokinetic parameters from single and multiple dose studies showed several advantages over Theo-Dur® 300 mg tablets. Precise dosage titration is possible by careful adjustment of the number of encapsulated mini-tablets. This multiple unit mini-tablet delivery system will allow for greater flexibility in dosage adjustment compared to the currently available preparations, allowing individualised fine dose titration in those patients requiring therapeutic drug monitoring. The developmentof the multiple unit mini-tablet formulation appears to provide an optimal dosage form with maximum flexibility in respect of dose, duration range and ease of production.

Les recherches menées ont pour objectif de dresser un bilan, le plus exhaustif possible, sur la céramique gallo-romaine de la partie occidentale de la province de Lyonnaise définie par les territoires des civitates des Vénètes, des Coriosolites, des Osismes et des Riédons. Cette synthèse régionale à d'abord consisté en l'élaboration d'un catalogue de formes, puis d'une approche typo-chronologique. Ce premier corpus est constitué de 792 formes qui se répartissent en 20 grandes catégories techniques et fonctionnelles. Un système de classement ouvert a été employé afin de pouvoir être complété en fonction des nouvelles découvertes. L'analyse de 34 assemblages de céramique issus de 21 sites a permis de définir huit horizons chronologiques couvrant la période de la seconde moitié du Ier s. av. J.-C. jusqu'aux premières décennies du IVe s. ap. J.-C. Ces horizons offrent un premier aperçu de l'évolution des céramiques consommées et des stratégies d'approvisionnement au cours de cette période. / The research aim to take stock, as exhaustive as possible, on the Gallo-Roman ceramic of the western part of Lyonnaise province defined by the territories of the civitates of the Veneti, of Coriosolite, of Osismii and Redones. This regional summary presents the development of a catalogue of forms and a typo chronological approach. This first corpus is composed of 792 forms divided into 20 major technical and functional categories. An open ranking system was used in order to make additions according to new discoveries. The analysis of 34 pottery assemblages from 21 sites defined eight horizons from the second half of the 1st century BC until the first decades of the 4th century AD. They offer a first look of the evolution of consumed ceramics and supplying strategies during this period.

There has been limited research done to determine the impact of the use of colour on communication displays in the facilitation of graphic symbol location within an overlay. As many Augmentative and Alternative Communication systems are pictorial in nature, it is of importance that interventionists are aware of the potential impact that colour can have on the accuracy and rate of symbol location. The present study is based on a study by Wilkinson, Carlin and Jagaroo (2006) and used the same testing material (colour conditions) whilst modifying the type of exposure to these colour conditions. This study investigated the effect of sequential exposure of colour conditions on the rate and accuracy of graphic symbol location. The study used a comparative, non-experimental group design using sixty participants who conformed to specific selection criteria. Each participant was exposed to three colour conditions that were placed in a specific sequential order. The participants were required to match a target, graphic symbol within an array of symbols in the differing colour conditions. Two different types of graphic symbols were used meaningful (Type A) and arbitrary (Type B). Two different colour sets were also used with the colour conditions varying in each set. Set 1 were the sequentially ordered colour conditions of same colour, mixed colour and unique colour symbols (difficult to easy) while Set 2 were the sequentially ordered colour conditions of unique colour, mixed colour and same colour symbols (easy to difficult). The major findings of the study were as follows. In terms of rate, there was a significant interaction noted between the two symbol types and their sequential ordering. The time taken (rate) for the location of the nonreferential forms was slower than that taken for the meaningful symbols. The reasoning behind this result could be that the non-referential forms were not as familiar to the participants as the meaningful symbols were. Thus, the rate recording of the meaningful symbols and the non-referential forms described in the three colour conditions was different and could be noted in the results. In terms of accuracy, a significant impact was noted between the two symbol types when the first manner of sequential ordering was used, however, there were no significant differences noted when the second manner of sequential ordering was used. This implies greater accuracy was recorded when the second manner of sequential ordering was used as this ordering appeared to be “visually easier” for the location of symbols. / Dissertation (MA)--University of Pretoria, 2009. / Centre for Augmentative and Alternative Communication / unrestricted

No description available.

For centuries, the theory and principles of diplomatics have played a role in the work of European archivists. In North America, however, its relevance is still under scrutiny. This thesis employs diplomatic analysis to test its validity when applied to modern documents and procedures. To investigate the significance of diplomatic methodology and analysis, this thesis first discusses the recent history and structure of the British Columbia court system. It then examines a selection of case files from the civil, probate and bankruptcy registries, and it assigns the documents within to one of the six phases of a procedure: initiative, inquiry, consultation, deliberation, deliberation control, and execution. The study concludes by discussing the diplomatic character of the procedures and its importance in the understanding of modern records. More specifically, it outlines how diplomatics and procedural analysis can assist records professionals in the development of classification systems and retention and disposition schedules; the design of automated records management systems; and archival appraisal, arrangement and description. / Arts, Faculty of / Library, Archival and Information Studies (SLAIS), School of / Graduate

The theory of Riemann surfaces is quite old, consequently it is well developed. Riemann surfaces originated in complex analysis as a means of dealing with the problem of multi-valued functions. Such multi-valued functions occur because the analytic continuation of a given holomorphic function element along different paths leads in general to different branches of that function. The theory splits in two parts; the compact and the non-compact case. The function theory developed on these cases are quite dissimilar. The main difficulty one encounters in the compact case is the scarcity of global holomorphic functions, which limits one’s study to meromorphic functions. This however is not an issue in non-compact Riemann surfaces, where one enjoys a vast variety of global holomorphic functions. While the function theory of compact Riemann surfaces is centered around the Riemann-Roch theorem, which essentially tells us how many linearly independent meromorphic functions there are having certain restrictions on their poles, the function theory developed on non-compact Riemann surface engages tools for approximation of functions on certain subsets by holomorphic maps on larger domains. The most powerful tool in this regard is the Runge’s approximation theorem. An intriguing application of this is the Gunning-Narasimhan theorem, which says that every connected open Riemann surface has an immersion into the complex plane. The main goal of this project is to prove Runge’s approximation theorem and illustrate its effectiveness in proving the Gunning-Narasimhan theorem. Finally we look at an analogue of Gunning-Narasimhan theorem in the case of a compact Riemann surface.

In this dissertation, I argue for the philosophical consistency of Aquinas’ hybrid view of human souls - that is, the idea that human souls, and only human souls, are at once substantial forms and subsistent things. I contend that the best way to understand the ontological status of human souls according to Aquinas is by means of the concept of ‘subsistent parts’. Since Aquinas characterizes souls as parts of substances, I propose a mereological analysis of the different types of part in Aquinas, and I conclude that souls should be seen as metaphysical parts of substances. An influential contemporary view holds that Aquinas’ doctrine is inconsistent on the grounds that nothing could be an abstract (form) and a concrete (subsistent) at the same time. I respond to this view by denying the widespread notion that substantial forms are purely abstract entities. I hold that the best way to make sense of Aquinas’ twofold approach to human souls is by saying that substantial forms possess an element of concreteness which is accounted for by the fundamental relationship between form and being. Finally, I address the question of taxonomy: how can we classify Aquinas’ view of the soul-body relation in light of the concepts that are currently used in philosophy of mind. I argue that the notion of a subsistent part entails the concept of ‘part-dualism’, which I present as standing midway between substance-dualism and nonreductive materialism, and also as being ontologically richer than property-dualism. I conclude this dissertation with a refutation of the idea championed by some prominent scholars that the existence of the soul is sufficient for the existence of the person.

The aim of the thesis is to analyze the factors that influences women's return to labor market after maternity leave in Prachatice district between years 2008 and 2015. Based on the teoretical resources there are created questions of semi-structured interview which is conducted with sixteen women from Prachatice district with children at age from 0 to 7 years. The part of the thesis is also analysis of labor market in the district in mentioned time period using the data relates to the employment and unemployment of women. Based on the results, the hypotesis is verified:"Women in Prachatice district deemed the return to the labor market after maternity leave as complicated and local labor market does not fit to their requirements." Women find job offers for mother with children as deficient, shows heavily dependence on help from extended family, in district is low supply of care facilities for younger children, operating time of kindergartens doesn't correspond to the needs of working mothers. The study includes recommendations for Prachatice district suggested by author which are added-value to the thesis. There is no study dealing with the situation of women in labor market yet, the results might be a stimulus for further researches.

Notre recherche consiste à poser l'hypothèse d'une mise en relation entre le genre et l'écriture journalistique : en effet, peut-on envisager l'existence d'un lien entre l'écriture journalistique et le genre ? Autrement dit, le genre peut-il avoir une influence quelconque sur l'écriture journalistique ?Pour essayer de trouver des éclaircissements, nous avons travaillé sur la presse écrite algérienne et plus exactement sur le quotidien « La voix de l'Oranie ». Nous avons donc procéder à une analyse lexicale, dans un premier temps, et syntaxique, dans un second temps, de 36 articles de six journalistes, dont trois femmes et trois hommes, du quotidien en question. Par la suite, nous avons établi une comparaison entre les écrits des journalistes femmes et hommes et on a pu relever 13 différences en sémantiques lexicales : la formulation des titres, la fonction du chapeau, l'implication des interlocuteurs, la visée de leurs écrits, la beauté du texte, l'emploi des répétitions, des adjectifs, l'objectivité vis-à-vis de l'information, le niveau de langue employé ainsi que la nature du texte. Et 19 dissemblances en typologie textuelle, notamment dans la formulation des titres et des phrases, le choix des énoncés dialogiques, les rapports logiques, le choix des verbes, l'emploi des expressions détachées, la manière de l'implication de chaque journaliste, l'emploi du discours rapporté, pour ne citer que cela.Mais avant ce travail, nous avons d'abord commencé par faire le tour de la question du point de vue théorique ou nous avons sollicité de nombreuses recherches sur la question de la différence entre les femmes et les hommes, et ce, dans les différents domaines. / Our research involves the hypothesis of a relationship between the gender and the journalisticwriting: indeed, can one consider any association between the journalistic writing and the gender?In other words, can the gender have any influence on journalistic writing?To try to find explanations, we work on the Algerian written press and more exactly “La voix de l'Oranie”.We have therefore proceeded to a lexical analysis, previously, and syntactic one, in a second time, of 36 articles of six journalists, of which three women and three men, of the Newspaper in question. Afterward, we established a comparison between the manuscripts of the journalists women and men, One could raise 13 differences in lexical semantic: titles' formulation, the function of the hat , the interlocutors' implication , their writings' aiming, text's beauty, the use of repetitions and adjectives, the objectivity against information, the employed language level as well as the nature of the text. And 19 dissimilarities in literal typology, notably in titles' and sentences' formulation, the choice of dialogical statements, the logical reports, the choice of verbs , the use of the detached expressions , the implication's manner of each journalist, the job of the retrieved speech, to quote only that.But before this work, we first started by making an overview of the theoretical point of view where many researches were solicited on the difference between women and men in different fields.