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.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-07-13T14:23:21Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação de Mestrado Augusto - Versão Final - 05.07.16.pdf: 2539433 bytes, checksum: 5317f34435773775b8fcf0c7526d78d5 (MD5) / Made available in DSpace on 2017-07-13T14:23:21Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação de Mestrado Augusto - Versão Final - 05.07.16.pdf: 2539433 bytes, checksum: 5317f34435773775b8fcf0c7526d78d5 (MD5) Previous issue date: 2016-05-27 / O pantoprazol é, atualmente, um dos medicamentos mais utilizados para tratamento das doenças gástricas por seu mecanismo de ação conhecido e eficácia comprovada na inibição da secreção de ácido no lúmen estomacal, contudo o tratamento prolongado e os efeitos causados pelas gastropatias exigem tratamentos específicos e mais abrangentes. O material Vegetal Schinus terebinthifolius Raddi, conhecida como Aroeira, já é utilizada popularmente em feridas cutâneas pelos seus efeitos cicatrizantes e anti-inflamatórios, possui vários estudos comprovando sua eficácia na diminuição das lesões promovidas pelas doenças gástricas. Sabendo-se da existência das formulações Associação em Dose Fixa (ADF), que integram em uma mesma fórmula farmacêutica um insumo farmacêutico sintético e um insumo farmacêutico fitoterápico, o objetivo deste trabalho foi elaborar um forma farmacêutica sólida ADF utilizando doses terapêuticas do pantoprazol e do extrato da Aroeira. Para isto, foi realizada a obtenção do granulado seco de aroeira pela metodologia de secagem por convecção. Assim, os ativos foram misturados a excipientes e transformados em comprimidos, por compressão direta. Os comprimidos obtidos foram submetidos a controle físico-químico e foram realizados testes de doseamento, dissolução e estabilidade acelerada que avaliaram as condições da formulação. Como esperado a dissolução demonstrou liberação do pantoprazol em meio básico e degradação em meio ácido, levando a necessidade de utilização do fármaco em formato de grânulos gastroresistentes. Já os testes de estabilidade realizados nos tempos 0, 3 e 6 meses atestou no curto período a manutenção das características básicas de liberação e teor dos comprimidos que foram mantidos durante o estudo em câmara climática de zona IV. Foi possível, desta forma, estabelecer os parâmetros básicos para o desenvolvimento desta formulação ADF contribuindo para a descoberta de alternativas terapêuticas aos tratamentos convencionais. / Pantoprazole is today one of the most used drugs for the treatment of gastric diseases because its known mechanism of action and proven effectiveness in inhibiting acid secretion in the stomach lumen, but prolonged treatment and the effects caused by gastropathy require specific treatments and more extensive. Schinus terebinthifolius Raddi plant, known as Aroeira, is already commonly used in skin healing by its anti-inflammatory effects, having several studies showing efficacy in reducing gastric lesions promoted by the disease. Knowing the existence of the formulations Association-Dose-Fixed (ADF), which are part of the same pharmaceutical form, a synthetic active ingredient and an active herbal principle, the objective of this study was to develop a solid dosage form ADF using therapeutic doses of pantoprazole and the Aroeira extract. For to obtain the dry granulated were used the method for drying by convection, where the active excipients were mixed and tableted by direct compression. The tablets obtained were subjected to physic-chemical control and tests to determinate their concentrations, their accelerated stability and their dissolution quality who served to evaluate the conditions of the formulation. The obtained values maintained their therapeutic range described in the literature. As expected the dissolution demonstrated release of pantoprazole in basic medium and degradation in acid medium that leads to the need to use the drug in gastroresistant granules format. Since the stability testing at 0, 3 and 6 months attested short period maintaining the basic characteristics of release and content of the tablets that were maintained during the study in climate zone IV camera. It was thus possible to establish the basic parameters for the development of this formulation ADF contributing to the discovery of therapeutic alternatives to conventional treatments.

Magister Pharmaceuticae - MPharm / The overall objective of this research is to attempt to produce, by direct compression, indomethacin tablets which have good dissolution characteristics and an improved bioavailability profile, when compared to the capsule formulations currently available. In order to use the direct compression method, the solubilized form of indomethacin should have good flow properties, as well as a small bulk volume for incorporation into reasonably sized tablets.

The problem for this study is the increasing number of students identified as special need learners in U.S. schools and the critical need to prepare them for success in the 21st century workplace. The purpose of this study was to examine the experiences of special education teachers while they integrate mobile tablets into the classroom. The conceptual framework was based on constructivism, andragogy, experiential learning models and Roger’s diffusion of innovation. The research questions focused on understanding the experiences of special education teachers during their implementation of mobile tablets. This study was a qualitative multiple case study involving the interview special education teachers before and after lessons during which they integrated mobile devices into their classroom. These interviews and curriculum artifacts were analyzed using thematic inductive analysis. Results identified that all the teachers were generally in favor of integrating mobile tablets and believed they were integrating them successfully. However, the teachers who believed in their personal ability to utilize mobile devices in their classrooms were able to navigate multiple issues and integrate them more effectively. The level of integration was also influenced by the usability, functionality and accessibility of the technologies. Additionally, all teachers related their ability to integrate technology successfully with the type and quality of professional development they received. Understanding how special education teachers successfully integrate innovative technologies has the potential to support special needs learners for their future success in the 21st century workplace.

1 Abstract Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Departmanet of Pharmaceutical technology Consultant: doc. PharmDr. Zdeňka Šklubalová Ph.D. Student: Hana Machutková Title of Thesis: Influence of different types and ratios of microcrystalline cellulose and lactose on physical properties of tablet blends and tablets. In this study, the properties of tablet blends prepared from five different kinds of microcrystalline cellulose (Avicel ® A-101, 102, 105, 112, 200) and three types of lactose in different proportions were evaluated. Moisture content, the bulk and tapped density and the angle of repose were compared for tablet blends. The addition of lactose to the mixtures caused the decrease in the moisture content in the tablet blends. After evaluating the flow properties, the mixtures with suitable characteristics were compacted at compression forces of 8 and 12 kN. The force required to eject the tablet, the table strength, the disintegration time and the friability of the resulting tablets were estimated. The worst compressibility was identified for mixtures with higher concentration of Avicel 105. Due to its very small and fine particles (approximately 20μm) the filling of matrix was not uniform making tablet compression unsuccessful and thus the of uniform...

New technologies related to mobility, such as smartphones and tablets, once again push companies to reconsider their IT system. New services can be provided externally (to customers, partners or the general public) as well as internally (to employees) and existing ones have to be reconsidered to fit new devices and new ways of using IT. This important evolution implies that new technologies and new components are integrated in the IT system. Those components are characterized by a high volatility: they are subject to trend effects, they evolve quickly to follow the terminals market and thus their lifetime is far from guaranteed. This study focuses on new uses brought by mobile technologies and that modern companies can benefit from, and then, based on several market products, proposes a set of software architecture patterns that correspond to the different possible implementation of mobility in the IT system.

Society has undergone major and revolutionary changes in a relatively short time, where the individual is surrounded by and has become increasingly dependent on digital technology and programmed objects. The availability of digital tools such as digital tablets (e.g. iPads) has increased significantly in the Swedish preschool, even though research in this area is limited. It is therefore of utmost importance to examine how teachers use digital tablets to support children's learning, both in general but also in relation to technology education, where the latter also includes computer programming. This thesis intends to contribute to such an examination in the form of two studies. In study 1, an online survey was used that consisted of 26 questions that were sent across Sweden and in which 327 respondents participated. Questions were posed about how teachers work with digital tablets together with preschool children. Specifically, the following research questions were raised: What educational activities with digital tablets do teachers engage in Swedish preschools? What are teachers’ views of the educational benefits and disadvantages of using digital tablets in teaching? and, What are teachers’ recommendations for using digital tablets in their teaching practice? In study 2, another online survey was developed based on the findings from study 1 and contained 16 questions that resulted in 199 responses from across Sweden. In study 1, teacher responses around programming proved prominent, which study 2 aimed to explore more deeply. Therefore, the survey questions adopted in the second study probed how preschool teachers implemented programming activities during preschool teaching. Results from the two studies showed that despite a lack of competence, equipment and support from school leadership, numerous teachers often develop and use their own initiative to integrate digital tablet and programming activities in preschool. Teachers communicated several advantages of programming activities with respect to children's learning, aspects that were linked to the notions of 21st century skills and computational thinking. When it comes to methods for designing and implementing activities in practice, several connections to Papert's constructionism were seen as meaningful for the children, where activities contained a large degree of project based work with room for promoting children's agency. The results of the research clearly indicates that solid teacher-initiated work with digital tools as pedagogical resources is underway in earnest across Swedish preschools. In order to realize the advantages of teachers’ development of digital tablet activities for learning, teachers must be provided with prerequisite support necessary for an optimal integration of digitization tools into preschool education. In this regard, teachers should be offered competence development, as well as time for effective implementation, planning and follow-up. Access to appropriate digital tools is also a proviso for realizing this mandate. Increased collaboration between school managers and teachers would also further steer such initiatives in a positive pedagogical direction.

The purpose of this review of literature was to understand the role of mobile device applications in health related conditions and to analyze their effects on health outcomes related to the management of chronic illnesses. Implications for future use of applications in client-centered care and interpretation of the data by health care providers was also explored. Peer-reviewed, English-language research articles published from 2008 to present were included for synthesis. Study results revealed positive outcomes when health-related mobile applications were used in practice and support clinicians' use of mobile applications as a tool for monitoring symptoms and communicating with individuals. The literature indicated nurses play a significant role in providing feedback, which reinforces self-care strategies and adherence, with the potential for improving outcomes. Additional research is needed to evaluate the long-term effects of applications on patient outcomes, nurses' perspectives, and feasibility of implementation into practice.

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