As formas orais sólidas são as mais utilizadas pela sua facilidade de administração e transporte, além de proporcionarem maior estabilidade, se comparadas às líquidas ou semi-sólidas. Dentre os sólidos orais, os comprimidos destacam-se por apresentarem processo de fabricação relativamente fácil, com alta produtividade e baixo custo. A compressão direta é o método preferencial para a produção de comprimidos pois economiza tempo e energia, é ambientalmente menos agressiva e reduz investimentos em equipamentos e na estrutura da área de produção, por requerer menor número de etapas no processamento que os métodos tradicionais de granulação. A principal limitação para a aplicação desse processo é a baixa capacidade de compactação dos fármacos que requerem altas concentrações para obtenção do efeito terapêutico. Com o objetivo de desenvolver formulações contendo alto teor de fármaco por compressão direta foi utilizado o planejamento estatístico de mistura e o paracetamol como fármaco modelo, pelas propriedades deficientes de escoamento e compactação. O programa Design Expert® foi empregado e forneceu 19 formulações, que foram produzidas e avaliadas quanto ao índice de compressibilidade, ângulo de repouso, umidade, peso médio, friabilidade, dureza, doseamento, desintegração e dissolução. O programa Design Expert® foi alimentado com os resultados obtidos e as formulações foram otimizadas. A formulação otimizada que atendeu a todos os parâmetros de qualidade foi produzida e analisada. Os resultados encontrados foram muito próximos aos previstos pela análise de regressão, demonstrando que o projeto de mistura é uma ótima opção para a pesquisa e desenvolvimento, diminuindo o tempo despendido e o número de experimentos. / The solid oral forms are widely used, by easy administration and transport. They provide larger stability than a liquid or semi-solid. Among the solids orals the tablets appear for they present production process relatively easy, with high productivity and low cost. The direct compression is the preferential method for the production of tablets because is less aggressive for the environment, saves time and energy and reduces investments in equipments and in the structure of the production area, for requiring smaller number of stages in the production\'s process than the traditional methods of granulation. The main limitation for the application of that process is the low compaction capacity of the drugs that require high percentages for the therapeutic effect. The aim of this study was developing formulations containing high amount of drug by direct compression using the statistical planning of mixture and the paracetamol as drug model, for the deficient flow and compaction properties. The program Design Expert® was used and supplied 19 formulations that were produced and the compressibility index, angle, humidity, weight, friablility, hardness, assay, disintegration and dissolution were analyzed. The program Design Expert® was fed with the obtained results and the formulations were optimized. The formulation optimized that assisted all quality parameters was produced and analyzed. The obtained results were very close with the regression analysis, demonstrating that the mixture project is a great option for the research and development, reducing the spent time and the number of experiments.

There are today strong incentives for an increased understanding of material properties and manufacturing processes to facilitate the development of new technologies in the pharmaceutical industry. The purpose of this thesis was to suggest methods requiring a low sample amount for characterization of technical properties of powders. Compression analysis was used to evaluate the formulation relevance of some compression equations. Using the mechanics of single granules to estimate powder functionality was part of this work. It was concluded that the formability of granular solids and the plasticity of single granules could be determined with compression analysis by using the Kawakita model for single components and binary mixtures of ductile granules. Further on, the fragmentation propensity of solid particles could be estimated from compression analysis by using the Shapiro equation, enabling indicators of both the fragmentation and the deformation propensity of particles to be derived in one single compression test. The interpretations of the compression parameters were only valid if the influence of particle rearrangement was negligible for the overall compression profile. An index indicating the extent of particle rearrangement was developed and a classification system of powders into groups dependent on the incidence of particle rearrangement was suggested as tools to enable rational interpretations of compression parameters. The application of compression analysis was demonstrated by investigating the relevance of the mechanics of granular solids for their tableting abilities. The plasticity of single gran-ules was suggested to influence both the rate of compactibility and the mode of deformation, and consequently the maximal tablet strength. The degree of granule bed deformation was shown to be a potential in line process indicator to describe the tableting forming ability. This thesis contributes to a scheme, suitable in formulation work and process control, to describe manufacturability of powders for an enhanced tablet formulation technology.

<p>Godkännandedatum: 2015-01-02</p>

In 1994, two batches of unearthed Chu 楚 bamboo slips from the Warring States period (Zhanguo shidai 戰國時代, 475–221 B.C.), totaling 1200 pieces and featuring over 35000 characters, appeared in the cultural relic market of Hong Kong. These slips, highly valuable for philological research, cover nearly 100 kinds of ancient Chinese classic. They were soon collected by the Shanghai Museum for restoration and analysis, and have, since 2001, been published in successive volumes entitled Shanghai bowuguan cang Zhanguo Chu zhushu 上海博物館藏戰國楚竹書, eight volumes of which have been issued to date. My study focuses on the seventh volume, published in 2008, comprising five chapters — Wuwang jian zuo 武王踐阼, Zhengzi jia sang 鄭子家喪, Jun ren zhe hebi an zai 君人者何必安哉, Fan wu liu xing 凡物流形, and Wuming 吳命— comprehensive annotation and transcription of which have been provided by the volume editor. In spite of the efforts put on interpreting these bamboo texts, existing researches have their limitations; some intricate textual problems remain to be solved. The present dissertation attempts to examine the elucidations and interpretations of these bamboo texts in order to identify and screen out erroneous views among them. Sophisticated investigation on several controversial issues has been carried out to determine and restore the intent of the original passages. / published_or_final_version / Chinese / Doctoral / Doctor of Philosophy

Since the antiquity, the Book of Change (Zhouyi 周易) has been praised as the leading scripture among the five classics (with the Book of Documents [Shangshu 尚書], the Book of Odes [Shijing 詩經], the Spring and Autumn Annals [Chunqiu 春秋], and the Book of Rites [Liji 禮記]), and the supreme dao of the three mysteries (with Laozi 老子 and Zhuangzi 莊子). However, its guayaoci 卦爻辭 (general and line judgments of the hexagrams) are not only recondite but also proliferate with conflicting exegeses that lead nowhere. Fortunately, multiple early manuscripts of the Book of Change, including those from the Mawangdui 馬王堆 silk texts, the Fuyang 阜陽 bamboo slips, and the Chu 楚 bamboo slips housed at the Shanghai Museum, were excavated over the past forty years. These, combined with other related archaeological findings, found the basis for a scrupulous reading of the guayaoci. I attempt to compare the Shanghai Museum manuscript, which is the earliest extant copy of the Book of Change, with the traditional editions and other excavated copies to arrive at a reasoned exposition based on previous interpretation and through manifold research methods such as philology, textual criticism and theosophy. The present thesis examines seven guyaoci from seven hexagrams: 1 “li yong qin fa 利用侵伐” of the fifth line of qian 謙; 2 “bu fu yi qi lin 不富以其鄰” of the fifth line of qian 謙 and the fourth line of tai 泰, and “fu yi qi lin 富以其鄰” of the fifth line of xiaochu 小畜; 3 the naming of wuwang 无妄 and its meaning; 4 “wuwang zhi ji, wu yao you xi 无妄之疾，勿藥有喜” of the fifth line of wuwang 无妄; 5 “he tian zhi qu 何天之衢” of the sixth line of dachu 大畜; 6 “lu suosuo, si qi suo qu zai 旅瑣瑣，斯其所取災” of the first line of lu 旅; and finally 7 “ru you yiru 繻有衣袽” of the fourth line of jiji 既濟. / published_or_final_version / Chinese / Doctoral / Doctor of Philosophy

The main purpose of this study is to describe and increase the understanding of preschool teachers´ experiences regarding pedagogical documentation with digital tablets. The focus of the study was to reveal how the digital tablets are used for pedagogical documentation. Our hope is to give new meaning concerning ICT, information and communication technology, on a daily basis at preschools. The method that we used in this study is qualitative interviews to reach and get knowledge about preschool teachers´ experiences with digital tablets. In the results we have been able to conclude that the positive properties, such as digital tablets being a fast and simple way of creating pedagogical documentation, that the technique offered were bigger than the negative aspects, which resulted in a general positive outcome. / Uppsatsens övergripande syfte handlar om att beskriva och förstå hur pedagoger upplever arbetet med pedagogisk dokumentation med hjälp av den digitala pekplattan. Numera kan den pedagogiska dokumentationen i förskolan ske snabbt och enkelt genom digitala pekplattor. Det är till exempel enkelt att skicka iväg bilder eller information, direkt i stunden. Det kan givetvis vara mycket smidigt, men vår problematik som vi vill poängtera i detta examensarbete, är att teknikens snabba funktioner och processer kan möjligen minska eftertanken och utrymmet för egna reflektioner. Metoden som vi använder är kvalitativa intervjuer. Resultaten som vi kom fram till i studien var att de positiva egenskaper som tekniken möjliggör överväger de eventuella negativa aspekterna. Resultaten bekräftar att pedagoger i förskolan överlag upplever att deras dokumentationsarbete förenklas med hjälp av den digitala pekplattan. Problemen som vi upptäckte hänvisar alltså till teknikens snabba hantering som eventuellt kan minska möjligheterna för egna reflektioner.

This study explores young children's use of digital tablets in Swedish preschool environments, with special interest in how the use of digital tablets may affect children's agency. A multimodal, design theoretical approach was used, combined with sociology of childhood, to highlight the dynamics between children's agency and the affordances provided by the digital tablets. Two video ethnographic substudies were conducted within two separate preschool settings, including preschools where children use digital tablets to communicate in a minority language. In order to take into account as many modes of communication as possible, video recordings of children's use of the digital tablets was set side-by-side with screen recordings of the digital tablets. Major findings include how children's agency in digital tablet activities is intertwined with the different affordances, as emerging in the children's interaction with one another and the digital tablet. It was found that when affordances were built on visual, auditive and corporeal modes of communication, children's agency was enabled. Such affordances are in this study argued to be more, for the children, apt modes of communication for children to exert agency. Furthermore, it is argued that when children are given the possibility to communicate in their minority language, using for example Skype, this is a form of children's agency. The didactical implications and the societal potentials for children's use of digital tablets in preschools are discussed in relation to the creative skills individuals may need in an unknown future.

Growing numbers of morbidity and mortality due to the cancer and coronary heart disease is recognized as the increasing challenge in the world. The initial stage of these diseases, early diagnosis and treatment are the main objectives of current researches. According to Lithuanian Health Information Centre morbidity and mortality due to these diseases in Lithuania exceed average of European Union. The oxidative stress occurs in cells as a result of normal physiological processes and environmental interactions, and the complex antioxidant defense system are of particular importance in protecting biological systems against oxidative damage by free radicals. Recently polyphenols and anthocyanins containing foods and preparations have attracted attention due to their health promoting benefits. Anthocyanins make one of the main groups of flavonoids, and represent polyphenolic compounds, that are found in vegetables and fruits, particularly in berries. An important effect of anthocyanins is the scavenging of oxygen-derived free radicals. They can interfere with few different free radical-producing systems, and can increase the function of the endogenous antioxidants. The aim of the research is to choose sources for the products with antioxidant activity from plants cultivated in Lithuania, evaluate quality and antioxidant activity of black currant, red currant and chokeberry products, to develop and evaluate technologies of phytopharmaceuticals with antioxidant activity... [to full text]

Objectives: To review, develop, and validate appropriate methods for quality control testing of sublingual (SL) tablets; to formulate and characterize new generations of SL tablets of epinephrine (E) for the potential first-aid treatment of anaphylaxis; and to evaluate the effects of non-medicinal ingredients (NMIs) on the in vitro characteristics and in vivo bioavailability of the formulated tablets. Methods: A custom-made apparatus and a novel method that simulates SL conditions were evaluated for dissolution testing of SL tablets. An electronic tongue (e-Tongue) was used to assess the degree of E bitterness and to demonstrate the masking effects of sweetening and/or flavoring agents. The effect of several NMIs in various properties on the in vitro characteristics of new generations of E SL tablets was evaluated. Formulations with the best in vitro characteristics, containing E 30 mg and 40 mg, were evaluated in vivo using our validated rabbit model and compared with placebo SL tablets (negative control) and E 0.3 mg intramuscular (IM) injection (positive control). Results: The novel in vitro dissolution testing resulted in accurate and reproducible data and was capable of detecting the effect of minor changes in formulations. Using the e-Tongue, E bitartrate had an extremely bitter taste which was masked to various degrees by the addition of aspartame, acesulfame potassium, and citric acid alone or in combination. Citric acid alone masked the bitter taste by >80%. The evaluation of NMIs revealed that the best formulation contained specific proportions of mannitol and coarse and fine grades of microcrystalline cellulose. Appropriate comparative testing resulted in the selection of a taste-masked E SL formulation with optimum in vitro characteristics. This formulation containing E 40 mg resulted in similar bioavailability to E 0.3 mg IM. This formulation containing E 30 mg had higher bioavailability than placebo, but lower bioavailability than E 40 mg tablets. Conclusions: Grades and proportions of NMIs carefully selected using appropriate in vitro testing resulted in successful formulations. The results of these in vitro tests enabled the development of the optimum E SL tablet formulation which was bioequivalent to the EpiPen. These tablets are potentially suitable for Phase 1 studies in humans and might transform the first-aid treatment of anaphylaxis in community settings.

Objectives: To review, develop, and validate appropriate methods for quality control testing of sublingual (SL) tablets; to formulate and characterize new generations of SL tablets of epinephrine (E) for the potential first-aid treatment of anaphylaxis; and to evaluate the effects of non-medicinal ingredients (NMIs) on the in vitro characteristics and in vivo bioavailability of the formulated tablets. Methods: A custom-made apparatus and a novel method that simulates SL conditions were evaluated for dissolution testing of SL tablets. An electronic tongue (e-Tongue) was used to assess the degree of E bitterness and to demonstrate the masking effects of sweetening and/or flavoring agents. The effect of several NMIs in various properties on the in vitro characteristics of new generations of E SL tablets was evaluated. Formulations with the best in vitro characteristics, containing E 30 mg and 40 mg, were evaluated in vivo using our validated rabbit model and compared with placebo SL tablets (negative control) and E 0.3 mg intramuscular (IM) injection (positive control). Results: The novel in vitro dissolution testing resulted in accurate and reproducible data and was capable of detecting the effect of minor changes in formulations. Using the e-Tongue, E bitartrate had an extremely bitter taste which was masked to various degrees by the addition of aspartame, acesulfame potassium, and citric acid alone or in combination. Citric acid alone masked the bitter taste by >80%. The evaluation of NMIs revealed that the best formulation contained specific proportions of mannitol and coarse and fine grades of microcrystalline cellulose. Appropriate comparative testing resulted in the selection of a taste-masked E SL formulation with optimum in vitro characteristics. This formulation containing E 40 mg resulted in similar bioavailability to E 0.3 mg IM. This formulation containing E 30 mg had higher bioavailability than placebo, but lower bioavailability than E 40 mg tablets. Conclusions: Grades and proportions of NMIs carefully selected using appropriate in vitro testing resulted in successful formulations. The results of these in vitro tests enabled the development of the optimum E SL tablet formulation which was bioequivalent to the EpiPen. These tablets are potentially suitable for Phase 1 studies in humans and might transform the first-aid treatment of anaphylaxis in community settings.