1 Abstract Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Consultant: Assoc. Prof. PharmDr. Zdenka Sklubalova, Ph.D. Student: Viktoria Kousoulidou Title of Thesis: Determination of the compressibility of excipients used for formulation of tablets with theophylline The current thesis is focused on the compressibility properties of five powders used in tablet formulation: Comprecel, Spherolac, DI-CAFOS D160, DI-CAFOS A150 as excipients and Theophylline as the active substance. The particle size, moisture content, bulk density and flowability of the powders are determined. The powders are compressed and the results are evaluated by means of the parameters of the compaction equation and the force-displacement method (compression under 5, 10, 15 kN). Then, the crushing strength of tablets prepared from each powder by the force-displacement method is measured. The average values of the crushing strength are used to calculate the tensile strength of the tablets. Best compressibility is found in Comprecel and Theophylline with tensile strength values of 1.31 MPa under 5 kN, 3.31 MPa under 10 kN, 4.75 MPa under 15 kN and 1.02 MPa under 5 kN, 2.27 MPa under 10 kN, 3.09 MPa under 15 kN, respectively.

A ampicilina é um antibiótico semi-sintético, derivado da penicilina, que exibe amplo espectro de ação, sendo largamente comercializada no Brasil, onde são encontrados cerca de doze produtos sob a forma de comprimidos. O presente trabalho teve como propósito avaliar, do ponto de vista biofarmacêutico, quatro marcas comerciais (A, B, C e D) de comprimidos de ampicilina 500 mg, sendo que, para um dos laboratórios foram analisados dois lotes diferentes (AI e A2). Foram executadas análises físicas e físico-químicas in vitro (aspecto, variação de peso, diâmetro, espessura e dureza, friabilidade, tempo de desagregação, teste e perfil de dissolução e teor de ampicilina), com a finalidade de detectar-se possíveis falhas em relação a formulação e/ou tecnologia utilizada na fabricação dos produtos. Executou-se, também, um estudo de bioequivalência entre as formulações A2 e B, a fim de se verificar se ambas podem ser consideradas intercambiáveis. Para tanto, realizou-se um estudo cruzado aleatório em dois períodos, utilizando-se dezesseis voluntários sadios, sendo o fármaco quantificado na urina pelo método espectrofotométrico descrito inicialmente por SMITH et al. (1967). Os parâmetros farmacocinéticos avaliados foram a quantidade total de ampicilina excretada na urina (Du∞) e a velocidade máxima de excreção [(dDu/dt)max]. Os resultados das análises físicas e físico-químicas indicaram que o produto A1 apresentou diversas falhas, sendo estas constatadas, também, para C e D. Ao contrário, A2 e B não registraram qualquer discrepância. Na avaliação da bioequivalência entre as formulações A2 e B, obteve-se um intervalo de confiança de 93 a 110% para Du∞ e 91 a 132% para (dDu/dt)max. De acordo com as normas internacionalmente aceitas é possível concluir que as formulações podem ser consideradas bioequivalentes e, portanto, intercambiáveis. / Ampicillin is a semi-synthetic penicillin-derived antibiotic that has a broad action spectrum. In Brazil, where it is largely marketed, about twelve different tablets brands can be found. The aim of the present work was to evaluate from the biopharmaceutic point of view four ampicillin 500mg-tablet brands (A, B, C and D). Two different A-brand lots (AI and A2) were analyzed. Physical and in vitro physical-chemical analysis (aspect, weight variation, diameter, thickness and hardness, friability, disintegration time, dissolution test and profile and ampicillin content) were carried out in order to detect possible manufacturing failures as to formulation and/or technology used. A bioequivalence study between A2 and B was also carried out in order to check if both of them could be interchangeable. For such an aleatory two-period cross-over study was done by quantifying through spectrophotometry (SMITH et al., 1967) the content of ampicillin in sixteen healthy volunteers\'urine. The total ampicillin amount excreted in urine (Du∞) and maximum rate of excretion [(dDu/dt)max] were taken as pharmacokinetics parameters. The physical and physical-chemical analyses results indicated critical failures in A1 brand. Similarly several failures were also detected in C and D. Brands A2 and B instead showed no discrepancies. Confidence intervals of 93 to 110% for Du∞ and 91 to 132% for (dDu/dt)max, were found through bioequivalence evaluation between A2 and B formulations. According to international accepted standards both the fomulations can be considered bioequivalent, therefore interchangeable.

O ibuprofeno é um anti-inflamatório não-esteroidal (AINE) que possui propriedades analgésicas e anti-térmicas e é empregado na terapêutica em casos dores discretas e moderadas, artrite reumatóide, osteoartrite e dismenorréia primária, nas concentrações de 200, 300, 400 e 600 mg. Entretanto, a formulação contendo 200 mg não está disponível no mercado farmacêutico brasileiro. No presente trabalho, foi desenvolvida uma formulação de comprimidos de ibuprofeno 200 mg que apresentou, além de outras características físico-químicas adequadas, um ótimo perfil de dissolução. Foram testadas oito formulações, obtidas a partir de um projeto fatorial fracionado, avaliando-se diversos excipientes. Além disto, as formulações foram submetidas à temperatura ambiente, 37 ºC e 50 ºC, e analisadas à 30 e 60 dias, com o objetivo de avaliar as transformações físicas que podem ocorrer durante o armazenamento das mesmas. Os resultados das análises físico-químicas foram tratados estatisticamente, utilizando-se o programa STATGRAFCS, através de uma análise exploratória e de um estudo de efeitos. Concluiu-se, então, que a melhor formulação foi a seguinte: IBUPROFENO - 200; AMIDO - 47; LACTOSE - 72; CELULOSE MICROCRISTALINA - 23; ESTEARATO DE MAGNESIO - 8. / Ibuprofen is a non steroidal antiinflamatory drug (NSAD), that has analgesic and antipyretic properties. It is used in terapeutic cases of mild to moderant pain, rheumatoid arthritis, osteoarthritis, and primary dysmenorrhea, in the 200, 300, 400, and 600 mg of concentration. In the Brazilian pharmaceutical market the formulation of 200 mg doesn\'t exist. In this study, a formulation of ibuprofen was developed for 200 mg tablets, that has suitable physical-chemical properties and an excellent dissolution profile. The eight formulations tested were obtained from factorial designs, evaluating several excipients. These formulations also had been submitted at room temperature, 37 ºC, and 50 ºC and were analised at 30 and 60 days, with the objective to evaluate the physical transformatiom that could have occurred during that time. The results were tested statistically by the STATGRAFCS program, using the exploratory analysis and the effects study. The final results showed that the best formulation was: IBUPROFEN - 200; STARCH - 47; LACTOSE - 72; MICROCRYSTALLINE CELLULOSE - 23; MAGNESIUM STEARATE - 8.

O ibuprofeno é um anti-inflamatório não-esteroidal (AINE) que possui propriedades analgésicas e anti-térmicas e é empregado na terapêutica em casos dores discretas e moderadas, artrite reumatóide, osteoartrite e dismenorréia primária, nas concentrações de 200, 300, 400 e 600 mg. Entretanto, a formulação contendo 200 mg não está disponível no mercado farmacêutico brasileiro. No presente trabalho, foi desenvolvida uma formulação de comprimidos de ibuprofeno 200 mg que apresentou, além de outras características físico-químicas adequadas, um ótimo perfil de dissolução. Foram testadas oito formulações, obtidas a partir de um projeto fatorial fracionado, avaliando-se diversos excipientes. Além disto, as formulações foram submetidas à temperatura ambiente, 37 ºC e 50 ºC, e analisadas à 30 e 60 dias, com o objetivo de avaliar as transformações físicas que podem ocorrer durante o armazenamento das mesmas. Os resultados das análises físico-químicas foram tratados estatisticamente, utilizando-se o programa STATGRAFCS, através de uma análise exploratória e de um estudo de efeitos. Concluiu-se, então, que a melhor formulação foi a seguinte: IBUPROFENO - 200; AMIDO - 47; LACTOSE - 72; CELULOSE MICROCRISTALINA - 23; ESTEARATO DE MAGNESIO - 8. / Ibuprofen is a non steroidal antiinflamatory drug (NSAD), that has analgesic and antipyretic properties. It is used in terapeutic cases of mild to moderant pain, rheumatoid arthritis, osteoarthritis, and primary dysmenorrhea, in the 200, 300, 400, and 600 mg of concentration. In the Brazilian pharmaceutical market the formulation of 200 mg doesn\'t exist. In this study, a formulation of ibuprofen was developed for 200 mg tablets, that has suitable physical-chemical properties and an excellent dissolution profile. The eight formulations tested were obtained from factorial designs, evaluating several excipients. These formulations also had been submitted at room temperature, 37 ºC, and 50 ºC and were analised at 30 and 60 days, with the objective to evaluate the physical transformatiom that could have occurred during that time. The results were tested statistically by the STATGRAFCS program, using the exploratory analysis and the effects study. The final results showed that the best formulation was: IBUPROFEN - 200; STARCH - 47; LACTOSE - 72; MICROCRYSTALLINE CELLULOSE - 23; MAGNESIUM STEARATE - 8.

Inaug.-diss.--Leipzig. / Comprises the phonology only; the complete treatise, including the text of the Greek inscription on the Heraclean tablets, was published in "Studien zur griechischen und lateinischen grammatik, hrsg. von Georg Curtius", v. 4, 1871, p. [355]-469.

Summary The aim of the study was to obtain multiparticulate prolonged release drug delivery systems by incorporating microgranules with selegiline hydrochloride (SCh) and pellets with verapamil hydrochloride (VH) into lyophilized and pressed tablets, respectively. Also it was assumed to preserve primary dosage form properties unchanged in final drug form. Prolonged drug action is very important nowadays because using these drug forms, a drug plasma level is more constant, which is associated with less adverse side-effects, a more constant and prolonged therapeutic effect and a better compliancy. In the study all the batches of microgranules (XPS1, XPS3 and XPS3P) were prepared by cross-linking the pectin with Zn2+ ions. During this process the active pharmaceutical ingredient (SCh) was incorporated in the cross-linked granules (SCh to pectin ratio was 1:2). In this case namely cross-linking the pectin with Zn ions has the main influence in gaining drug prolonged release properties. In order to evaluate, how the coating can change microgranule properties, they were additionally coated with 2% pectin solution (XPS3P). Selegiline has an extensive presystemic metabolism resulting in inadequate oral absorption (absolute bioavailability is only about 10%), there is a need for developing a new drug delivery systems, which provide higher drug concentration in the blood. As an alternative to conventional oral forms and injections, boccoadhesive therapeutic agents can be used. Direct... [to full text] / Magistrinio darbo tikslas buvo pagaminti multirezervuarinio tipo prailginto poveikio vaistines formas inkorporuojant mikrogranules su selegilino hidrochloridu (SCh) bei peletes su verapamilio hidrochloridu (VH) atitinkamai į liofilizuotas ir presuotas tabletes. Taip pat buvo siekiama išlaikyti pirmines tarpinių formų (mikrogranulių bei pelečių) savybes galutinėse vaistų formose (liofilizuotose tabletėse bei įprastose presuotose tabletėse). Prailgintas vaisto poveikis šiuo metu yra labai aktualus, nes vartojant tokį vaistą didėja gydytojo-paciento susitarimo laikymasis (pacientui vaistą vartoti vieną kartą per dieną yra žymiai patogiau nei keliskart ). Mokslinio darbo metu visos mikrogranulių partijos (XPS1, XPS3 ir XPS3P) buvo gaminamos modifikuotos drėgnosios granuliacijos būdu surišant pektiną dvivalenčio cinko jonais. Būtent šis procesas turėjo lemiamą įtaką prailginto vaisto poveikio gavimui. Į sujungtą pektiną vaistinė medžiaga (SCh) buvo įvestas dviem būdais: miltelių ir 20% tirpalo forma. Gautos mikrogranulės susmulkintos kavamale ir iš jų atskirta 100 - 200 µm frakcija, kuri ir buvo panaudota tolimesniam tyrimui. Norint įvertinti avalkalo įtaką vaistinės medžiagos atsipalaidavimui, mikrogranulės buvo papildomai padengtos 2% pektino tirpalu. Veiklioji medžiaga SCh organizme gausiai metabolizuojama kepenyse, todėl vartojimas per os nėra efektyvus (absoliutus bioprieinamaumas yra tik 10%). Kaip alternatyva injekcinėms formoms gali būti mukoadhezinės, skirtos aplikuoti... [toliau žr. visą tekstą]

The aim of this thesis is to study preschool-teachers’ experiences from using the computer tablet as a tool for learning and teaching, in order to gain knowledge of how the integrational process of information and communications technology (ICT) in preschool has progressed since its instatement. The background that caused interest to make this study was the rapid progression of the use of ICT-tools in childrens’ everyday lives and the troubles that have surrounded the process of integrating these tools into preschool-practices. The theoretical basis for the analysis of the research lies within the socio-cultural perspective. The methods used to gather empirical data were discussions held in focus-groups consisting of teachers from three different preschools in Sweden where the theme of the discussions were computer tablets. In accordance with a socio-cultural approach to verbal communication as data the discussions were seen as socially situated practices. The results of this study were that tablets were only in part integrated with school-activities as they were well used for by the pedagogues for purposes such as organizing, documentation and communication but not as well used among the children due to different circumstances. Another finding of the study was that teachers find that they often lack the ICT-competences required to develop good learning situations and conditions for their students with the computer tablets. Based on the teachers’ testimonies not only is there a need for in-service training for teachers but perhaps also necessary to provide teachers with further direction for work with computer tablets, how they should be used and the extent of their role within preschool settings.

No description available.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Chemical and Biochemical Engineering." Includes bibliographical references.