Thesis (Ph.D. (Pharmacy)) - Rhodes University, 2006.

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.

Aspen Pharmacare, one of the leading pharmaceutical manufacturers in South Africa has embarked on a programme of improving the production processes currently employed at their Port Elizabeth site. With the introduction of new technology at the site and the move towards globalization, it became imperative that Aspen remain competitive in the market. The product of interest in this research, Degoran Plus tablets, is one of the company’s leading brand sellers. Upon investigation, it became apparent that this product created opportunity for process improvement using the new technology. The manufacture of Degoran Plus entails granulation, compression and coating of the product. Most opportunity for improvement was possible in the granulation stage because of the laborious nature of the present process. Degoran Plus tablets had a history of analytical failures, especially with regard to the dissolution rate of the final product, as well as other quality related issues. The product was not considered to be a “through-runner”, which resulted in bad production output, due to continual repeats of not only analysis but also reworks in production. A strategic decision was taken to manufacture Degoran Plus using the Collette Gral granulator as the equipment offered superior mixing capability when compared to the Bear planetary granulator. It was assumed that the granulation process would result in more uniform distribution of the actives. Upon producing a better granule, a final product of superior quality would be attained. The validation protocol stipulates that three samples be taken and tested from the powder mix. Nine samples taken from granulated bulk are treated in the same manner. The validation protocol further stipulates that the first three batches manufactured utilise the new process, and tested according to the protocol. The results obtained from the analysis are evaluated statistically and a conclusion and recommendation were derived based on the evaluation.

Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of Pharmaceutical technology Consultant: PharmDr. Pavel Ondrejček, Ph.D. Student: Kateřina Vávrová Title of Thesis: Dissolution testing of tablets containing theophylline and mixtures of two types of calcium hydrogen phosphates and microcrystalline cellulose The aim of this thesis was the dissolution testing of tablets containing theophylline, the mixture of two dicalcium phosphate types and microcrystalline cellulose. The influence of tablet composition on the dissolution profiles was evaluated. The tablets were prepared from the mixtures containing microcrystalline cellulose, dicalcium phosphate anhydrous and dihydrate. These substances were used as fillers. Prepared mixtures contained theophylline as a model active ingredient and magnesium stearate as lubricant. Afterwards, the dissolution tests were done. For these tests, the basket method was utilized. As a dissolution medium the 0,1M hydrochloric acid solution was used. From the results of this experiment we concluded that we can influence the total amount of released theophylline and the speed of its release by the different ratio of microcrystalline cellulose and one of dicalcium phosphate types. The fastest theophylline dissolution was in tablets with high...

De digitala verktygen får allt mer plats i förskolans värld och det talas om att barn föds in i en digitaliserad värld. Syftet med denna undersökning var att få en inblick i hur man skulle kunna arbeta med lärplattan som ett pedagogiskt verktyg utifrån ett sociokulturellt perspektiv. För att kunna finna svar på våra frågor använde vi oss av en respondentundersökning. Vi gav oss ut och intervjuade tre IT-ansvariga och fem pedagoger på fyra förskolor. Resultatet visar att arbetet med lärplattan som ett pedagogiskt verktyg ser olika ut på de förskolor vi besökt, men att tanken bakom användandet av lärplattan ser lika ut. Det är betydelsefullt att pedagogerna i förskolan har ett syfte med lärplattan så att den inte blir en barnvakt.   Med detta arbete vill vi synliggöra hur arbetet med lärplattan som ett pedagogiskt verktyg kan se ut i praktiken. Vi har även under undersökningens gång mött på många användbara böcker som ger tips på hur man kan använda lärplattan som ett pedagogiskt verktyg, både i förskola och skola. Vi har därför valt att ge några boktips, dessa finns bifogade i bilagan boktips.

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Thesis supervisor: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Mgr. Pavel Ondrejček Student: Soňa Brtnová Title of Thesis: Evaluation of disintegration time of tablets containing theophylline The influence of used fillers on energetic profile of compression, especially influence on disintegration time of tablets with theophylline as a model drug, was studied in this thesis. Four tablet fillers were studied - microcrystalline cellulose Comprecel 102, lactose SpheroLac 100, calcium hydrogen phosphate anhydrous Di- Cafos A150 and calcium hydrogen phosphate dihydrate Di-Cafos D160. Tablets contained different proportion of two fillers, theophylline as a model drug and lubricant magnesium stearate. Tablets were compressed by the same compaction force 10 kN. The force- displacement record was evaluated using the particular energies of compaction process. Parameters of compaction process were influenced mostly by Comprecel 102. According to results there is no possibility to replace Di-Cafos D160 with Di-Cafos A150 in the mixtures. It was also found that SpheroLac 100 and Di-Cafos D160 shows similar behavior. Time of disintegration of tablets is mostly dependent on the used fillers. Tablets...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Hana Janoutová Title of Thesis: Evaluation of tensile strength of tablets containing theophylline The aim of this thesis was to determine tensile strength of tablets containing theophylline. Tensile strength was studied as a function of the composition of mixtures of the used fillers and especially on their ratio. In the theoretical part, the used materials - lactose SpheroLac 100, microcrystalline cellulose Comprecel 102, dibasic calcium phosphate dihydrate Di-Cafos D160, anhydrous dibasic calcium phosphate Di-Cafos A150, theophylline and magnesium stearate are described. This work also evaluates force-displacement record, tensile strength and various factors that affect tensile strength. Parameters of force-displacement record and tensile strength of the tablets compressed with compresssion force 10 kN were evaluated in the experimental part. The measured results show that higher values of precompression energy (E1) and energy of plastic deformation (E2) were detected in mixtures A, C and E which contain Comprecel 102, and the lowest values were detected in mixtures B which contain Sphero-Lac 100 and Di-Cafos D160. Values of energy...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Technology Consultant: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Andrea Matyášová Title of Thesis: Evaluation of compressibility of tableting mixtures containing theophylline using a compaction equation This thesis is aimed at the evaluation and comparison of excipients used in production of tablets. The compaction process of these excipients was evaluated using the parameters of the compaction equation. The mixtures of four fillers in various ratios were evaluated. These mixtures contained also theophylline as model drug and magnesium stearate as lubricant. The used three-exponential equation was previously developed by doc. RNDr. Milan Řehula, CSc. By using this compaction equation the volume reductions, speeds of volume reductions and consumed energies were calculated and evaluated. The results of this work showed that particular used fillers have different effect on the compaction process flow. That is caused primarily by different behavior of these materials during compaction and by formation of different types of bonds. Also the need of thorough cleaning and drying of compaction aid before compaction was confirmed.

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Consultant: Doc. PharmDr. Šklubalová Zdeňka, Ph.D. Student: Brunettová Monika Title of Thesis: Determination of flow properties of mixtures for preparation of tablets containing theophylline The aim of this diploma thesis was to characterize the flow properties and moisture content of mixtures for preparation of tablets containing theophylline. Parameters were monitored depending mainly on the content of the fillers, that were dicalcium phosphate, microcrystalline cellulose and lactose. Twenty-five prepared mixtures with different ratios of these fillers were evaluated. Flowability was evaluated by three methods stated in Czech Pharmacopoeia 2009 - compressibility index and Hausner ratio, flow through an orifice and angle of repose. Moisture content was evaluated as a weight loss during drying. Mixtures containing dicalcium phosphate and lactose proved more appropriate in terms of flowability, their flow properties are passable. However, according to the moisture content, mixture with microcrystalline cellulose are more preferable.

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Consultant: Doc. PharmDr. Sklubalova Zdenka, Ph.D. Student: Marketa Hofmanova Title of Thesis: Measurement of stress relaxation of mixtures of microcrystalline cellulose and calcium hydrogen phosphate intended for the preparation of tablets with theophylline The powder mixtures with theophylline were studied from the aspect of viscoelastic properties of used materials and tablets tensile strength. In the theoretical part the thesis concerned with description of materials which were used in the mixtures. They are: Microcrystalline cellulose Comprecel 102, calcium hydrogen phosphate anhydrate Di-Cafos A150, calcium hydrogen phosphate dihydrate Di-Cafos D160 and lactose SpheroLac 100. The thesis also deals with the stress relaxation test. The stress relaxation test, its evaluation by several methods and its use in the pharmacy and in different fields are described. The experimental part deals with viscoelastic characteristics of the mixtures. These characteristics were evaluated by stress relaxation test with maximal compression force 10 kN and dwell time 180 s. Also the tensile strength was evaluated. The highest values of parameters of elasticity A1-3 and plasticity P1-3 were measured in...